Rapid Antidepressant Effects of Leucine

• ClinicalTrials.gov Identifier: NCT03079297
• Recruitment Status: Suspended
• First Posted: March 14, 2017
• Last Update Posted: March 9, 2021
• Sponsor: University of Texas Southwestern Medical Center
• Information provided by (Responsible Party): Madhukar H. Trivedi, MD, University of Texas Southwestern Medical Center

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).

Condition or disease	Intervention/treatment	Phase
Major Depressive Disorder	Drug: L-Leucine; Other: Maltodextrin	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Pilot Double-Blind Randomized Placebo-Controlled Crossover Study to Investigate Rapid Antidepressant Effects of Leucine
• Actual Study Start Date: March 9, 2017
• Estimated Primary Completion Date: March 1, 2022
• Estimated Study Completion Date: June 30, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: L-leucine; 4 gm L-leucine by mouth twice daily for two weeks	Drug: L-Leucine; L-leucine is an essential amino acid which will be provided as an effervescent powder mixture to participants.; Other Name: Leucine
Placebo Comparator: Maltodextrin; 4 gm maltodextrin by mouth twice daily for two weeks	Other: Maltodextrin; 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; Other Name: Placebo

Outcome Measures

Primary Outcome Measures :

1. Comparison of reduction in QIDS-SR after 14 days of treatment with L-leucine (LEU) and placebo (PBO) in MDD patients. [ Time Frame: 14 days ]
   QIDS-SR measures self-reported depression severity

Secondary Outcome Measures :

1. Percentage of MDD patients with 50% or greater reduction in depression severity after 14 days of LEU and PBO treatments. [ Time Frame: Baseline to 14 days ]
   Response criteria defined based on QIDS-SR score at baseline and 14 days after treatment initiation
2. Percentage of MDD patients with QIDS-SR score less than or equal to 5 at 14 days of LEU and PBO treatments. [ Time Frame: 14 days ]
   Remission operationalized as QIDS-SR <=5
3. Rates of adverse effects after 3 days, 7 days and 14 days of LEU and PBO treatments. [ Time Frame: 3 days, 7 days, and 14 days ]
   Adverse effect burden will be measured with Frequency Intensity and Burden of Side-effect rating scale (FIBSER)
4. Change in fatigue symptoms from baseline after 3, 7, and 14 days of LEU and PBO treatments measured with Multidimensional fatigue inventory. [ Time Frame: 3 days, 7 days, and 14 days ]
   Fatigue will be measured with Multidimensional fatigue inventory
5. Change in psychosocial function from baseline after 3, 7, and 14 days of LEU and PBO treatments measured using Work and Social Adjustment Scale. [ Time Frame: 3 days, 7 days, and 14 days ]
   Psychosocial function will be measured using Work and Social Adjustment Scale
6. Change in anhedonia from baseline after 3, 7, and 14 days of LEU and PBO treatments measured using Snaith-Hamilton Pleasure Scale (SHAPS) [ Time Frame: 3 days, 7 days, and 14 days ]
   Anhedonia will be measured using Snaith-Hamilton Pleasure Scale (SHAPS)

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 64 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Texas

University of Texas Southwestern Medical Center

Dallas, Texas, United States, 75390

Sponsors and Collaborators

University of Texas Southwestern Medical Center

Investigators

• Principal Investigator: Madhukar H Trivedi, M.D.; UT Southwestern Medical Center

More Information

Publications:

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. Review.

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.

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.

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.

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.

• Responsible Party: Madhukar H. Trivedi, MD, MD, University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT03079297
• Other Study ID Numbers: STU 082016-037
• First Posted: March 14, 2017
• Last Update Posted: March 9, 2021
• Last Verified: March 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Madhukar H. Trivedi, MD, University of Texas Southwestern Medical Center:

Antidepressant; Inflammation; Biomarker; Depression; Treatment Resistant Depression; Leucine

Additional relevant MeSH terms:

Depressive Disorder; Depressive Disorder, Major; Mood Disorders; Mental Disorders