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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
16
L-leucine is an essential amino acid which will be provided as an effervescent powder mixture to participants.
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
University of Texas Southwestern Medical Center
Dallas, Texas, United States
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.
Time frame: Baseline to 14 days
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.
Time frame: 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.
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Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline to 3 days, 7 days, and 14 days