AzTrials
AzTrials

Major DepressionPhase 2NCT06580145

Leucine in Midlife Depression

A Phase 2 study testing L-leucine and L-lysine in people with Major Depression, run by Emory University at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 35 to 65 years
Conditions the study is for
Major Depression
What is being tested?
L-leucine and L-lysine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
75 participants
Where
1 siteUnited States
Study dates
1 Feb 2025to Jun 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 35 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 15Show fewer
  • 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)

Who cannot join

  • 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
Show all 48Show fewer
  • 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.
  • 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).
  • 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.
  • 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.
  • 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):
  • Stabilized medications are allowed if maintained at the same dose during the trial.
  • Multiple recent changes in concomitant medications reviewed by the study PI
  • Population
  • Pregnant women.
  • Children.
  • Prisoners.
  • Individuals unable to consent

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Ebrahim Haroon, MD contact

(404) 727-8229

eharoon@emory.edu

Diana Beltran, BS contact

404-712-7686

djbeltr@emory.edu

United States1 site, 1 recruiting

  • Emory University Hospital

    Atlanta, Georgia, 30322

    Ebrahim Haroon, MD, 404-712-2890, eharoon@emory.edu

    Recruiting

Other trials in United States

About this study

Official title: 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.

Read the detailed description

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.

Being tested
L-leucine, L-lysine
Keywords
Major Depression, Kynurenine (KYN) pathway, Leucine in Midlife Depression, inflammation
Medical subject headings
Depressive Disorder, Major, Inflammation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • L-leucineDrug

    Also called Leucine

    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.

  • L-lysineDrug

    Also called Lysine

    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

Study groups in NCT06580145
Study groupRoleWhat they receive
L-leucineExperimentalNot described
Receives: Drug: L-leucine
L-lysineActive comparatorNot described
Receives: Drug: L-lysine

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline, Week 1, Week 6

Secondary outcomes (5)

  1. 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.

    Measured: Baseline, Week 1, Week 6

  2. 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

    Measured: Baseline, Week 1, Week 6

  3. 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.

    Measured: Baseline, Week 1, Week 6

  4. 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.

    Measured: Baseline, Week 1, Week 6

  5. 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.

    Measured: Baseline, Week 1, Week 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Aug 2024
  2. Study start1 Feb 2025
  3. Primary completionJun 2028 (estimated)
  4. Study completionJun 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
75 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06580145
Sponsor's protocol ID
STUDY00006751
Other IDs
R01MH132059
Status last verified
Sep 2026
First submitted
29 Aug 2024
Last updated
11 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: PI will share individual de-identified participant data, including data dictionaries according to institutional, state, and Federal regulations. This aligns with Emory University\'s commitment to transparency and compliance with NIH guidelines, which support making research data widely available while ensuring participant confidentiality.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing L-leucine and L-lysine in people with Major Depression, run by Emory University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 48 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 11 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Ebrahim Haroon, MD ((404) 727-8229, eharoon@emory.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Glutamate (time frame: Baseline, Week 1, Week 6). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06580145.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in