Back to resultsRapid Antidepressant Effects of Leucine
Primary Purpose
Major Depressive Disorder
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
L-Leucine
Maltodextrin
Sponsored by
About this trial
This is an interventional treatment trial for Major Depressive Disorder focused on measuring Antidepressant, Inflammation, Biomarker, Depression, Treatment Resistant Depression, Leucine
Eligibility Criteria
Inclusion Criteria:
- Current primary diagnosis of nonpsychotic major depressive disorder.
- Stable antidepressant dose of no more than one antidepressant medication for 4 weeks and no anticipated changes during the study period.
- Stable doses of all concomitant medications for over 6 weeks.
- No more than two failed antidepressant trials of adequate dose and duration, as defined by ATRQ, in the current episode.
Exclusion Criteria:
- Psychiatric co-morbidity posing safety risk.
- Pregnant or breastfeeding or plan to become pregnant over the ensuing 2 months following study entry or are sexually active and not using adequate contraception
- Exclusionary psychiatric conditions (such as substance dependence in the last 6 months, substance abuse in the last 2 months, or lifetime history of psychotic disorders.
- Unstable or terminal general medical condition (GMC).
- Concomitant medications that interact with L-leucine (e.g. sildenafil).
- Vagus nerve stimulation, ECT, or rTMS, or other somatic antidepressant treatment during current episode
- Inadequately controlled hypothyroidism.
- Therapy that is depression specific, such as CBT or Interpersonal Psychotherapy of Depression.
- Hypersensitivity to L-leucine
- Have Maple Syrup Urine Disease.
Sites / Locations
- University of Texas Southwestern Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
L-leucine
Maltodextrin
Arm Description
4 gm L-leucine by mouth twice daily for two weeks
4 gm maltodextrin by mouth twice daily for two weeks
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT03079297
First Posted
March 4, 2017
Last Updated
December 29, 2022
Sponsor
University of Texas Southwestern Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT03079297
Brief Title
Rapid Antidepressant Effects of Leucine
Official Title
A Pilot Double-Blind Randomized Placebo-Controlled Crossover Study to Investigate Rapid Antidepressant Effects of Leucine
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Terminated
Why Stopped
Covid-19
Study Start Date
March 9, 2017 (Actual)
Primary Completion Date
October 4, 2021 (Actual)
Study Completion Date
October 4, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Texas Southwestern Medical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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).
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder
Keywords
Antidepressant, Inflammation, Biomarker, Depression, Treatment Resistant Depression, Leucine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
L-leucine
Arm Type
Experimental
Arm Description
4 gm L-leucine by mouth twice daily for two weeks
Arm Title
Maltodextrin
Arm Type
Placebo Comparator
Arm Description
4 gm maltodextrin by mouth twice daily for two weeks
Intervention Type
Drug
Intervention Name(s)
L-Leucine
Other Intervention Name(s)
Leucine
Intervention Description
L-leucine is an essential amino acid which will be provided as an effervescent powder mixture to participants.
Intervention Type
Other
Intervention Name(s)
Maltodextrin
Other Intervention Name(s)
Placebo
Intervention Description
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
Primary Outcome Measure Information:
Title
Change in QIDS-SR From Baseline at 14 Days
Description
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.
Time Frame
Baseline to 14 days
Secondary Outcome Measure Information:
Title
Percentage of MDD Patients With 50% or Greater Reduction in Depression Severity After 14 Days of LEU and PBO Treatments.
Description
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.
Time Frame
Baseline to 14 days
Title
Percentage of MDD Patients With QIDS-SR Score Less Than or Equal to 5 at 14 Days of LEU and PBO Treatments.
Description
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.
Time Frame
14 days
Title
Rates of Adverse Effects After 3 Days, 7 Days and 14 Days of LEU and PBO Treatments.
Description
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.
Time Frame
Baseline to 3 days, 7 days, and 14 days
Title
Change in Fatigue Symptoms From Baseline After 3, 7, and 14 Days of LEU and PBO Treatments Measured With Multidimensional Fatigue Inventory.
Description
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.
Time Frame
Baseline to 3 days, 7 days, and 14 days
Title
Change in Psychosocial Function From Baseline After 3, 7, and 14 Days of LEU and PBO Treatments Measured Using Work and Social Adjustment Scale.
Description
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.
Time Frame
Baseline to 3 days, 7 days, and 14 days
Title
Change in Anhedonia From Baseline After 3, 7, and 14 Days of LEU and PBO Treatments Measured Using Snaith-Hamilton Pleasure Scale (SHAPS)
Description
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.
Time Frame
Baseline to 3 days, 7 days, and 14 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Current primary diagnosis of nonpsychotic major depressive disorder.
Stable antidepressant dose of no more than one antidepressant medication for 4 weeks and no anticipated changes during the study period.
Stable doses of all concomitant medications for over 6 weeks.
No more than two failed antidepressant trials of adequate dose and duration, as defined by ATRQ, in the current episode.
Exclusion Criteria:
Psychiatric co-morbidity posing safety risk.
Pregnant or breastfeeding or plan to become pregnant over the ensuing 2 months following study entry or are sexually active and not using adequate contraception
Exclusionary psychiatric conditions (such as substance dependence in the last 6 months, substance abuse in the last 2 months, or lifetime history of psychotic disorders.
Unstable or terminal general medical condition (GMC).
Concomitant medications that interact with L-leucine (e.g. sildenafil).
Vagus nerve stimulation, ECT, or rTMS, or other somatic antidepressant treatment during current episode
Inadequately controlled hypothyroidism.
Therapy that is depression specific, such as CBT or Interpersonal Psychotherapy of Depression.
Hypersensitivity to L-leucine
Have Maple Syrup Urine Disease.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Madhukar H Trivedi, M.D.
Organizational Affiliation
UT Southwestern Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
18073775
Citation
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.
Results Reference
background
PubMed Identifier
28187400
Citation
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.
Results Reference
background
PubMed Identifier
18678792
Citation
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.
Results Reference
background
PubMed Identifier
16554525
Citation
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.
Results Reference
background
PubMed Identifier
16554526
Citation
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.
Results Reference
background
Learn more about this trial
Rapid Antidepressant Effects of Leucine
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