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| Name | Class |
|---|---|
| DuPont Nutrition and Health | INDUSTRY |
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The aim of this study is to assess whether a 5 week intake of a probiotic (Lpc-37) can modulate stress and anxiety experienced by healthy subjects during and after an acute stressor compared to placebo. To measure stress and anxiety, markers of the hypothalamic-pituitary-adrenal (HPA) axis activity and questionnaires will be assessed before, during and after the Trier Social Stress Test (TSST). The results of this study indicate if the chosen study design is suitable to discover stress-related effects of probiotics.
The total mass of microorganisms residing within the human intestine is approximately the same as that of the human brain. Of late, these >1000 species and >7000 strains have been described as the "brain in our belly" because of the essential role they play in physiological and psychological health and disease. The gut-brain axis describes the bidirectional communication that exists between the brain and the gut and the microbiota-gut-brain axis supports the role of the gut microbiome in this communication system. Emotional and routine daily life stress can disrupt digestive function, but increasing evidence indicates that the gut microbiota exert a profound influence on brain physiology, psychological responses and ultimately behavior.
A plethora of literature to date, albeit predominantly preclinical, have demonstrated evidence to support the role of the gut microbiome in regulating stress-related changes in physiology, behavior and brain function.
Stress is an individual process to deal with external and internal challenges that ranges from behavioral to molecular adaptations. The HPA axis and its release of stress hormones plays a major role in stress adaptation.
The purpose of this clinical trial is to determine whether a single strain of bacteria derived from the species Lacticaseibacillus paracasei Lpc-37 (Lpc-37), formerly Lactobacillus paracasei Lpc-37, can modulate stress experienced by healthy subjects exposed to the TSST measured by HPA axis activation markers and self-report questionnaires.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lpc-37 | Active Comparator | Lacticaseibacillus paracasei Lpc-37 (Lpc-37), formerly Lactobacillus paracasei Lpc-37 1x 1 capsule in the morning for 5 weeks |
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| Placebo | Placebo Comparator | Placebo capsule manufactured to mimic Lpc-37 capsule 1x 1 capsule in the morning for 5 weeks |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lpc-37 | Dietary Supplement | Lacticaseibacillus paracasei Lpc-37 at 1.75 x 10^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide |
| Measure | Description | Time Frame |
|---|---|---|
| Change of the Heart Rate (HR) in Response to the Trier Social Stress Test (TSST) | Efficacy was defined as a lower increase in HR in response to the TSST following intervention with Lpc-37, compared to placebo. | Continuous measurement starting 20 minutes before and ending 20 minutes after the TSST after 5 weeks of product intake. Mean values were calculated per group at seven-time windows before, during and after the TSST |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in Pre and Post Treatment STAI-state Scores | Efficacy of the intake of Lpc-37 on the reduction of State-Trait-Anxiety-Inventory (STAI)-state scores compared to placebo. Measured with the german version of the State-Trait-Anxiety Inventory, scale anxiety as a temporary emotional state (STAI-X1). Answers are given on a four-point rating scale ranging from 1="not at all" to 4="very true". The score range is 20-80; Higher scores indicate more anxiety. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Juliane Hellhammer, PhD | Daacro GmbH & Co. KG | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| daacro GmbH & Co. KG | Trier | Rhineland-Palatinate | 54296 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 10461128 | Background | Bailey MT, Coe CL. Maternal separation disrupts the integrity of the intestinal microflora in infant rhesus monkeys. Dev Psychobiol. 1999 Sep;35(2):146-55. | |
| 21040780 | Background | Bailey MT, Dowd SE, Galley JD, Hufnagle AR, Allen RG, Lyte M. Exposure to a social stressor alters the structure of the intestinal microbiota: implications for stressor-induced immunomodulation. Brain Behav Immun. 2011 Mar;25(3):397-407. doi: 10.1016/j.bbi.2010.10.023. Epub 2010 Oct 30. |
| Label | URL |
|---|---|
| daacro homepage | View source |
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Of 176 eligible participants, 120 met inclusion criteria and were enrolled in the study between April and October 2018.
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| ID | Title | Description |
|---|---|---|
| FG000 | Lpc-37 | Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the Investigational Product (IP) every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS). |
| FG001 | Placebo | Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the Investigational Product (IP) every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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120 participants met the inclusion/exlusion criteria and were enrolled in the study. Two participants were excluded during the run-in period (use of antibiotics and withdrawn consent) and one participant withdrew consent during the intervention period.
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| ID | Title | Description |
|---|---|---|
| BG000 | Lpc-37 | Verum: Lacticaseibacillus paracasei Lpc-37 (Lpc-37) Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS). |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change of the Heart Rate (HR) in Response to the Trier Social Stress Test (TSST) | Efficacy was defined as a lower increase in HR in response to the TSST following intervention with Lpc-37, compared to placebo. | PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies). | Posted | Mean | Standard Deviation | bpm | Continuous measurement starting 20 minutes before and ending 20 minutes after the TSST after 5 weeks of product intake. Mean values were calculated per group at seven-time windows before, during and after the TSST |
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Adverse event (AE) data was collected daily during the 5-week intervention period and tracked when the AE continued at the end of the study (up to 30 days afterwards)
AE reporting was done by the Investigator or her designees. All AEs were collected on the paper case report forms.
Variables recorded for each AE: Description of the event, onset and resolution (date and time), whether the AE is ongoing at the end of the study, intensity (mild, moderate, severe), therapy of event, action taken, outcome, causality (definitely, probably, possibly, unlikely, not related, not assessable) and whether it constitutes an Serious Adverse Event (SAE) or not.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Lpc-37 | Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| common cold | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Elaine Patterson, Ph. D. | DuPont Nutrition and Biosciences | +358-40-4827-626 | elaine.patterson@dupont.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 14, 2018 | Oct 27, 2020 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D013315 | Stress, Psychological |
| D001008 | Anxiety Disorders |
| ID | Term |
|---|---|
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
| D001523 | Mental Disorders |
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| Placebo | Dietary Supplement | microcrystalline cellulose, magnesium stearate, silicon dioxide |
|
| Before and after 5 weeks of study product intake. |
| Changes in Pre and Post Treatment Perceived Stress Scale (PSS) Scores | Efficacy of the intake of Lpc-37 on the reduction of Perceived Stress Scale (PSS) scores compared to placebo. Measured with the german version of the PSS as a psychological instrument for measuring stress perception. It assesses how unpredictable, uncontrollable and overloaded participants perceived their lives to have been within the last month. The PSS comprises 14 items that are answered on a five-point rating scale ranging from 0 = "never" to 4 = "very often". Individual scores on the PSS can range from 0 to 56 with higher scores indicating higher perceived stress. | Before and after 5 weeks of study product intake. |
| Changes in Pre and Post Treatment DASS Depression Scores | Efficacy of the intake of Lpc-37 on the reduction of Depression Anxiety Stress Scale (DASS) depression scores compared to placebo. Measured with the german version of the DASS as a 42-item self report instrument designed to measure negative emotional states of depression, anxiety and stress during the past week. The DASS includes three scales (depression, anxiety and stress) of which each scale includes 14 items that are divided into subscales of 2-5 items of similar content. Items are answered on a four point rating scale ranging from 0 = "not at all" to 3 = "very much". Scores of each scale are calculated by summing the scores for the relevant items. The Depression scale assesses dysphoria, hopelessness, devaluation of life, self-deprecation, lack of interest/involvement, anhedonia, and inertia. The items are 3, 5, 10, 13, 16, 17, 21, 24, 26, 31, 34, 37, 38, 42 and individual scores can range from 0 to 42 with higher scores indicating greater severity of the symptoms. | Before and after 5 weeks of study product intake. |
| Changes in Pre and Post Treatment DASS Anxiety Scores | Efficacy of the intake of Lpc-37 on the reduction of Depression Anxiety Stress Scale (DASS) anxiety scores compared to placebo. Measured with the german version of the DASS as a 42-item self report instrument designed to measure negative emotional states of depression, anxiety and stress during the past week. The DASS includes three scales (depression, anxiety and stress) of which each scale includes 14 items that are divided into subscales of 2-5 items of similar content. Items are answered on a four point rating scale ranging from 0 = "not at all" to 3 = "very much". Scores of each scale are calculated by summing the scores for the relevant items. The anxiety scale assesses autonomic arousal, skeletal muscle effects, situational anxiety, and subjective experience of anxious affect. The items are 2, 4, 7, 9, 15, 19, 20, 23, 25, 28, 30, 36, 40, 41 and individual scores can range from 0 to 42 with higher scores indicating greater severity of the symptoms. | Before and after 5 weeks of study product intake. |
| Changes in Pre and Post Treatment DASS Stress Scores | Efficacy of the intake of Lpc-37 on the reduction of Depression Anxiety Stress Scale (DASS) stress scores compared to placebo. Measured with the german version of the DASS as a 42-item self report instrument designed to measure negative emotional states of depression, anxiety and stress during the past week. The DASS includes three scales (depression, anxiety and stress) of which each scale includes 14 items that are divided into subscales of 2-5 items of similar content. Items are answered on a four point rating scale ranging from 0 = "not at all" to 3 = "very much". Scores of each scale are calculated by summing the scores for the relevant items. The stress scale (items) is sensitive to levels of chronic non-specific arousal.The stress scale items are 1, 6, 8, 11, 12, 14, 18, 22, 27, 29, 32, 33, 35, 39 and individual scores can range from 0 to 42 with higher scores indicating greater severity of the symptoms. | Before and after 5 weeks of study product intake. |
| Changes in Pre and Post Treatment BAI Scores | Efficacy of the intake of Lpc-37 on the reduction of Beck Anxiety Inventory (BAI) scores compared to placebo. Measured with the german version of the Beck Anxiety Inventory as a self-rating scale designed to measure anxiety. It comprises 21 sentences describing feelings that can occur when being anxious. These sentences are rated on a four-point rating scale ranging from 0="not at all" to 3="severely", considering the last 7 days. The score range is 0-63; Higher scores indicate higher anxiety. | Before and after 5 weeks of study product intake. |
| Changes in Pre and Post Treatment VAS Stress Perception Scores | Efficacy of the intake of Lpc-37 on the reduction of Visual Analog Scale (VAS) stress perception scores compared to placebo. Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating higher perceived stress. | Before and after 5 weeks of study product intake. |
| Changes in Pre and Post Treatment VAS Anxiety Scores | Efficacy of the intake of Lpc-37 on the reduction of VAS anxiety scores compared to placebo. Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater anxiety. | Before and after 5 weeks of study product intake. |
| Changes in Pre and Post Treatment VAS Insecurity Scores | Efficacy of the intake of Lpc-37 on the reduction of VAS insecurity scores compared to placebo. Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater insecurity. | Before and after 5 weeks of study product intake. |
| Changes in Pre and Post Treatment VAS Exhaustion Scores | Efficacy of the intake of Lpc-37 on the reduction of VAS exhaustion scores compared to placebo. Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater exhaustion. | Before and after 5 weeks of study product intake. |
| Changes in Pre and Post Treatment Systolic BP | Efficacy of the intake of Lpc-37 on the reduction of systolic blood pressure (BP). | Before and after 5 weeks of study product intake. |
| Changes in Pre and Post Treatment Diastolic BP | Efficacy of the intake of Lpc-37 on the reduction of diastolic BP. | Before and after 5 weeks of study product intake. |
| Change of STAI-State Scores in Response to the TSST | Efficacy of the intake of Lpc-37 on reduction of the increase of STAI-State scores in response to the TSST compared to placebo. Measured with the german version of the State-Trait-Anxiety Inventory, scale anxiety as a temporary emotional state (STAI-X1). Answers are given on a four-point rating scale ranging from 1="not at all" to 4="very true". The score range is 20-80; Higher scores indicate more anxiety. | 10 minutes before the TSST and 1 minute after the TSST after 5 weeks of study product intake |
| Change of Systolic BP in Response to the TSST | Efficacy of the intake of Lpc-37 on reduction of the increase of the systolic BP in response to the TSST compared to placebo. | 3 minutes before the TSST and 1 minute after the TSST after 5 weeks of study product intake |
| Change of Diastolic Blood Pressure (BP) in Response to the TSST | Efficacy of the intake of Lpc-37 on reduction of the increase of the diastolic BP in response to the TSST compared to placebo. | 3 minutes before the TSST and 1 minute after the TSST after 5 weeks of study product intake |
| Change of VAS Stress Perception Scores in Response to the TSST | Efficacy of the intake of Lpc-37 on reduction of the increase of VAS Stress perception scores in response to the TSST compared to placebo. Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating higher perceived stress. | 10 minutes before the TSST, during the TSST and 1 minute after the TSST after 5 weeks of study product intake |
| Change of VAS Anxiety Scores in Response to the TSST | Efficacy of the intake of Lpc-37 on reduction of the increase of VAS anxiety scores in response to the TSST compared to placebo. Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater anxiety. | 10 minutes before the TSST, during the TSST and 1 minute after the TSST after 5 weeks of study product intake |
| Change of VAS Insecurity Scores in Response to the TSST | Efficacy of the intake of Lpc-37 on reduction of the increase of VAS insecurity scores in response to the TSST compared to placebo. Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater insecurity. | 10 minutes before the TSST, during the TSST and 1 minute after the TSST after 5 weeks of study product intake |
| Change of VAS Exhaustion Scores in Response to the TSST | Efficacy of the intake of Lpc-37 on reduction of the increase of VAS exhaustion scores in response to the TSST compared to placebo. Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater exhaustion. | 10 minutes before the TSST, during the TSST and 1 minute after the TSST after 5 weeks of study product intake |
| Change of Salivary Cortisol in Response to the TSST | Efficacy of the intake of Lpc-37 on reduction of the increase of salivary cortisol in response to the TSST compared to placebo. | 1 minute before the TSST and 1, 10, 20, 30 and 45 minutes after the TSST after 5 weeks of study product intake |
| Change of sAA in Response to the TSST | Efficacy of the intake of Lpc-37 on reduction of the increase of salivary Alpha-Amylase (sAA) in response to the TSST compared to placebo. | 1 minute before the TSST and 1, 10, 20, 30 and 45 minutes after the TSST after 5 weeks of study product intake |
| Change of Sleep Duration Over the Course of the Treatment | Efficacy of the intake of Lpc-37 on the increase of sleep duration over the course of the treatment. Sleep duration was monitored through the wash-out phase (week 1 and 2) and the subsequent treatment phase (weeks 3-7). Efficacy is defined as an increase, or (in case of a general decrease) reduced decrease for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one value for each day and participant. Summary measures for Sleep duration for the averaged ratings per participant and week | Daily for 2 weeks before treatment intake and 5 weeks during treatment intake |
| Change of Sleep Related Recovery Scores Over the Course of the Treatment | Efficacy of the intake of Lpc-37 on the increase of sleep related recovery scores over the course of the treatment. Measured with a daily online diary. Sleep related recovery was rated by participants on an 11-point scale (0-10; "not at all" to "very") and monitored throughout the wash-out phase (Week 1 and 2) and the subsequent treatment phase (weeks 3-7). High scores indicate a high recovery. Efficacy is defined as an increase, or (in case of a general decrease) reduced decrease for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one value for each day and participant. Summary measures for sleep related recovery for the averaged ratings per participant and week. | Daily for 2 weeks before treatment intake and 5 weeks during treatment intake |
| Change of Reported Sleep Disruptions Over the Course of the Treatment by Week (Proportion Yes/Total) | Efficacy of the intake of Lpc-37 on the decrease of sleep disruptions over the course of the treatment measured with a daily online diary (Proportion (yes/total)). Sleep disruptions were monitored through the wash-out phase and the subsequent treatment phase for each week. In the binary version, the value is either Yes or No for each day and each participant. Efficacy is defined as a decrease, or (in case of a general increase) reduced increase for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one value for each day and participant. The proportion of participants with at least one sleep disruption by treatment group is given, treatment commenced after week 2. Data listed here reflect the proportion of participants who answered "Yes" (e.g. 0,477 * 44 = 20.99 participants answered with "Yes" in week 1 in the Lpc-37 group). | Daily for 2 weeks before treatment intake and 5 weeks during treatment intake |
| Change of Reported Number of Sleep Disruptions Over the Course of the Treatment | Efficacy of the intake of Lpc-37 on the decrease of reported number of sleep disruptions over the course of the treatment measured with a daily online diary (mean of week summary). Sleep disruptions were monitored through the wash-out phase (Week 1 and 2) and the subsequent treatment phase (Weeks 3-7). In the count version, the value can be 0 or a natural number for each day and each participant. Efficacy is defined as a decrease, or (in case of a general increase) reduced increase for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one value for each day and participant. Values reflect summary measures for sleep disruptions (count) for the summed counts per participant and week. | Daily for 2 weeks before treatment intake and 5 weeks during treatment intake |
| Change of Perceived Health Status Scores Over the Course of the Treatment | Efficacy of the intake of Lpc-37 on the increase of perceived health status scores over the course of the treatment. Measured with a daily online diary. Health status was rated by participants on an 11-point scale (0-10; "not at all" to "very") and monitored through the wash-out phase (week 1 and 2) and the subsequent treatment phase (weeks 3-7). Higher scores indicate a high perceived health.Efficacy is defined as an increase, or (in case of a general decrease) reduced decrease for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one value for each day and participant. Values reflect summary measures for perceived health status on a scale from 0 to 10 for the averaged ratings per participant and week. | Daily for 2 weeks before treatment intake and 5 weeks during treatment intake |
| Change of Mood Scale Scores Over the Course of the Treatment | Efficacy of the intake of Lpc-37 on the increase of mood scale scores over the course of the treatment Measured with a daily online diary. Mood was rated by participants on an 11-point scale (0-10; "very bad" to "very well") and monitored through the washout phase (week 1 and 2) and the subsequent treatment phase (weeks 3-7). Higher scores indicate a better mood. Efficacy is defined as an increase, or (in case of a general decrease) reduced decrease for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one average value for each week and participant. Values reflect summary measures for mood ratings on a scale from 0 to 10 for the averaged ratings per participant and week. | Daily for 2 weeks before treatment intake and 5 weeks during treatment intake |
| Change of Perceived Productivity Scores Over the Course of the Treatment | Efficacy of the intake of Lpc-37 on the increase of perceived productivity scores over the course of the treatment Measured with a daily online diary. Productivity was rated by participants on an 11-point scale (0-10; "not at all" to "very") and monitored through the wash-out phase (week 1 and 2) and the subsequent treatment phase (weeks 3-7). Higher scores indicate a higher perceived productivity. Efficacy is defined as an increase, or (in case of a general decrease) reduced decrease for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group.Time is coded as a continuous variable with one value for each day and participant. The values reflect summary measures for perceived productivity on a scale from 0 to 10 for the averaged ratings per participant and week. | Daily for 2 weeks before treatment intake and 5 weeks during treatment intake |
| The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of CAR AUCg Measures | Efficacy of the intake of Lpc-37 on the reduction of the difference of Cortisol Awakening Response (CAR) area under the curve with respect to the ground (AUCg) values to the respective mean before and after 5 weeks of treatment. The CAR is summarized in the variables AUCg, AUCi, mean increase and peak value. These cortisol indices are frequently used to describe hypothalamic-pituitary-adrenal axis activity and represent information either of the total cortisol production or of the change in cortisol levels. AUCg is the total area under the curve of all measurements (i.e., the intensity or magnitude of the response). Efficacy for the CAR variables AUCg is defined in terms of a normalization: Number of participants with normal values (between first and third quantile of reference measures) and numbers of participants with low or high values are compared before treatment and after treatment. More participants in the normal range after treatment is defined as efficacy. | Baseline (average of 2 days before first product intake) and end of study (average of 2 days before last product intake) |
| The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of Cortisol Awakening Response (CAR) AUCi Measures | Efficacy of the intake of Lpc-37 on the reduction of the difference of CAR area under the curve with respect to the increase (AUCi) values to the respective mean before and after the treatment. The CAR is summarized in the variables AUCg, AUCi, mean increase and peak value. These cortisol indices are frequently used to describe hypothalamic-pituitary-adrenal axis activity and represent information either of the total cortisol production or of the change in cortisol levels. AUCi is calculated with reference to the baseline measurement and it ignores the distance from zero for all measurements and emphasizes the changes over time. Efficacy for the CAR variables AUCi is defined in terms of a normalization: Number of participants with normal values (between first and third quantile of reference measures) and numbers of participants with low or high values are compared before treatment and after treatment. More participants in the normal range after treatment is defined as efficacy. | Baseline (average of 2 days before first product intake) and end of study (average of 2 days before last product intake) |
| The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of Cortisol at Awakening Measures | Efficacy of the intake of Lpc-37 on the reduction of the difference of Cortisol at Awakening values to the respective mean before and after 5 weeks of treatment Efficacy for the CAR variable cortisol at awakening is defined in terms of a normalization: Number of participants with normal values (between first and third quantile of reference measures) and numbers of participants with low or high values are compared before treatment and after treatment. More participants in the normal range after treatment is defined as efficacy. | Baseline (average of 2 days before first product intake) and end of study (average of 2 days before last product intake) |
| The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of CAR 8pm Measures | Efficacy of the intake of Lpc-37 on the reduction of the difference of cortisol at 8 pm values to the respective mean before and after 5 weeks of treatment Efficacy for the CAR variable cortisol at 8 pm is defined in terms of a normalization: Number of participants with normal values (between first and third quantile of reference measures) and numbers of participants with low or high values are compared before treatment and after treatment. More participants in the normal range after treatment is defined as efficacy. | Baseline (average of 2 days before first product intake) and end of study (average of 2 days before last product intake |
| 15085020 | Background | Bailey MT, Lubach GR, Coe CL. Prenatal stress alters bacterial colonization of the gut in infant monkeys. J Pediatr Gastroenterol Nutr. 2004 Apr;38(4):414-21. doi: 10.1097/00005176-200404000-00009. |
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| 33385020 | Derived | Patterson E, Griffin SM, Ibarra A, Ellsiepen E, Hellhammer J. Lacticaseibacillus paracasei Lpc-37(R) improves psychological and physiological markers of stress and anxiety in healthy adults: a randomized, double-blind, placebo-controlled and parallel clinical trial (the Sisu study). Neurobiol Stress. 2020 Nov 24;13:100277. doi: 10.1016/j.ynstr.2020.100277. eCollection 2020 Nov. |
| BG001 | Placebo | Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS). |
| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Weight | Mean | Standard Deviation | kg |
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| Height | Mean | Standard Deviation | cm |
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| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m² |
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| Systolic blood pressure (BP) | Mean | Standard Deviation | mmHg |
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| Diastolic blood pressure (BP) | Mean | Standard Deviation | mmHg |
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| Heart rate | Mean | Standard Deviation | bpm |
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| OG001 | Placebo | Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups. |
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| Secondary | Changes in Pre and Post Treatment STAI-state Scores | Efficacy of the intake of Lpc-37 on the reduction of State-Trait-Anxiety-Inventory (STAI)-state scores compared to placebo. Measured with the german version of the State-Trait-Anxiety Inventory, scale anxiety as a temporary emotional state (STAI-X1). Answers are given on a four-point rating scale ranging from 1="not at all" to 4="very true". The score range is 20-80; Higher scores indicate more anxiety. | PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies). | Posted | Mean | Standard Deviation | score | Before and after 5 weeks of study product intake. |
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| Secondary | Changes in Pre and Post Treatment Perceived Stress Scale (PSS) Scores | Efficacy of the intake of Lpc-37 on the reduction of Perceived Stress Scale (PSS) scores compared to placebo. Measured with the german version of the PSS as a psychological instrument for measuring stress perception. It assesses how unpredictable, uncontrollable and overloaded participants perceived their lives to have been within the last month. The PSS comprises 14 items that are answered on a five-point rating scale ranging from 0 = "never" to 4 = "very often". Individual scores on the PSS can range from 0 to 56 with higher scores indicating higher perceived stress. | PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies). | Posted | Mean | Standard Deviation | score | Before and after 5 weeks of study product intake. |
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| Secondary | Changes in Pre and Post Treatment DASS Depression Scores | Efficacy of the intake of Lpc-37 on the reduction of Depression Anxiety Stress Scale (DASS) depression scores compared to placebo. Measured with the german version of the DASS as a 42-item self report instrument designed to measure negative emotional states of depression, anxiety and stress during the past week. The DASS includes three scales (depression, anxiety and stress) of which each scale includes 14 items that are divided into subscales of 2-5 items of similar content. Items are answered on a four point rating scale ranging from 0 = "not at all" to 3 = "very much". Scores of each scale are calculated by summing the scores for the relevant items. The Depression scale assesses dysphoria, hopelessness, devaluation of life, self-deprecation, lack of interest/involvement, anhedonia, and inertia. The items are 3, 5, 10, 13, 16, 17, 21, 24, 26, 31, 34, 37, 38, 42 and individual scores can range from 0 to 42 with higher scores indicating greater severity of the symptoms. | PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies). | Posted | Mean | Standard Deviation | score | Before and after 5 weeks of study product intake. |
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| Secondary | Changes in Pre and Post Treatment DASS Anxiety Scores | Efficacy of the intake of Lpc-37 on the reduction of Depression Anxiety Stress Scale (DASS) anxiety scores compared to placebo. Measured with the german version of the DASS as a 42-item self report instrument designed to measure negative emotional states of depression, anxiety and stress during the past week. The DASS includes three scales (depression, anxiety and stress) of which each scale includes 14 items that are divided into subscales of 2-5 items of similar content. Items are answered on a four point rating scale ranging from 0 = "not at all" to 3 = "very much". Scores of each scale are calculated by summing the scores for the relevant items. The anxiety scale assesses autonomic arousal, skeletal muscle effects, situational anxiety, and subjective experience of anxious affect. The items are 2, 4, 7, 9, 15, 19, 20, 23, 25, 28, 30, 36, 40, 41 and individual scores can range from 0 to 42 with higher scores indicating greater severity of the symptoms. | PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies). | Posted | Mean | Standard Deviation | score | Before and after 5 weeks of study product intake. |
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| Secondary | Changes in Pre and Post Treatment DASS Stress Scores | Efficacy of the intake of Lpc-37 on the reduction of Depression Anxiety Stress Scale (DASS) stress scores compared to placebo. Measured with the german version of the DASS as a 42-item self report instrument designed to measure negative emotional states of depression, anxiety and stress during the past week. The DASS includes three scales (depression, anxiety and stress) of which each scale includes 14 items that are divided into subscales of 2-5 items of similar content. Items are answered on a four point rating scale ranging from 0 = "not at all" to 3 = "very much". Scores of each scale are calculated by summing the scores for the relevant items. The stress scale (items) is sensitive to levels of chronic non-specific arousal.The stress scale items are 1, 6, 8, 11, 12, 14, 18, 22, 27, 29, 32, 33, 35, 39 and individual scores can range from 0 to 42 with higher scores indicating greater severity of the symptoms. | PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies). | Posted | Mean | Standard Deviation | score | Before and after 5 weeks of study product intake. |
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| Secondary | Changes in Pre and Post Treatment BAI Scores | Efficacy of the intake of Lpc-37 on the reduction of Beck Anxiety Inventory (BAI) scores compared to placebo. Measured with the german version of the Beck Anxiety Inventory as a self-rating scale designed to measure anxiety. It comprises 21 sentences describing feelings that can occur when being anxious. These sentences are rated on a four-point rating scale ranging from 0="not at all" to 3="severely", considering the last 7 days. The score range is 0-63; Higher scores indicate higher anxiety. | PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies). | Posted | Mean | Standard Deviation | score | Before and after 5 weeks of study product intake. |
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| Secondary | Changes in Pre and Post Treatment VAS Stress Perception Scores | Efficacy of the intake of Lpc-37 on the reduction of Visual Analog Scale (VAS) stress perception scores compared to placebo. Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating higher perceived stress. | PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies). | Posted | Mean | Standard Deviation | score | Before and after 5 weeks of study product intake. |
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| Secondary | Changes in Pre and Post Treatment VAS Anxiety Scores | Efficacy of the intake of Lpc-37 on the reduction of VAS anxiety scores compared to placebo. Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater anxiety. | PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies). | Posted | Mean | Standard Deviation | score | Before and after 5 weeks of study product intake. |
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| Secondary | Changes in Pre and Post Treatment VAS Insecurity Scores | Efficacy of the intake of Lpc-37 on the reduction of VAS insecurity scores compared to placebo. Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater insecurity. | PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies). | Posted | Mean | Standard Error | score | Before and after 5 weeks of study product intake. |
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| Secondary | Changes in Pre and Post Treatment VAS Exhaustion Scores | Efficacy of the intake of Lpc-37 on the reduction of VAS exhaustion scores compared to placebo. Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater exhaustion. | PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies). | Posted | Mean | Standard Deviation | score | Before and after 5 weeks of study product intake. |
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| Secondary | Changes in Pre and Post Treatment Systolic BP | Efficacy of the intake of Lpc-37 on the reduction of systolic blood pressure (BP). | PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies). | Posted | Mean | Standard Deviation | mmHg | Before and after 5 weeks of study product intake. |
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| Secondary | Changes in Pre and Post Treatment Diastolic BP | Efficacy of the intake of Lpc-37 on the reduction of diastolic BP. | PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies). | Posted | Mean | Standard Deviation | mmHg | Before and after 5 weeks of study product intake. |
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| Secondary | Change of STAI-State Scores in Response to the TSST | Efficacy of the intake of Lpc-37 on reduction of the increase of STAI-State scores in response to the TSST compared to placebo. Measured with the german version of the State-Trait-Anxiety Inventory, scale anxiety as a temporary emotional state (STAI-X1). Answers are given on a four-point rating scale ranging from 1="not at all" to 4="very true". The score range is 20-80; Higher scores indicate more anxiety. | PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies). | Posted | Mean | Standard Deviation | score | 10 minutes before the TSST and 1 minute after the TSST after 5 weeks of study product intake |
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| Secondary | Change of Systolic BP in Response to the TSST | Efficacy of the intake of Lpc-37 on reduction of the increase of the systolic BP in response to the TSST compared to placebo. | PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies). | Posted | Mean | Standard Deviation | mmHg | 3 minutes before the TSST and 1 minute after the TSST after 5 weeks of study product intake |
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| Secondary | Change of Diastolic Blood Pressure (BP) in Response to the TSST | Efficacy of the intake of Lpc-37 on reduction of the increase of the diastolic BP in response to the TSST compared to placebo. | PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies). | Posted | Mean | Standard Deviation | mmHg | 3 minutes before the TSST and 1 minute after the TSST after 5 weeks of study product intake |
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| Secondary | Change of VAS Stress Perception Scores in Response to the TSST | Efficacy of the intake of Lpc-37 on reduction of the increase of VAS Stress perception scores in response to the TSST compared to placebo. Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating higher perceived stress. | PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies). | Posted | Mean | Standard Deviation | score | 10 minutes before the TSST, during the TSST and 1 minute after the TSST after 5 weeks of study product intake |
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| Secondary | Change of VAS Anxiety Scores in Response to the TSST | Efficacy of the intake of Lpc-37 on reduction of the increase of VAS anxiety scores in response to the TSST compared to placebo. Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater anxiety. | PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies). | Posted | Mean | Standard Deviation | score | 10 minutes before the TSST, during the TSST and 1 minute after the TSST after 5 weeks of study product intake |
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| Secondary | Change of VAS Insecurity Scores in Response to the TSST | Efficacy of the intake of Lpc-37 on reduction of the increase of VAS insecurity scores in response to the TSST compared to placebo. Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater insecurity. | PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies). | Posted | Mean | Standard Deviation | score | 10 minutes before the TSST, during the TSST and 1 minute after the TSST after 5 weeks of study product intake |
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| Secondary | Change of VAS Exhaustion Scores in Response to the TSST | Efficacy of the intake of Lpc-37 on reduction of the increase of VAS exhaustion scores in response to the TSST compared to placebo. Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater exhaustion. | PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies). | Posted | Mean | Standard Deviation | score | 10 minutes before the TSST, during the TSST and 1 minute after the TSST after 5 weeks of study product intake |
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| Secondary | Change of Salivary Cortisol in Response to the TSST | Efficacy of the intake of Lpc-37 on reduction of the increase of salivary cortisol in response to the TSST compared to placebo. | PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies). | Posted | Mean | Standard Deviation | nmol/L | 1 minute before the TSST and 1, 10, 20, 30 and 45 minutes after the TSST after 5 weeks of study product intake |
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| Secondary | Change of sAA in Response to the TSST | Efficacy of the intake of Lpc-37 on reduction of the increase of salivary Alpha-Amylase (sAA) in response to the TSST compared to placebo. | PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies). | Posted | Mean | Standard Deviation | U/ml | 1 minute before the TSST and 1, 10, 20, 30 and 45 minutes after the TSST after 5 weeks of study product intake |
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| Secondary | Change of Sleep Duration Over the Course of the Treatment | Efficacy of the intake of Lpc-37 on the increase of sleep duration over the course of the treatment. Sleep duration was monitored through the wash-out phase (week 1 and 2) and the subsequent treatment phase (weeks 3-7). Efficacy is defined as an increase, or (in case of a general decrease) reduced decrease for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one value for each day and participant. Summary measures for Sleep duration for the averaged ratings per participant and week | PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies). | Posted | Mean | Standard Deviation | min | Daily for 2 weeks before treatment intake and 5 weeks during treatment intake |
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| Secondary | Change of Sleep Related Recovery Scores Over the Course of the Treatment | Efficacy of the intake of Lpc-37 on the increase of sleep related recovery scores over the course of the treatment. Measured with a daily online diary. Sleep related recovery was rated by participants on an 11-point scale (0-10; "not at all" to "very") and monitored throughout the wash-out phase (Week 1 and 2) and the subsequent treatment phase (weeks 3-7). High scores indicate a high recovery. Efficacy is defined as an increase, or (in case of a general decrease) reduced decrease for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one value for each day and participant. Summary measures for sleep related recovery for the averaged ratings per participant and week. | PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies). | Posted | Mean | Standard Deviation | score | Daily for 2 weeks before treatment intake and 5 weeks during treatment intake |
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| Secondary | Change of Reported Sleep Disruptions Over the Course of the Treatment by Week (Proportion Yes/Total) | Efficacy of the intake of Lpc-37 on the decrease of sleep disruptions over the course of the treatment measured with a daily online diary (Proportion (yes/total)). Sleep disruptions were monitored through the wash-out phase and the subsequent treatment phase for each week. In the binary version, the value is either Yes or No for each day and each participant. Efficacy is defined as a decrease, or (in case of a general increase) reduced increase for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one value for each day and participant. The proportion of participants with at least one sleep disruption by treatment group is given, treatment commenced after week 2. Data listed here reflect the proportion of participants who answered "Yes" (e.g. 0,477 * 44 = 20.99 participants answered with "Yes" in week 1 in the Lpc-37 group). | PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies and is listet for each endpoint). | Posted | Number | Proportion of participants (yes/total) | Daily for 2 weeks before treatment intake and 5 weeks during treatment intake |
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| Secondary | Change of Reported Number of Sleep Disruptions Over the Course of the Treatment | Efficacy of the intake of Lpc-37 on the decrease of reported number of sleep disruptions over the course of the treatment measured with a daily online diary (mean of week summary). Sleep disruptions were monitored through the wash-out phase (Week 1 and 2) and the subsequent treatment phase (Weeks 3-7). In the count version, the value can be 0 or a natural number for each day and each participant. Efficacy is defined as a decrease, or (in case of a general increase) reduced increase for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one value for each day and participant. Values reflect summary measures for sleep disruptions (count) for the summed counts per participant and week. | PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies). | Posted | Mean | Standard Deviation | sleep disruptions per participant & week | Daily for 2 weeks before treatment intake and 5 weeks during treatment intake |
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| Secondary | Change of Perceived Health Status Scores Over the Course of the Treatment | Efficacy of the intake of Lpc-37 on the increase of perceived health status scores over the course of the treatment. Measured with a daily online diary. Health status was rated by participants on an 11-point scale (0-10; "not at all" to "very") and monitored through the wash-out phase (week 1 and 2) and the subsequent treatment phase (weeks 3-7). Higher scores indicate a high perceived health.Efficacy is defined as an increase, or (in case of a general decrease) reduced decrease for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one value for each day and participant. Values reflect summary measures for perceived health status on a scale from 0 to 10 for the averaged ratings per participant and week. | PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies). | Posted | Mean | Standard Deviation | score | Daily for 2 weeks before treatment intake and 5 weeks during treatment intake |
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| Secondary | Change of Mood Scale Scores Over the Course of the Treatment | Efficacy of the intake of Lpc-37 on the increase of mood scale scores over the course of the treatment Measured with a daily online diary. Mood was rated by participants on an 11-point scale (0-10; "very bad" to "very well") and monitored through the washout phase (week 1 and 2) and the subsequent treatment phase (weeks 3-7). Higher scores indicate a better mood. Efficacy is defined as an increase, or (in case of a general decrease) reduced decrease for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one average value for each week and participant. Values reflect summary measures for mood ratings on a scale from 0 to 10 for the averaged ratings per participant and week. | PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies). | Posted | Mean | Standard Deviation | score | Daily for 2 weeks before treatment intake and 5 weeks during treatment intake |
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| Secondary | Change of Perceived Productivity Scores Over the Course of the Treatment | Efficacy of the intake of Lpc-37 on the increase of perceived productivity scores over the course of the treatment Measured with a daily online diary. Productivity was rated by participants on an 11-point scale (0-10; "not at all" to "very") and monitored through the wash-out phase (week 1 and 2) and the subsequent treatment phase (weeks 3-7). Higher scores indicate a higher perceived productivity. Efficacy is defined as an increase, or (in case of a general decrease) reduced decrease for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group.Time is coded as a continuous variable with one value for each day and participant. The values reflect summary measures for perceived productivity on a scale from 0 to 10 for the averaged ratings per participant and week. | PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies). | Posted | Mean | Standard Deviation | score | Daily for 2 weeks before treatment intake and 5 weeks during treatment intake |
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| Secondary | The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of CAR AUCg Measures | Efficacy of the intake of Lpc-37 on the reduction of the difference of Cortisol Awakening Response (CAR) area under the curve with respect to the ground (AUCg) values to the respective mean before and after 5 weeks of treatment. The CAR is summarized in the variables AUCg, AUCi, mean increase and peak value. These cortisol indices are frequently used to describe hypothalamic-pituitary-adrenal axis activity and represent information either of the total cortisol production or of the change in cortisol levels. AUCg is the total area under the curve of all measurements (i.e., the intensity or magnitude of the response). Efficacy for the CAR variables AUCg is defined in terms of a normalization: Number of participants with normal values (between first and third quantile of reference measures) and numbers of participants with low or high values are compared before treatment and after treatment. More participants in the normal range after treatment is defined as efficacy. | PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies). | Posted | Number | number of participants | Baseline (average of 2 days before first product intake) and end of study (average of 2 days before last product intake) |
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| Secondary | The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of Cortisol Awakening Response (CAR) AUCi Measures | Efficacy of the intake of Lpc-37 on the reduction of the difference of CAR area under the curve with respect to the increase (AUCi) values to the respective mean before and after the treatment. The CAR is summarized in the variables AUCg, AUCi, mean increase and peak value. These cortisol indices are frequently used to describe hypothalamic-pituitary-adrenal axis activity and represent information either of the total cortisol production or of the change in cortisol levels. AUCi is calculated with reference to the baseline measurement and it ignores the distance from zero for all measurements and emphasizes the changes over time. Efficacy for the CAR variables AUCi is defined in terms of a normalization: Number of participants with normal values (between first and third quantile of reference measures) and numbers of participants with low or high values are compared before treatment and after treatment. More participants in the normal range after treatment is defined as efficacy. | PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies). | Posted | Number | number of participants | Baseline (average of 2 days before first product intake) and end of study (average of 2 days before last product intake) |
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| Secondary | The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of Cortisol at Awakening Measures | Efficacy of the intake of Lpc-37 on the reduction of the difference of Cortisol at Awakening values to the respective mean before and after 5 weeks of treatment Efficacy for the CAR variable cortisol at awakening is defined in terms of a normalization: Number of participants with normal values (between first and third quantile of reference measures) and numbers of participants with low or high values are compared before treatment and after treatment. More participants in the normal range after treatment is defined as efficacy. | PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies). | Posted | Number | number of participants | Baseline (average of 2 days before first product intake) and end of study (average of 2 days before last product intake) |
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| Secondary | The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of CAR 8pm Measures | Efficacy of the intake of Lpc-37 on the reduction of the difference of cortisol at 8 pm values to the respective mean before and after 5 weeks of treatment Efficacy for the CAR variable cortisol at 8 pm is defined in terms of a normalization: Number of participants with normal values (between first and third quantile of reference measures) and numbers of participants with low or high values are compared before treatment and after treatment. More participants in the normal range after treatment is defined as efficacy. | PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies). | Posted | Number | number of participants | Baseline (average of 2 days before first product intake) and end of study (average of 2 days before last product intake |
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| EG001 | Placebo | Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups. | 0 | 59 | 0 | 59 | 26 | 59 |
| sore throat | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| headache | Nervous system disorders | Systematic Assessment |
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| stomach ache | Gastrointestinal disorders | Systematic Assessment |
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| Head cold | Infections and infestations | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Vertigo | Cardiac disorders | Systematic Assessment |
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| Discomfort/Complaints related to the menstrual cycle | General disorders | Systematic Assessment |
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