- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03557684
Leucine for Depression Study (L-DEP)
An Experimental Treatment Approach for Inflammation-Induced Depression
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Early Phase 1
Contacts and Locations
Study Locations
-
-
California
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Los Angeles, California, United States, 90095
- UCLA Cousins Center for Psychoneuroimmunology
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
Participants will be required to be in good general health (as evaluated during the phone and in-person screening sessions) and aged 18 to 65 years.
Exclusion Criteria:
Following a structured telephone interview, prospective participants with the following conditions will not advance to the in-person screening session: presence of chronic mental or physical illness, history of allergies, autoimmune, liver, or other severe chronic diseases, current use of prescription medications such as steroids, NSAIDs, immune modifying drugs, opioid analgesics, and psychotropics, or previous history of fainting during blood draws. These inclusion and exclusion criteria will be examined in detail and confirmed in the in-person screening session by the study physician. Furthermore, any participant who has any of the following conditions will be ineligible for the study. Medical Conditions: (1) presence of co-morbid medical conditions not limited to but including maple syrup urine disease (a contraindication to leucine treatment), cardiovascular (e.g., history of acute coronary event, stroke) and neurological diseases (e.g., Parkinson's disease), as well as pain disorders; (2) presence of co-morbid inflammatory disorders such as rheumatoid arthritis or other autoimmune disorders; (3) presence of an uncontrolled medical condition that is deemed by the investigators to interfere with the proposed study procedures, or to put the study participant at undue risk; (4) presence of chronic infection, which may elevate proinflammatory cytokines; (5) presence of an acute infectious illness in the two weeks prior to the screening session. Psychiatric Disorders: (6) an Axis I psychiatric disorder as determined by the Research Version of the Structured Clinical Interview for DSM-5 (SCID-5-RV) including a current major depressive disorder (a prior history of depression is not an exclusion criterion, which will be considered for a pre-planned sensitivity analysis); (7) lifetime history of suicide attempt or inpatient psychiatric admission; (8) current suicidal ideation assessed by the Columbia Suicide Severity Rating Scale (C-SSRS); (9) current depressive symptoms assessed by the PHQ-9 (≥ 5)). Medication and Substance Use: (10) current and/or past regular use of hormone-containing medications including steroids; (11) current and/or past regular use of non-steroid anti-inflammatory drugs; (12) current and/or past regular use of immune modifying drugs that target specific immune responses such as TNF antagonists; (13) current and/or past regular use of analgesics such as opioids; (14) current and/or past regular use of psychotropic medications, including antidepressants, anxiolytics, antipsychotics, hypnotics, sedatives, and barbiturates; (15) current and/or past regular use of cardiovascular medications, including antihypertensive, antiarrhythmic, antianginal, and anticoagulant drugs; (16) current smoking or excessive caffeine use (>600 mg/day) because of the known effects on proinflammatory cytokine levels; (17) evidence of recreational drug use from urine test. Health Factors: (18) BMI > 35 because of the effects of obesity on proinflammatory cytokine activity and also on risk for sleep disordered breathing; or (19) any abnormalities on screening laboratory tests.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Factorial Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: PO leucine & IV LPS
Oral (PO) leucine 6 g twice a day for 2 weeks followed by a single intravenous (IV) bolus of lipopolysaccharide (LPS) 0.8 ng/kg of body weight
|
amino acid leucine in powder
purified bacterial wall component as an inflammatory challenge
|
Experimental: PO placebo & IV LPS
PO maltodextrin (placebo) twice a day for 2 weeks followed by a single IV bolus of LPS 0.8 ng/kg of body weight
|
purified bacterial wall component as an inflammatory challenge
maltodextrin
|
Experimental: PO leucine & IV placebo
PO leucine 6 g twice a day for 2 weeks followed by a single IV bolus of 0.9% saline
|
amino acid leucine in powder
0.9% saline
|
Placebo Comparator: PO placebo & IV placebo
PO maltodextrin (placebo) twice a day for 2 weeks followed by a single IV bolus of 0.9% saline
|
maltodextrin
0.9% saline
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Depressed Mood From Baseline
Time Frame: At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration
|
Depression Subscale of the Short Form of the Profile of Mood States (POMS-SF): total score ranges from 0 to 32; higher values represent worse outcome, i.e., more severe depressed mood; the absolute values at each time point are presented here rather than change of values between time points; zero (0) in mean and standard deviation reflect measured data and not placeholder values.
|
At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Depressive Symptoms From Baseline
Time Frame: At baseline and then at 2 and 4 hours after LPS (or saline) administration
|
Montgomery-Asberg Depression Rating Scale (MADRS): a clinician-rated questionnaire of depressive symptoms with scores ranging from 0 to 60, with higher scores indicating more severe depressive symptoms.
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At baseline and then at 2 and 4 hours after LPS (or saline) administration
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Change in Feelings of Social Disconnection From Baseline
Time Frame: At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration
|
Feelings of Social Disconnection Scale: a self-report questionnaire of feelings of social disconnection with scores ranging from 0 to 28, with higher scores indicating more severe feelings of social disconnection.
|
At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration
|
Change in Fatigue From Baseline
Time Frame: At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration
|
Fatigue Subscale of the Short Form of the Profile of Mood States (POMS-SF): total score ranges from 0 to 20; higher values represent worse outcome, i.e., more severe fatigue; the absolute values at each time point are presented here rather than change of values between time points.
|
At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration
|
Change in Confusion From Baseline
Time Frame: At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration
|
Confusion Subscale of the Short Form of the Profile of Mood States (POMS-SF): total score ranges from 0 to 20; higher values represent worse outcome, i.e., more severe confusion; the absolute values at each time point are presented here rather than change of values between time points; zero (0) in mean and standard deviation reflect measured data and not placeholder values.
|
At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration
|
Change in Memory Domains of Cognitive Function From Baseline
Time Frame: At baseline and then 3 hours after LPS (or saline) administration
|
Memory domains of cognitive function were measured using the computerized tests from CNS Vital Signs™: verbal memory using "Verbal Memory Test" (total scores ranging from 0 to 60; higher scores mean a better outcome); and visual memory using "Visual Memory Test" (total scores ranging from 0 to 60; higher scores mean a better outcome).
The absolute values at each time point are presented.
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At baseline and then 3 hours after LPS (or saline) administration
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Change in Non-memory Domains of Cognitive Function From Baseline
Time Frame: At baseline and then 3 hours after LPS (or saline) administration
|
Non-memory domains of cognitive function were measured using the computerized tests from CNS Vital Signs™: executive function using "Stroop Test" (average reaction time in milliseconds thus ranging from 0 to infinite; shorter reaction time means a better outcome); and attention using "Shifting Attention Test" (average reaction time for correct responses in milliseconds thus ranging from 0 to infinite; shorter reaction time means a better outcome) and "Continuous Performance Test" (average reaction time for correct responses in milliseconds thus ranging from 0 to infinite; shorter reaction time means a better outcome).
The absolute values at each time point are presented.
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At baseline and then 3 hours after LPS (or saline) administration
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Anhedonia
Time Frame: 2 hours after LPS (or saline) administration
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Facial expressions and skin conductance in response to funny film clips using the iMotions®Attention Tool (iMotions Inc., Cambridge, MA) which performs automatic analysis of facial expressions from video and integrates simultaneous measurement of skin conductance
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2 hours after LPS (or saline) administration
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Subjective Sensitivity to Social Rejection
Time Frame: 2 hours after LPS (or saline) administration
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Using the Cyberball Social Exclusion Task, feelings of social distress to social rejection are evaluated based on a scale with the total score ranging from 0 to 48; higher values represent worse outcome, i.e., more severe social distress.
The Overall Number of Participants Analyzed is different from numbers of participants reported in the Participant Flow module because some participants declined to complete this task.
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2 hours after LPS (or saline) administration
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Negative Bias in Facial Emotion Recognition
Time Frame: 2 hours after LPS (or saline) administration
|
Emotional Face Recognition Task consists in showing participants a series of black and white photographs (Ekman Pictures of facial affect), in which the facial expression is morphed from neutral to either Sad, Angry, or Happy.
For each image, participants will be asked to make a forced choice about the emotion expressed, and rate their certainty.
|
2 hours after LPS (or saline) administration
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Subjective Sensitivity to Social Acceptance
Time Frame: 2 hours after drug administration
|
Prior to the experimental session, participants are asked to complete a survey that contains several personality questionnaires and are video-recorded for 2-5 minutes as they discuss what they like about themselves.
Participants are told that 8 people will form impressions of them by selecting personality traits to describe them.
Participants then see a photograph of themselves along with a descriptive word underneath (supposedly provided by the evaluators), which is pre-rated based on desirability, and are asked to rate subjective happiness when each of the feedback items is presented.
The total score of the scale ranges from 0 to 105; higher values represent better outcome, i.e., higher social reward.
The Overall Number of Participants Analyzed is different from numbers of participants reported in the Participant Flow module because some participants declined to complete this task.
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2 hours after drug administration
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Reward
Time Frame: 2 hours after LPS (or saline) administration
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Reward Learning Task (a laboratory based probabilistic reward task that objectively measures participants' ability to modulate behavior as a function of reward)
|
2 hours after LPS (or saline) administration
|
Change in Proinflammatory Cytokines From Baseline
Time Frame: At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration
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Plasma proinflammatory cytokines (interleukin-1 receptor antagonist, interleukin-6, tumor necrosis factor-α, and soluble tumor necrosis factor receptor)
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At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration
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Change in Kynurenine Metabolites From Baseline
Time Frame: At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration
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Plasma tryptophan, kynurenine, quinolinic acid, and kynurenic acid
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At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration
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Change in Gene Expression From Baseline
Time Frame: At baseline and 30 minutes after LPS (or saline) administration
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Genome-wide transcriptional profiling conducted using Illumina HT-12 BeadArrays
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At baseline and 30 minutes after LPS (or saline) administration
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Joshua H Cho, MD, PhD, University of California Los Angeles David Geffen School of Medicine
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- R21MH113915 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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