Leucine in Midlife Depression
ConditionMajor Depression
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age35-65
SponsorEmory University
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
History of maple syrup urine disease
Risk of hypoglycemia (unstable diabetes)
History of vitamin B6 deficiency, relative
On calcium supplements, relative
Trial design
Design model
Parallel
Treatments tested in this trial
L-leucine
DrugL-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-lysine
DrugL-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
Treatment groups
75 Participants
are divided into 2 treatment groupsGroup A: L-leucineExperimental treatment 1 intervention
Group B: L-lysineActive comparator 1 intervention
Trial outcomes
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.
Time frame
Baseline, Week 1, Week 6Secondary outcomes
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.
Time frame
Baseline, Week 1, Week 62
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 63
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 64
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 6Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Emory University
Lead sponsor
National Institute of Mental Health (NIMH)
Collaborator
Source ClinicalTrials.gov