Clinical trial NCT03079297: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Major Depressive Disorder
Keywords: Antidepressant
Inflammation
Biomarker
Depression
Treatment Resistant Depression
Leucine
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2017-03-14
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change in QIDS-SR From Baseline at 14 Days
timeFrame: Baseline to 14 days
Secondary outcomes:
measure: Percentage of MDD Patients With 50% or Greater Reduction in Depression Severity After 14 Days of LEU and PBO Treatments.
timeFrame: Baseline to 14 days
measure: Percentage of MDD Patients With QIDS-SR Score Less Than or Equal to 5 at 14 Days of LEU and PBO Treatments.
timeFrame: 14 days
measure: Rates of Adverse Effects After 3 Days, 7 Days and 14 Days of LEU and PBO Treatments.
timeFrame: Baseline to 3 days, 7 days, and 14 days
measure: Change in Fatigue Symptoms From Baseline After 3, 7, and 14 Days of LEU and PBO Treatments Measured With Multidimensional Fatigue Inventory.
timeFrame: Baseline to 3 days, 7 days, and 14 days
measure: Change in Psychosocial Function From Baseline After 3, 7, and 14 Days of LEU and PBO Treatments Measured Using Work and Social Adjustment Scale.
timeFrame: Baseline to 3 days, 7 days, and 14 days
measure: Change in Anhedonia From Baseline After 3, 7, and 14 Days of LEU and PBO Treatments Measured Using Snaith-Hamilton Pleasure Scale (SHAPS)
timeFrame: Baseline to 3 days, 7 days, and 14 days
Other outcomes:
Locations:
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
Study officials:
affiliation: UT Southwestern Medical Center
name: Madhukar H Trivedi, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.