Leucine in Midlife Depression
NCT Number: NCT06580145
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Major Depression
Sponsor: Emory University
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 75
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: TRIPLE (PARTICIPANT, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-09
Completion Date: 2029-07

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.

Primary Outcome Measures: 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., Baseline, Week 1, Week 6
Secondary Outcome Measures: 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., 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, 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., 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., 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., Baseline, Week 1, Week 6