Tests leucine and lysine in adults with midlife depression

Trial details

Who runs it

Emory University

Trial code

NCT06580145

Record updated

11 September 2026

Original description

The study aims to investigate the effects of a 6-week leucine challenge on brain chemistry, connectivity, and behavior in people with midlife depression.Read full original descriptionShow less

Leucine as a Probe of Kynurenine-Induced Glutamate and Neural Circuit Dysfunction in Midlife Depression

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.

Inclusion: 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).

Exclusion: Concomitant medications:; Immune-active medications (e.g., non-steroidal anti-inflammatory agents); Antibiotics and immunizations in the past 2 weeks; Topical or inhaled steroids within the past week; Oral/parenteral steroids in the last 6 months; Supplements that impact the immune system (e.g., omega-3, probiotics) within the past 2 weeks; Psychotropic medications within the last 4 weeks (8 weeks for fluoxetine); Daily use of sedative-hypnotics, benzodiazepines, and opiates; Concomitant Treatment for Depression:; -- Treatments with antidepressant medications or those with antidepressant effects (dopamine supplements); Treatment for General Medical Conditions (GMCs):; Stabilized medications are allowed if maintained at the same dose during the trial; Multiple recent changes in concomitant medications reviewed by the study PI; Leucine-Specific:; History of maple syrup urine disease; Risk of hypoglycemia (unstable diabetes); History of vitamin B6 deficiency, relative; 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; Suicide attempts within the last five years; Scores >3 on the Columbia Suicide Severity Rating Scale (C-SSRS); Binge eating in the absence of mood symptoms increases; Primary diagnosis of severe DSM-V79 anxiety disorders; Primary diagnosis of DSM-V PTSD (if severity exceeds major depression); Primary diagnosis of DSM-V obsessive-compulsive disorders; Significant personality disorders with multiple hospitalizations or suicide attempts; Developmental disorders (e.g., ADHD); Medical Disorders:; Unstable medical disorders (frequent provider or medication changes); Lifetime diagnosis/treatment of cancers (excluding basal cell carcinoma); Lifetime diagnosis/treatment of autoimmune disorders; Lifetime exposure to chemotherapeutic agents; Lysine-Specific:; On calcium supplements, relative; History of renal/gall stones (could cleared by a primary care provider); MRI Considerations:; -- Location and quantity of metallic objects safe to MR; Population; Pregnant women; Children; Prisoners; Individuals unable to consent.

ClinicalTrials.gov NCT06580145