A Phase 2 interventional study of L-leucine and L-lysine in Major Depression, sponsored by Emory University. Recruiting at 1 site in United States. Open to participants aged 35 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-09-11.
Sponsored by Emory University · Phase 2, Interventional, and Treatment
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.
Major depression is a common and serious mental health condition that can severely impact a person's quality of life. Some symptoms, like loss of pleasure in activities and slowed movements, may be signs that the depression will be harder to treat. These symptoms are also linked to a higher risk of dementia later in life.
Scientists think that long-term, low-level inflammation in the body may contribute to depression, especially in middle-aged adults. This inflammation may affect areas of the brain involved in feeling good and controlling movement.
One way inflammation might lead to depression is through a process in the body called the kynurenine pathway. When activated by inflammation, this pathway can produce substances that are toxic to brain cells. These toxins can disrupt how brain cells communicate and function.
Leucine, a nutrient found in some foods, may help block these toxic substances from entering the brain. While animal studies have shown promise, we do yet know if leucine can help humans with depression.
To find out, researchers are planning a 6-week study in middle-aged adults with depression and signs of inflammation. Half the participants will take leucine supplements, while the other half will take a different supplement (lysine) for comparison. The study will use brain scans and symptom assessments to see if leucine improves brain function and reduces depression.
If successful, this research could point to new ways to treat depression, especially in cases that do not respond well to current treatments. It may also help reduce the risk of dementia in people with depression. This study is an important step in understanding how inflammation affects mental health and in developing new treatments to help people feel better.
3,041 studies on the registry are indexed under Depressive Disorder, Major; 588 are open to participants now.
This study's planned enrollment of 75 is close to the median of 79 across 2,530 interventional studies indexed under Depressive Disorder, Major.
Browse Depressive Disorder, Major studies →Emory University is the lead sponsor of 1,405 studies on the registry; 225 are open to participants now.
Of its 237 completed or terminated interventional studies of FDA-regulated products, 178 (75%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Willingness to adopt measures. Persons exempt from contraception requirements are:
Persons assigned female at birth who:
Exclusion Criteria:
Leucine-Specific:
Lysine-Specific:
Cognitive:
--Cognitive impairment ( score \<28)
Psychiatric Disorders:
Concomitant medications:
Medical Disorders:
MRI Considerations:
-- Location and quantity of metallic objects safe to MR
Concomitant Treatment for Depression:
-- Treatments with antidepressant medications or those with antidepressant effects (dopamine supplements).
Treatment for General Medical Conditions (GMCs):
Population
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
MMSE and MoCA
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Drug: L-leucine
Drug: L-lysine
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-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
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.
Time frame: Baseline, Week 1, Week 6
Change in blood oxygen level dependent (BOLD) oscillatory coherence
Changes in blood oxygen level dependent (BOLD) oscillatory coherence, measured by regional homogeneity (ReHo) in the basal ganglia and its functional connectivity to the dorsomedial prefrontal cortex (dmPFC) between the two groups.
Time frame: Baseline, Week 1, Week 6
Changes in effort discontinuation ability
The Effort Expenditure for Rewards Task (EEfRT) will be utilized measure to assess motivational deficits related to anhedonia. The EEfRT is a computerized task where participants choose between easy (low-effort, low-reward) and hard (high-effort, high-reward) tasks, with varying probabilities of reward receipt. An increase in the proportion of high-effort choices over time would indicate improved motivation and potentially increased willingness to expend effort to achieve rewards
Time frame: Baseline, Week 1, Week 6
Change in anhedonia
The Snaith-Hamilton Pleasure Scale - Clinician Version (SHAPS-C) will be administered by trained clinicians at baseline and specified follow-up visits as outlined in the Schedule of Assessments. The SHAPS-C is a 14-item scale measuring consummatory (enjoyment) aspects of anhedonia. Lower scores indicate a greater capacity for pleasure, while higher scores reflect more severe anhedonia. An alternate version of SHAPS (SHAPS) is available as a self-rated version, where participants will rate themselves on a scale. The self-ratings are added to generate a total score, which has similar characteristics as those for SHAPS-C.
Time frame: Baseline, Week 1, Week 6
Change in MRS myo-inositol
Change in MRS myo-inositol (mI) in the basal ganglia 6 between the leucine and lysine groups will be assessed.
Time frame: Baseline, Week 1, Week 6
Changes in psychomotor slowing
Psychomotor slowing will be assessed as a tertiary outcome using neurocognitive tests. These include the Finger Tapping Task (FTT), Simple and Choice Reaction Time tasks from the Cambridge Automated Neuropsychological Test Assessment Battery (CANTAB), Digit Symbol Substitution Test (DSST), and Trail Making Tests A and B. The FTT measures pure motor function, while the Reaction Time tasks on CANTAB assess the speed and accuracy of responses. The DSST evaluates information processing speed, and the Trail Making Tests assess cognitive flexibility and task-switching abilities. Improved performance on these tasks, indicated by faster completion times and increased accuracy, would suggest a reduction in psychomotor slowing.
Time frame: Baseline, Week 1, Week 6
Plan to share: Yes — PI will share individual de-identified participant data, including data dictionaries according to institutional, state, and Federal regulations. This aligns with Emory University\&#39;s commitment to transparency and compliance with NIH guidelines, which support making research data widely available while ensuring participant confidentiality.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, 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\&#39;s and NIH\&#39;s data-sharing policies
Data sharing details ↗ · nda.nih.gov
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Studies of the drug tested here: Leucine