Rapid Antidepressant Effects of Leucine

Sponsor

University of Texas Southwestern Medical Center (Other)

Overall Status

Terminated

CT.gov ID

NCT03079297

Collaborator

(none)

Enrollment

Location

Arms

54.9

Actual Duration (Months)

0.3

Patients Per Site Per Month

Study Details

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

Actual Enrollment :

16 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 :

Mar 9, 2017

Actual Primary Completion Date :

Oct 4, 2021

Actual Study Completion Date :

Oct 4, 2021

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 Names: 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 Names: Placebo

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 Names:

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 Names:

Placebo

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 64 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.