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Covid-19
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This randomized double-blind placebo-controlled crossover study seeks to evaluate the antidepressant effect of L-leucine, an essential amino acid, in patients with Major Depressive Disorder (MDD).
This is a pilot phase II clinical trial of L-leucine to test its efficacy in reducing depressive symptoms in MDD patients, especially those who exhibit increased inflammation. The determination of increased inflammation will be done post-hoc. During the screening visit, all study participants will provide demographic information and complete self-report assessments and clinician evaluations and examinations. Blood and urine tests will also be performed. All participants who meet eligibility criteria and are willing to proceed with the study will enter this 6-week study after being randomized to two-week course of either L-leucine or placebo. In this cross-over study, participants will be crossed over to the second treatment after 2 weeks of washout. The study period will last 42 days (6 weeks) from the baseline visit. Both L-leucine and placebo will be provided as an effervescent mixture powder. Investigators hypothesize that MDD subjects will have greater reduction in depression severity on leucine as compared to placebo.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| L-leucine | Experimental | 4 gm L-leucine by mouth twice daily for two weeks |
|
| Maltodextrin | Placebo Comparator | 4 gm maltodextrin by mouth twice daily for two weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| L-Leucine | Drug | L-leucine is an essential amino acid which will be provided as an effervescent powder mixture to participants. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in QIDS-SR From Baseline at 14 Days | The Quick Inventory of Depressive Symptomatology, self-report (QIDS-SR), self-report is a 16-item measure of depression severity that includes the 9 criterion symptoms for MDD. Items are scored on a 4-point Likert scale, ranging from 0 to 3 (total score range, 0-27). Totals scores of ≤ 5 indicate no depression; 6-10 indicates mild depression; 11-15 indicates moderate depression; 16-20 indicates severe depression; and ≥ 21 indicates very severe depression. For purposes of this report, severe and very severe categories were combined as "severe to very severe" depression (≥ 16). The QIDS-A self-report has demonstrated acceptable psychometric properties. | Baseline to 14 days |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of MDD Patients With 50% or Greater Reduction in Depression Severity After 14 Days of LEU and PBO Treatments. | Response criteria defined based on QIDS-SR score at baseline and 14 days after treatment initiation. The Quick Inventory of Depressive Symptomatology, self-report (QIDS-SR), self-report is a 16-item measure of depression severity that includes the 9 criterion symptoms for MDD. Items are scored on a 4-point Likert scale, ranging from 0 to 3 (total score range, 0-27). Totals scores of ≤ 5 indicate no depression; 6-10 indicates mild depression; 11-15 indicates moderate depression; 16-20 indicates severe depression; and ≥ 21 indicates very severe depression. For purposes of this report, severe and very severe categories were combined as "severe to very severe" depression (≥ 16). The QIDS-A self-report has demonstrated acceptable psychometric properties. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Madhukar H Trivedi, M.D. | University of Texas Southwestern Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Texas Southwestern Medical Center | Dallas | Texas | 75390 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18073775 | Background | Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci. 2008 Jan;9(1):46-56. doi: 10.1038/nrn2297. | |
| 28187400 | Background | Jha MK, Minhajuddin A, Gadad BS, Greer T, Grannemann B, Soyombo A, Mayes TL, Rush AJ, Trivedi MH. Can C-reactive protein inform antidepressant medication selection in depressed outpatients? Findings from the CO-MED trial. Psychoneuroendocrinology. 2017 Apr;78:105-113. doi: 10.1016/j.psyneuen.2017.01.023. Epub 2017 Jan 24. |
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16 participants were consented, of which 5 were determined as eligible after screening. Of those 5, 1 reported exclusionary criteria at the baseline visit and 4 were randomized.
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| ID | Title | Description |
|---|---|---|
| FG000 | L-leucine, Then Placebo | Participants with 4 gm L-leucine by mouth twice daily for two weeks, then washout for two weeks, then 4 gm maltodextrin by mouth twice daily for two weeks. |
| FG001 | Placebo, Then L-leucine | Participants start with 4 gm maltodextrin by mouth twice daily for two weeks, then washout for two weeks, then 4 gm L-leucine by mouth twice daily for two weeks. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention (14 Days) |
| |||||||||||||
| Washout (14 Days) |
| |||||||||||||
| Second Intervention (14 Days) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | A/B (L-leucine/Maltodextrin) | Starts with 4 gm L-leucine by mouth twice daily for two weeks, then washout for two weeks, then 4 gm maltodextrin by mouth twice daily for two weeks. |
| BG001 | B/A (Maltodextrin/L-leucine) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 in QIDS-SR From Baseline at 14 Days | The Quick Inventory of Depressive Symptomatology, self-report (QIDS-SR), self-report is a 16-item measure of depression severity that includes the 9 criterion symptoms for MDD. Items are scored on a 4-point Likert scale, ranging from 0 to 3 (total score range, 0-27). Totals scores of ≤ 5 indicate no depression; 6-10 indicates mild depression; 11-15 indicates moderate depression; 16-20 indicates severe depression; and ≥ 21 indicates very severe depression. For purposes of this report, severe and very severe categories were combined as "severe to very severe" depression (≥ 16). The QIDS-A self-report has demonstrated acceptable psychometric properties. | Posted | Mean | Standard Deviation | score on a scale | Baseline to 14 days |
|
Adverse Event data was collected for each participant from their Baseline Visit (Day 0) to Day 42, for a total of 43 days.
Adverse events were assessed at the end of each visit.
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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 | L-leucine | AE was reported with a start date within the two week period subject was taking 4 gm L-leucine by mouth twice daily |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutrophil count low | Investigations | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Maria Monastirsky | University of Texas Southwestern | 214-648-0174 | Maria.Monastirsky@utsouthwestern.edu |
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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 | Aug 16, 2016 | Sep 28, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D003865 | Depressive Disorder, Major |
| D007249 | Inflammation |
| D003863 | Depression |
| D061218 | Depressive Disorder, Treatment-Resistant |
| ID | Term |
|---|---|
| D003866 | Depressive Disorder |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
| D010335 | Pathologic Processes |
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| ID | Term |
|---|---|
| D007930 | Leucine |
| C008315 | maltodextrin |
| ID | Term |
|---|---|
| D000597 | Amino Acids, Branched-Chain |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000601 | Amino Acids, Essential |
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| Maltodextrin | Other | Maltodextrin is a nonsweet carbohydrate which will be provided as an effervescent powder mixture similar in taste and appearance to the L-leucine containing effervescent powder mixture |
|
|
| Baseline to 14 days |
| Percentage of MDD Patients With QIDS-SR Score Less Than or Equal to 5 at 14 Days of LEU and PBO Treatments. | Remission operationalized as QIDS-SR <=5. The Quick Inventory of Depressive Symptomatology, self-report (QIDS-SR), self-report is a 16-item measure of depression severity that includes the 9 criterion symptoms for MDD. Items are scored on a 4-point Likert scale, ranging from 0 to 3 (total score range, 0-27). Totals scores of ≤ 5 indicate no depression; 6-10 indicates mild depression; 11-15 indicates moderate depression; 16-20 indicates severe depression; and ≥ 21 indicates very severe depression. For purposes of this report, severe and very severe categories were combined as "severe to very severe" depression (≥ 16). The QIDS-A self-report has demonstrated acceptable psychometric properties. | 14 days |
| Rates of Adverse Effects After 3 Days, 7 Days and 14 Days of LEU and PBO Treatments. | Adverse effect burden will be measured with Frequency Intensity and Burden of Side-effect rating scale (FIBSER). The Frequency, Intensity, Burden of Side Effects Rating (FIBSER) scale was designed by Dr. Stephen Wisniewski for use in the U.S. STAR*D effectiveness study. It is a 3-item scale to assess side effects from antidepressant treatment. To use the FIBSER in measurement-based care, clinicians should consider item 3 (Burden). If the score is 0 to 2 (None to Mild interference with activities), no change in medication is needed. If the score is 3-4 (Moderate to Marked interference with activites), the side effects need to be addressed (i.e., change in dose, side effect antidote, etc). If the score is 5-6 (Severe interference with activities or Unable to Function), the dose needs to be decreased or the medication needs to be switched. | Baseline to 3 days, 7 days, and 14 days |
| Change in Fatigue Symptoms From Baseline After 3, 7, and 14 Days of LEU and PBO Treatments Measured With Multidimensional Fatigue Inventory. | Fatigue will be measured with Multidimensional fatigue inventory The Multidimensional Fatigue Inventory (MFI) is a 20-item self-report instrument designed to measure fatigue. It contains five scales: general fatigue (items 1, 5, 12, 16), mental fatigue (items 7, 11, 13, 19), physical fatigue (items 2, 8, 14, 20), reduced motivation (items 4, 9, 15, 18) and reduced activity (items 3, 6, 10, 17). Items are scored on a 5-point scale on which the participant expressed the degree to which the statement applied to him or her (from agreement "yes, that is true" to disagreement "no, that is not true") in the previous days. Item scores are summed to create a sum score for each scale, ranging between 4 (best condition) and 20 (worst condition). Higher scores indicate more fatigue. | Baseline to 3 days, 7 days, and 14 days |
| Change in Psychosocial Function From Baseline After 3, 7, and 14 Days of LEU and PBO Treatments Measured Using Work and Social Adjustment Scale. | Psychosocial function will be measured using Work and Social Adjustment Scale The Work and Social Adjustment Scale ("WSAS") is a 5-item measure for impairment in functioning. Items are scored on an 8-point scale on how much participants' problems impaired their ability to carry out the activity (from "Not at all" to "Very severely"). Item scores are summed to create a sum score. The maximum score of the WSAS is 40, lower scores are better. A WSAS score above 20 appears to suggest moderately severe or worse psychopathology. Scores between 10 and 20 are associated with significant functional impairment but less severe clinical symptomatology. Scores below 10 appear to be associated with subclinical populations. | Baseline to 3 days, 7 days, and 14 days |
| Change in Anhedonia From Baseline After 3, 7, and 14 Days of LEU and PBO Treatments Measured Using Snaith-Hamilton Pleasure Scale (SHAPS) | Anhedonia will be measured using Snaith-Hamilton Pleasure Scale (SHAPS). The Snaith-Hamilton Pleasure Scale (SHAPS) is a 14-item scale that measures anhedonia, the inability to experience pleasure. The items cover the domains of: social interaction, food and drink, sensory experience, and interest/pastimes. A score of 2 or less constitutes a "normal" score, while an "abnormal" score is defined as 3 or more. Each item has four possible responses: strongly disagree, disagree, agree, or strongly agree. Either of the "disagree" responses score one point, and either of the "agree" responses score 0 points. Thus, the final score ranges from 0 to 14. | Baseline to 3 days, 7 days, and 14 days |
| 18678792 | Background | Rush AJ, Wisniewski SR, Warden D, Luther JF, Davis LL, Fava M, Nierenberg AA, Trivedi MH. Selecting among second-step antidepressant medication monotherapies: predictive value of clinical, demographic, or first-step treatment features. Arch Gen Psychiatry. 2008 Aug;65(8):870-80. doi: 10.1001/archpsyc.65.8.870. |
| 16554525 | Background | Rush AJ, Trivedi MH, Wisniewski SR, Stewart JW, Nierenberg AA, Thase ME, Ritz L, Biggs MM, Warden D, Luther JF, Shores-Wilson K, Niederehe G, Fava M; STAR*D Study Team. Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. N Engl J Med. 2006 Mar 23;354(12):1231-42. doi: 10.1056/NEJMoa052963. |
| 16554526 | Background | Trivedi MH, Fava M, Wisniewski SR, Thase ME, Quitkin F, Warden D, Ritz L, Nierenberg AA, Lebowitz BD, Biggs MM, Luther JF, Shores-Wilson K, Rush AJ; STAR*D Study Team. Medication augmentation after the failure of SSRIs for depression. N Engl J Med. 2006 Mar 23;354(12):1243-52. doi: 10.1056/NEJMoa052964. |
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| NOT COMPLETED |
|
Starts with 4 gm maltodextrin by mouth twice daily for two weeks, then washout for two weeks, then 4 gm L-leucine by mouth twice daily for two weeks.
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG001 |
| Maltodextrin |
4 gm maltodextrin by mouth twice daily for two weeks |
|
|
|
| Secondary | Percentage of MDD Patients With 50% or Greater Reduction in Depression Severity After 14 Days of LEU and PBO Treatments. | Response criteria defined based on QIDS-SR score at baseline and 14 days after treatment initiation. The Quick Inventory of Depressive Symptomatology, self-report (QIDS-SR), self-report is a 16-item measure of depression severity that includes the 9 criterion symptoms for MDD. Items are scored on a 4-point Likert scale, ranging from 0 to 3 (total score range, 0-27). Totals scores of ≤ 5 indicate no depression; 6-10 indicates mild depression; 11-15 indicates moderate depression; 16-20 indicates severe depression; and ≥ 21 indicates very severe depression. For purposes of this report, severe and very severe categories were combined as "severe to very severe" depression (≥ 16). The QIDS-A self-report has demonstrated acceptable psychometric properties. | Posted | Number | percentage of patients | Baseline to 14 days |
|
|
|
|
| Secondary | Percentage of MDD Patients With QIDS-SR Score Less Than or Equal to 5 at 14 Days of LEU and PBO Treatments. | Remission operationalized as QIDS-SR <=5. The Quick Inventory of Depressive Symptomatology, self-report (QIDS-SR), self-report is a 16-item measure of depression severity that includes the 9 criterion symptoms for MDD. Items are scored on a 4-point Likert scale, ranging from 0 to 3 (total score range, 0-27). Totals scores of ≤ 5 indicate no depression; 6-10 indicates mild depression; 11-15 indicates moderate depression; 16-20 indicates severe depression; and ≥ 21 indicates very severe depression. For purposes of this report, severe and very severe categories were combined as "severe to very severe" depression (≥ 16). The QIDS-A self-report has demonstrated acceptable psychometric properties. | Posted | Number | percentage of patients | 14 days |
|
|
|
|
| Secondary | Rates of Adverse Effects After 3 Days, 7 Days and 14 Days of LEU and PBO Treatments. | Adverse effect burden will be measured with Frequency Intensity and Burden of Side-effect rating scale (FIBSER). The Frequency, Intensity, Burden of Side Effects Rating (FIBSER) scale was designed by Dr. Stephen Wisniewski for use in the U.S. STAR*D effectiveness study. It is a 3-item scale to assess side effects from antidepressant treatment. To use the FIBSER in measurement-based care, clinicians should consider item 3 (Burden). If the score is 0 to 2 (None to Mild interference with activities), no change in medication is needed. If the score is 3-4 (Moderate to Marked interference with activites), the side effects need to be addressed (i.e., change in dose, side effect antidote, etc). If the score is 5-6 (Severe interference with activities or Unable to Function), the dose needs to be decreased or the medication needs to be switched. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline to 3 days, 7 days, and 14 days |
|
|
|
|
| Secondary | Change in Fatigue Symptoms From Baseline After 3, 7, and 14 Days of LEU and PBO Treatments Measured With Multidimensional Fatigue Inventory. | Fatigue will be measured with Multidimensional fatigue inventory The Multidimensional Fatigue Inventory (MFI) is a 20-item self-report instrument designed to measure fatigue. It contains five scales: general fatigue (items 1, 5, 12, 16), mental fatigue (items 7, 11, 13, 19), physical fatigue (items 2, 8, 14, 20), reduced motivation (items 4, 9, 15, 18) and reduced activity (items 3, 6, 10, 17). Items are scored on a 5-point scale on which the participant expressed the degree to which the statement applied to him or her (from agreement "yes, that is true" to disagreement "no, that is not true") in the previous days. Item scores are summed to create a sum score for each scale, ranging between 4 (best condition) and 20 (worst condition). Higher scores indicate more fatigue. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline to 3 days, 7 days, and 14 days |
|
|
|
|
| Secondary | Change in Psychosocial Function From Baseline After 3, 7, and 14 Days of LEU and PBO Treatments Measured Using Work and Social Adjustment Scale. | Psychosocial function will be measured using Work and Social Adjustment Scale The Work and Social Adjustment Scale ("WSAS") is a 5-item measure for impairment in functioning. Items are scored on an 8-point scale on how much participants' problems impaired their ability to carry out the activity (from "Not at all" to "Very severely"). Item scores are summed to create a sum score. The maximum score of the WSAS is 40, lower scores are better. A WSAS score above 20 appears to suggest moderately severe or worse psychopathology. Scores between 10 and 20 are associated with significant functional impairment but less severe clinical symptomatology. Scores below 10 appear to be associated with subclinical populations. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline to 3 days, 7 days, and 14 days |
|
|
|
|
| Secondary | Change in Anhedonia From Baseline After 3, 7, and 14 Days of LEU and PBO Treatments Measured Using Snaith-Hamilton Pleasure Scale (SHAPS) | Anhedonia will be measured using Snaith-Hamilton Pleasure Scale (SHAPS). The Snaith-Hamilton Pleasure Scale (SHAPS) is a 14-item scale that measures anhedonia, the inability to experience pleasure. The items cover the domains of: social interaction, food and drink, sensory experience, and interest/pastimes. A score of 2 or less constitutes a "normal" score, while an "abnormal" score is defined as 3 or more. Each item has four possible responses: strongly disagree, disagree, agree, or strongly agree. Either of the "disagree" responses score one point, and either of the "agree" responses score 0 points. Thus, the final score ranges from 0 to 14. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline to 3 days, 7 days, and 14 days |
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|
|
| 0 |
| 4 |
| 0 |
| 4 |
| 1 |
| 4 |
| EG001 | Washout Following L-Leucine | AE was reported with a start date following (within two weeks) the two week period subject was taking 4 gm L-leucine by mouth twice daily | 0 | 4 | 0 | 4 | 1 | 4 |
| EG002 | Maltodextrin | AE was reported with a start date within the two week period subject was taking 4 gm Maltodextrin by mouth twice daily | 0 | 4 | 0 | 4 | 2 | 4 |
| EG003 | Washout Following Maltodextrin | AE was reported with a start date following (within two weeks) the two week period subject was taking 4 gm Maltodextrin by mouth twice daily | 0 | 4 | 0 | 4 | 2 | 4 |
| White blood cell count low | Investigations | Systematic Assessment |
|
| Pruritis | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Skin Laceration | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Viral upper respiratory tract infection | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| AST Increased | Investigations | Systematic Assessment |
|
| Red blood cell count low | Investigations | Systematic Assessment |
|
| Hemoglobin low | Investigations | Systematic Assessment |
|
| Hematocrit low | Investigations | Systematic Assessment |
|
| Mean cell hemoglobin concentration increased | Investigations | Systematic Assessment |
|
| Platelet count low | Investigations | Systematic Assessment |
|
| Monocyte count low | Investigations | Systematic Assessment |
|
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| D013568 |
| Pathological Conditions, Signs and Symptoms |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
| Adverse effect burden function 14 days Change |
|
| 0.9932 |
P-value for Adverse effect burden 7 days Change. Model: Change from baseline=Baseline, Visit, Treatment, Treatment*Visit |
| Superiority |
| MMRM | 0.2242 | P-value for Adverse effect burden 14 days Change. Model: Change from baseline=Baseline, Visit, Treatment, Treatment*Visit | Superiority |
| General fatigue 14 days Change |
|
| Mental fatigue 3 days Change |
|
| Mental fatigue 7 days Change |
|
| Mental fatigue 14 days Change |
|
| Physical fatigue 3 days Change |
|
| Physical fatigue 7 days Change |
|
| Physical fatigue 14 days Change |
|
| Reduced motivation 3 days Change |
|
| Reduced motivation 7 days Change |
|
| Reduced motivation 14 days Change |
|
| Reduced activity 3 days Change |
|
| Reduced activity 7 days Change |
|
| Reduced activity 14 days Change |
|
| 0.8781 |
P-value for General fatigue 7 days Change. Model: Change from baseline=Baseline, Visit, Treatment, Treatment*Visit |
| Superiority |
| MMRM | 0.226 | P-value for General fatigue 14 days Change. Model: Change from baseline=Baseline, Visit, Treatment, Treatment*Visit | Superiority |
| MMRM | 0.2158 | P-value for Mental fatigue 3 days Change. Model: Change from baseline=Baseline, Visit, Treatment, Treatment*Visit | Superiority |
| MMRM | 0.0081 | P-value for Mental fatigue 7 days Change. Model: Change from baseline=Baseline, Visit, Treatment, Treatment*Visit | Superiority |
| MMRM | 0.6768 | P-value for Mental fatigue 14 days Change. Model: Change from baseline=Baseline, Visit, Treatment, Treatment*Visit | Superiority |
| MMRM | 0.0076 | P-value for Physical fatigue 3 days Change. Model: Change from baseline=Baseline, Visit, Treatment, Treatment*Visit | Superiority |
| MMRM | 0.0858 | P-value for Physical fatigue 7 days Change. Model: Change from baseline=Baseline, Visit, Treatment, Treatment*Visit | Superiority |
| MMRM | 0.2065 | P-value for Physical fatigue 14 days Change. Model: Change from baseline=Baseline, Visit, Treatment, Treatment*Visit | Superiority |
| MMRM | 0.9712 | P-value for Reduced motivation 3 days Change. Model: Change from baseline=Baseline, Visit, Treatment, Treatment*Visit | Superiority |
| MMRM | 0.7572 | P-value for Reduced motivation 7 days Change. Model: Change from baseline=Baseline, Visit, Treatment, Treatment*Visit | Superiority |
| MMRM | 0.0588 | P-value for Reduced motivation 14 days Change. Model: Change from baseline=Baseline, Visit, Treatment, Treatment*Visit | Superiority |
| MMRM | 0.1857 | P-value for Reduced activity 3 days Change. Model: Change from baseline=Baseline, Visit, Treatment, Treatment*Visit | Superiority |
| MMRM | 0.9225 | P-value for Reduced activity 7 days Change. Model: Change from baseline=Baseline, Visit, Treatment, Treatment*Visit | Superiority |
| MMRM | 0.0414 | P-value for Reduced activity 14 days Change. Model: Change from baseline=Baseline, Visit, Treatment, Treatment*Visit | Superiority |
| Psychosocial function 14 days Change |
|
| 0.2521 |
P-value for Psychosocial function 7 days Change. Model: Change from baseline=Baseline, Visit, Treatment, Treatment*Visit |
| Superiority |
| MMRM | 0.6635 | P-value for Psychosocial function 14 days Change. Model: Change from baseline=Baseline, Visit, Treatment, Treatment*Visit | Superiority |
| Anhedonia 14 days Change |
|
| 0.0248 |
P-value for Anhedonia function 7 days Change. Model: Change from baseline=Baseline, Visit, Treatment, Treatment*Visit |
| Superiority |
| MMRM | 0.0199 | P-value for Anhedonia 14 days Change. Model: Change from baseline=Baseline, Visit, Treatment, Treatment*Visit | Superiority |