Rapid Antidepressant Effects of Leucine

NCT03079297 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: STU 082016-037
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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).

Conditions

Major Depressive Disorder

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline to 14 days

Secondary Outcomes (6)

• Percentage of MDD Patients With 50% or Greater Reduction in Depression Severity After 14 Days of LEU and PBO Treatments.

  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.

  14 days

• Rates of Adverse Effects After 3 Days, 7 Days and 14 Days of LEU and PBO Treatments.

  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.

  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.

  Baseline to 3 days, 7 days, and 14 days

Study Arms (2)

L-leucine

EXPERIMENTAL

4 gm L-leucine by mouth twice daily for two weeks

Drug: L-Leucine

Maltodextrin

PLACEBO COMPARATOR

4 gm maltodextrin by mouth twice daily for two weeks

Other: Maltodextrin

Interventions

L-Leucine DRUG

L-leucine is an essential amino acid which will be provided as an effervescent powder mixture to participants.

Also known as: Leucine

L-leucine

Maltodextrin OTHER

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

Also known as: Placebo

Maltodextrin

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Related Publications (5)

• 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.

  PMID: 18073775 BACKGROUND

• 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.

  PMID: 28187400 BACKGROUND

• 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.

  PMID: 18678792 BACKGROUND

• 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.

  PMID: 16554525 BACKGROUND

• 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.

  PMID: 16554526 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Major; Inflammation; Depression; Depressive Disorder, Treatment-Resistant

Interventions

Leucine; maltodextrin

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Results Point of Contact

• Title: Maria Monastirsky
• Organization: University of Texas Southwestern

Maria.Monastirsky@utsouthwestern.edu

214-648-0174

Study Officials

• Madhukar H Trivedi, M.D.

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: March 4, 2017
• First Posted: March 14, 2017
• Study Start: March 9, 2017
• Primary Completion: October 4, 2021
• Study Completion: October 4, 2021
• Last Updated: January 26, 2023
• Results First Posted: January 26, 2023

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)