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| ID | Type | Description | Link |
|---|---|---|---|
| 2025-A01248-41 | Other Identifier | ID-RCB |
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Obesity is a prevalent chronic disease affecting 17% of the French population. Treatment involves multiple factors, with pharmacotherapy playing an increasingly important role. GLP-1 receptor agonists (GLP1 RAs) are considered revolutionary in obesity treatment, with three approved molecules available in France: liraglutide, semaglutide, and tirzepatide. These treatments, combined with a healthy lifestyle, induce significant weight loss: 9% with liraglutide, 15% with semaglutide, and 20% with tirzepatide.
The most common adverse events (AEs) associated with GLP-1 RAs are gastrointestinal (GI) disorders, including nausea, vomiting, diarrhea, and abdominal pain. These AEs are dose-dependent and often decline over time. In phase 3 trials, semaglutide 2.4 mg showed higher rates of GI AEs compared to placebo, but most were mild to moderate and transient. GI AEs led to dose reduction or temporary treatment interruption in 12.5% of participants, with few permanent discontinuations.
Probiotics, are live microorganisms that benefit the host by improving gut microflora. Probiotics has been clinically proven to benefit gastrointestinal health. Probiotics may reduces symptoms of irritable bowel syndrome (IBS), improves gut barrier function, reduces inflammation, and decreases the incidence of C. difficile infection (CDI) in patients taking antibiotics.
Probiotics is therefore theorized to potentially reduce GI side effects associated with GLP-1 RA treatment for obesity.
Hypothesis Probiotics will prevent and limit the digestive disorders induced by GLP-1 R agonists, particularly during the dose escalation period. This would allow better digestive tolerance of the treatments, limiting the number of definitive treatment interruptions, facilitating compliance and dose escalation with a larger number of subjects at full dose and therefore with better systemic exposure to the compounds, a key factor in their effects on weight loss.
Obesity is a prevalent chronic disease affecting 17% of the French population. Treatment involves multiple factors, with pharmacotherapy playing an increasingly important role. GLP-1 receptor agonists (GLP1 RAs) are considered revolutionary in obesity treatment, with three approved molecules available in France: liraglutide, semaglutide, and tirzepatide. These treatments, combined with a healthy lifestyle, induce significant weight loss: 9% with liraglutide, 15% with semaglutide, and 20% with tirzepatide.
The most common adverse events (AEs) associated with GLP-1 RAs are gastrointestinal (GI) disorders, including nausea, vomiting, diarrhea, and abdominal pain. These AEs are dose-dependent and often decline over time. In phase 3 trials, semaglutide 2.4 mg showed higher rates of GI AEs compared to placebo, but most were mild to moderate and transient. GI AEs led to dose reduction or temporary treatment interruption in 12.5% of participants, with few permanent discontinuations.
Probiotics, are live microorganisms that benefit the host by improving gut microflora. Probiotics has been clinically proven to benefit gastrointestinal health. Probiotics may reduces symptoms of irritable bowel syndrome (IBS), improves gut barrier function, reduces inflammation, and decreases the incidence of C. difficile infection (CDI) in patients taking antibiotics.
Probiotics is therefore theorized to potentially reduce GI side effects associated with GLP-1 RA treatment for obesity.
Hypothesis Probiotics will prevent and limit the digestive disorders induced by GLP-1 R agonists, particularly during the dose escalation period. This would allow better digestive tolerance of the treatments, limiting the number of definitive treatment interruptions, facilitating compliance and dose escalation with a larger number of subjects at full dose and therefore with better systemic exposure to the compounds, a key factor in their effects on weight loss.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Probiotics | Experimental | Obese subjects who are going to start a GLP-1 R-agonist (semaglutide or tirzepatide) as part of their weight management in routine clinical practice will received during 26 weeks 1 capsule a day every morning of probiotics that will begin 2 weeks before the initiation of semaglutide or tirzepatide treatment. |
|
| Placebo | Placebo Comparator | Obese subjects who are going to start a GLP-1 R-agonist (semaglutide or tirzepatide) as part of their weight management in routine clinical practice will received during 26 weeks 1 capsule a day every morning of PLACEBO that will begin 2 weeks before the initiation of semaglutide or tirzepatide treatment. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Probiotics (Natural product) | Dietary Supplement | Participants will be instructed to daily take, during 26 weeks (that will begin 2 weeks before the initiation of semaglutide or tirzepatide treatment) one capsule of a probiotic with water at room temperature with the first meal. Dosage levels: 1 capsule Digestive Quality of life during the study will be assessed. |
| Measure | Description | Time Frame |
|---|---|---|
| Assessment of the Limitation of the impairment in digestive quality of life during the dose escalation of GLP1-RA (semaglutide or tirzepatide) | Assessment using partial GIQLI Score (5 items: 1,27,31,32,33 of the total GIQLI) in each GLP-1 RA group measured 4 weeks following the previous dose escalation, with the GLP1-RA dose standardized on a 0-1 scale. Item 1 for abdominal pain, Item 27 for dyspepsia, Item 31 for diarrhea, item 32 for constipation and Item 33 for nausea. For each item, 5 responses will be proposed to the patients and for each answer, a score ranging from 0 to 4 will be assigned The highest score is 20 and defines a more favorable health state | Every 5 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Digestive quality of life | Comparison between the probiotic group and placebo group in the whole population and in the subpopulation of subjects having reached the planned GLP-1 RA treatment dose at 24 weeks, according to the dose escalation design: Evolution of the partial GIQLI Scores (Questions 1,27,31,32,33). Item 1 for abdominal pain, Item 27 for dyspepsia, Item 31 for diarrhea, item 32 for constipation and Item 33 for nausea. For each item, 5 responses and for each answer, a score ranging from 0 to 4. The highest score is 20 and defines a more favorable health state |
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Inclusion Criteria:
Exclusion Criteria:
Criteria relating to the study population:
Product criteria:
Patient with known allergy to the product of the study
Prohibited treatments :
Current associated treatments or used in the last 30 days: GLP-1 RA, Anti-obesity drugs (AOD), Corticosteroids, Atypical neuroleptics, Antibiotics, Probiotics, Prebiotics
Regulatory criteria :
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Emmanuel DISSE, PUPH | Contact | +33478861484 | Emmanuel.disse@chu-lyon.fr | |
| Dominique DELAUNAY, PhD | Contact | +33472110064 | Dominique.delaunay@chu-lyon.Fr |
| Name | Affiliation | Role |
|---|---|---|
| Emmanuel DISSE, PUPH | Hospices Civils de Lyon | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hôpital Lyon Sud | Pierre-Bénite | 69495 | France |
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| ID | Term |
|---|---|
| D009765 | Obesity |
| D050177 | Overweight |
| D004066 | Digestive System Diseases |
| ID | Term |
|---|---|
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
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| ID | Term |
|---|---|
| D019936 | Probiotics |
| D001688 | Biological Products |
| ID | Term |
|---|---|
| D019587 | Dietary Supplements |
| D005502 | Food |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
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Prospective, double blind, randomized, monocentric, 2 parallel groups (1:1) study evaluating superiority probiotics over placebo in limiting the impairment in digestive quality of life over 24-week in patients with obesity initiating GLP-1 RA (semaglutide or tirzepatide) for weight control.
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Double-blind study : patients and investigators will not be informed of the approach (probiotics or placebo ) which will be used.
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| Placebo | Other | Participants will be instructed to daily take, during 26 weeks (that will begin 2 weeks before the initiation of semaglutide or tirzepatide treatment) one capsule of PLACEBO with water at room temperature with the first meal. Digestive Quality of life during the study will be assessed. |
|
| From baseline to 4, 8, 12, 16, 20 and 24 weeks of treatment |
| Nausea | Comparison of nausea between the probiotic group and placebo group in the whole population and in the subpopulation of subjects having reached the planned GLP-1 RA treatment dose at 24 weeks, according to the dose escalation design: Evolution of partial GIQLI score (question 33) of nausea score ranging from 0 to 4. 4 defines the more favourable score | From baseline to 4, 8, 12, 16, 20 and 24 weeks of treatment |
| Dyspepsia | Comparison of dyspepsia between the probiotic group and placebo group in the whole population and in the subpopulation of subjects having reached the planned GLP-1 RA treatment dose at 24 weeks, according to the dose escalation design: Evolution of partial GIQLI score (question 27) of dyspepsia score ranging from 0 to 4. 4 defines the more favourable score | From baseline to 4, 8, 12, 16, 20 and 24 weeks of treatment |
| Diarrhea | Comparison of diarrhea between the probiotics group and placebo group in the whole population and in the subpopulation of subjects having reached the planned GLP-1 RA treatment dose at 24 weeks, according to the dose escalation design: Evolution of partial GIQLI score (question 31) of diarrhea score ranging from 0 to 4. 4 defines the more favourable score | From baseline to 4, 8, 12, 16, 20 and 24 weeks of treatment |
| Constipation | Comparison of constipation between the probiotic group and placebo group in the whole population and in the subpopulation of subjects having reached the planned GLP-1 RA treatment dose at 24 weeks, according to the dose escalation design: Evolution of partial GIQLI score (question 32) of constipation score ranging from 0 to 4. 4 defines the more favourable score | From baseline to 4, 8, 12, 16, 20 and 24 weeks of treatment |
| Abdominal pain | Comparison of abdominal pain between the probiotic group and placebo group in the whole population and in the subpopulation of subjects having reached the planned GLP-1 RA treatment dose at 24 weeks, according to the dose escalation design: Evolution of partial GIQLI score (question 1) of abdominal pain score ranging from 0 to 4. 4 defines the more favourable score | From baseline to 4, 8, 12, 16, 20 and 24 weeks of treatment |
| GLP-1 receptor agonist dosage | Average GLP-1 RA dose | 4, 8, 12, 16, 20 and 24 weeks of intervention |
| GLP1-RA dose escalation | Proportion of patients having reached the planned GLP-1 RA treatment dose according to the dose escalation protocol at 4, 8, 12, 16, 20 and 24 weeks | 4, 8, 12, 16, 20 and 24 weeks of intervention |
| GLP1-RA dose discontinuation/maintenance | Proportion of patients who had to reduce or to interrupt definitively their GLP-1 RA treatment dose at 4, 8, 12, 16, 20 and 24 weeks | 4, 8, 12, 16, 20 and 24 weeks of intervention |
| Weight loss | Percent of weight change from baseline | 4, 8, 12, 16, 20 and 24 weeks of intervention |
| Weight loss | absolute change in body weight from baseline | 4, 8, 12, 16, 20 and 24 weeks of intervention |
| Weight loss | Rate of patients achieving a body weight reduction of ≥5%, ≥10%, ≥15% | 4, 8, 12, 16, 20 and 24 weeks of intervention |
| Quality of life assessed with GIQLI questionnaire | This questionnaire consists of 36 items exploring 5 dimensions or subscales: symptoms, physical condition, emotions, social integration and the effect of any medical treatment. For each item, 5 responses will be proposed to the patients and for each answer, a score ranging from 0 to 4 (highest score = 144) will be assigned. A high score defines a more favorable health state. | baseline, 12 and 24 weeks of treatment |
| Quality of life assessed with SF36 questionnaire | This questionnaire taps eight health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/tiredness, and general health perceptions. It also includes a single item that provides an indication of a perceived change in health | baseline, 12 and 24 weeks of treatment |
| Fat mass | Measurement of fat mass will explore the body composition. Results will be expressed in kg and % | Baseline, before implementation of GLP1-RA, 12 and 24 weeks of treatment |
| Lean mass | Measurement of lean mass will explore the body composition. Results will be expressed in kg and % | Baseline, before implementation of GLP1-RA, 12 and 24 weeks of treatment |
| Skeletal muscle mass | Measurement of skeletal muscle mass will explore the body composition. Results will be expressed in kg and % | Baseline, before implementation of GLP1-RA, 12 and 24 weeks of treatment |
| Adverse Events | The safety will be assessed by the Number of adverse events, linked or not to the study product | After 4, 8, 12, 16, 20 and 24 weeks of treatment. |
| Severe Adverse Events | The safety will be assessed by the number of severe adverse events, linked or not to the study product | After 4, 8, 12, 16, 20 and 24 weeks of treatment. |
| Intestinal microbiota | Fecal microbiota composition | Baseline and 24 weeks of treatment |
| D012816 |
| Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D019602 |
| Food and Beverages |
| D045424 | Complex Mixtures |