Leucine in Midlife Depression

NCT06580145 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: STUDY00006751R01MH132059
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

The study aims to investigate the effects of a 6-week leucine challenge on brain chemistry, connectivity, and behavior in people with midlife depression. The researchers will compare the leucine and an active comparator arm (lysine) for 6 weeks.

Conditions

Major Depression

Keywords

Major Depression; Kynurenine (KYN) pathway; Leucine in Midlife Depression; inflammation

Outcome Measures

Primary Outcomes (1)

• Change in Glutamate

  Change in glutamate measured by magnetic resonance spectroscopy (MRS) in the basal ganglia in the leucine challenged group compared with the lysine-challenged group.

  Baseline, Week 1, Week 6

Secondary Outcomes (5)

• Change in blood oxygen level dependent (BOLD) oscillatory coherence

  Baseline, Week 1, Week 6

• Changes in effort discontinuation ability

  Baseline, Week 1, Week 6

• Change in anhedonia

  Baseline, Week 1, Week 6

• Change in MRS myo-inositol

  Baseline, Week 1, Week 6

• Changes in psychomotor slowing

  Baseline, Week 1, Week 6

Study Arms (2)

L-leucine

EXPERIMENTAL

Drug: L-leucine

L-lysine

ACTIVE COMPARATOR

Drug: L-lysine

Interventions

L-leucine DRUG

L-leucine is an essential amino acid used to competitively inhibit kynurenine uptake into the brain via the large neutral amino acid transporter (LAT1). The proposed dose for L-leucine is 4.31 g/day, administered orally.

Also known as: Leucine

L-leucine

L-lysine DRUG

L-lysine monohydrochloride is also an essential amino acid. It serves as an active comparator to control for general effects on brain protein synthesis and enters the brain through separate cationic amino acid transporters. The proposed dose for L-lysine is 6 g/day, administered orally

Also known as: Lysine

L-lysine

Eligibility Criteria

• Age: 35 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able and willing to provide informed consent
• Diagnosis of major depression per Structured Interview for DSM-V (SCID-V)
• Moderate to severe depression- Inventory of Depressive Symptoms - Self Reported (IDS-SR score \>34).
• SHAPS score \>30 on the 0-56 scale
• Body mass index (BMI) between 20-35 kg/m2
• Plasma CRP \>1 mg/L
• No contraindications to MRI
• Availability of friends or family for transportation after lumbar puncture procedure
• Clinically significant findings on EKG
• Patient Health Questionnaire (PHQ-9) score greater than 10
• Willingness to adopt contraceptive measures. Persons exempt from contraception requirements are:
• Persons assigned male at birth
• Persons assigned female at birth who:
• have undergone a hysterectomy or bilateral oophorectomy; or
• have been naturally postmenopausal for at least 24 consecutive months (i.e., has NOT had menses at any time in the preceding 24 consecutive months)

You may not qualify if:

• Leucine-Specific:
• History of maple syrup urine disease
• Risk of hypoglycemia (unstable diabetes)
• History of vitamin B6 deficiency, relative
• Lysine-Specific:
• On calcium supplements, relative
• History of renal/gall stones (could cleared by a primary care provider)
• Cognitive:
• Cognitive impairment (MMSE score \<28)
• Psychiatric Disorders:
• Lifetime diagnosis of psychotic disorders.
• Current mania/hypomania.
• Substance use disorder in the last 6 months.
• Active suicidal ideation:
• Psychiatric hospitalization in the past year.

Sponsors & Collaborators

• Emory University: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Emory University Hospital

Atlanta, Georgia, 30322, United States

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major; Inflammation

Interventions

Leucine; Lysine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Ebrahim Haroon, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ebrahim Haroon, MD

CONTACT

(404) 727-8229; eharoon@emory.edu

Diana Beltran, BS

CONTACT

404-712-7686; djbeltr@emory.edu

Study Design

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

Study Record Dates

• First Submitted: August 29, 2024
• First Posted: August 30, 2024
• Study Start: February 1, 2025
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2029
• Last Updated: April 24, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: The data will be available starting at publication and remain accessible for a period specified in our Data Management and Sharing Plan (DMSP), as required by NIH, institutional, and state regulations. This typically means the data will be available for several years post-publication to facilitate ongoing research.
• Access Criteria: Data will be shared with qualified researchers who submit an approved research proposal. PI requires that the researchers sign a Data Transfer Agreement (DTA) to ensure compliance with ethical and legal standards. The team will use a secure data repository (NIH DataArchive) to share the data, as specified in our DMSP. This ensures that data is accessible while maintaining security and compliance with Emory\'s and NIH\'s data-sharing policies

Locations

US (1)