Actively Recruiting
Leucine as a Probe of Kynurenine-Induced Glutamate and Neural Circuit Dysfunction in Midlife Depression
Led by Emory University · Updated on 2025-04-24
75
Participants Needed
1
Research Sites
52 weeks
Total Duration
On this page
Sponsors
E
Emory University
Lead Sponsor
N
National Institute of Mental Health (NIMH)
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are investigating the effects of a 6-week leucine challenge on brain chemistry, connectivity, and behavior in middle-aged adults with major depression. The study focuses on symptoms like loss of pleasure and slowed movements, which may indicate harder-to-treat depression and increased dementia risk. It explores how inflammation and the kynurenine pathway might contribute to depression by producing brain-toxic substances. Leucine, a nutrient, may block these toxins and improve brain function, but its effects in humans are not yet known. Participants will be randomly assigned to receive either L-leucine or L-lysine supplements daily for 6 weeks. L-leucine is given at 4.31 grams per day and aims to inhibit harmful kynurenine uptake in the brain, while L-lysine at 6 grams per day serves as an active comparator to control for general protein synthesis effects. Both supplements are taken orally. The study uses a triple-blind design to compare these two groups. During the study, participants will undergo brain scans and assessments at baseline, week 1, and week 6 to measure changes in glutamate levels, brain connectivity, effort, anhedonia, and psychomotor slowing. Blood tests and questionnaires will monitor inflammation and depression severity. Safety and adherence will be tracked throughout, with the total participation lasting 6 weeks. This research could help understand how inflammation affects depression and explore new treatment avenues.
CONDITIONS
Brief Title
Leucine in Midlife Depression
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Able and willing to provide informed consent
- Diagnosis of major depression per Structured Interview for DSM-V (SCID-V)
- Moderate to severe depression with Inventory of Depressive Symptoms - Self Reported (IDS-SR) score greater than 34
- Snaith-Hamilton Pleasure Scale (SHAPS) score greater than 30 on the 0-56 scale
- Body mass index (BMI) between 20 and 35 kg/m2
- Plasma C-reactive protein (CRP) greater than 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 unless exempt due to sex or reproductive status
You will not qualify if you...
- History of maple syrup urine disease
- Risk of hypoglycemia or unstable diabetes
- History of vitamin B6 deficiency
- Current use of calcium supplements (for lysine group)
- History of renal or gall stones
- Cognitive impairment (MMSE score less than 28)
- Lifetime diagnosis of psychotic disorders
- Current mania or hypomania
- Substance use disorder in the last 6 months
- Active suicidal ideation or recent suicide attempts
- Psychiatric hospitalization in the past year
- Scores greater than 3 on Columbia Suicide Severity Rating Scale
- Binge eating unrelated to mood symptoms
- Primary diagnosis of severe anxiety disorders, PTSD, obsessive-compulsive disorders, or significant personality disorders
- Developmental disorders such as ADHD
- Use of immune-active medications, antibiotics, immunizations, or steroids within specified recent time frames
- Use of psychotropic medications within the last 4 weeks (8 weeks for fluoxetine)
- Daily use of sedative-hypnotics, benzodiazepines, or opiates
- Unstable medical disorders
- Lifetime diagnosis or treatment of cancers (except basal cell carcinoma)
- Lifetime diagnosis or treatment of autoimmune disorders
- Lifetime exposure to chemotherapy
- MRI contraindications due to metal
- Current antidepressant or dopamine supplement treatments
- Pregnancy, children, prisoners, or inability to consent
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - 6 weeks
Participants take either leucine or lysine supplements daily to assess their effects on depression and brain function.
3 visits at Baseline, Week 1, and Week 6
Trial Site Locations
Total: 1 location
1
Emory University Hospital
Atlanta, Georgia, United States, 30322
Actively Recruiting
Research Team
E
Ebrahim Haroon, MD
D
Diana Beltran, BS
How is the study designed?
Study Type
INTERVENTIONAL
Masking
TRIPLE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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