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Trial record 2 of 11 for:    lipopolysaccharide AND depression

Leucine for Depression Study (L-DEP)

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ClinicalTrials.gov Identifier: NCT03557684
Recruitment Status : Recruiting
First Posted : June 15, 2018
Last Update Posted : October 16, 2018
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Hyong Jin Cho, University of California, Los Angeles

Brief Summary:
Depression is very common and poses a huge disease burden. About 20% of the US population suffers from depression at lease once in their lifetime. Inflammations that are hidden inside our body as a result of aging, obesity, chronic diseases, or certain treatments (e.g., interferon for hepatitis C) appear to cause depressive symptoms and even clinical depression. Individuals with such inflammations are more likely to suffer from depression and are less likely to respond to currently available antidepressant medications. This study will test leucine, an amino acid, as a new way to mitigate depressive symptoms in response to such inflammations. This study begins with a 90-minute screening session to determine whether participants are eligible to join the main study. Those who meet the eligibility criteria will then join the main study, which will consist of taking leucine or maltodextrin (i.e., oral placebo) for 2 weeks at home and an 8-hour session at the UCLA Medical Center. A brief telephone follow-up every 3 months for 2 years with questions on mood is also planned. Approximately 90 healthy adults will be recruited for participation in the study. During the course of the study, participants will take leucine or maltodextrin for 2 weeks at home and then will be injected either lipopolysaccharide (LPS) or saline (i.e., intravenous placebo) at the UCLA Medical Center. LPS is a bacterial substance that can initiate chemical reactions that are similar to those seen in individuals with mild sickness symptoms, such as a slight increase in body temperature, muscle aches, or tiredness. It is a safe way of investigating the body's response to inflammation and how these changes may alter cognitive, emotional, or neural function. It has been given thousands of times to healthy volunteers - both younger and older adults - without any serious side effects.

Condition or disease Intervention/treatment Phase
Depression Dietary Supplement: leucine Other: PO placebo Biological: lipopolysaccharide (LPS) Other: IV placebo Early Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: An Experimental Treatment Approach for Inflammation-Induced Depression
Actual Study Start Date : September 1, 2018
Estimated Primary Completion Date : July 31, 2020
Estimated Study Completion Date : July 31, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Leucine

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
Dietary Supplement: leucine
amino acid leucine in powder

Biological: lipopolysaccharide (LPS)
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
Other: PO placebo
maltodextrin

Biological: lipopolysaccharide (LPS)
purified bacterial wall component as an inflammatory challenge

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
Dietary Supplement: leucine
amino acid leucine in powder

Other: IV placebo
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
Other: PO placebo
maltodextrin

Other: IV placebo
0.9% saline




Primary Outcome Measures :
  1. 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 ]
    Short Form of the Profile of Mood States (POMS-SF)


Secondary Outcome Measures :
  1. Change in depressive symptoms from baseline [ Time Frame: At baseline and then at 2, 4, and 6 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.

  2. 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.

  3. 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 ]
    Short Form of the Profile of Mood States (POMS-SF)

  4. 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 ]
    Profile of Mood States (POMS) Confusion subscale

  5. Change in cognitive function from baseline [ Time Frame: At baseline and then 3 hours after LPS (or saline) administration ]
    Verbal memory, visual memory, executive function, and attention measured using computerized tests from CNS Vital Signs™ including Verbal Memory Test, Visual Memory Test, Stroop Test, Shifting Attention Test, and Continuous Performance Test


Other Outcome Measures:
  1. Anhedonia [ Time Frame: 2 hours after LPS (or saline) administration ]
    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

  2. Subjective Sensitivity to Social Rejection [ Time Frame: 2 hours after LPS (or saline) administration ]
    Cyberball Social Exclusion Task

  3. Negative Bias in Facial Emotion Recognition [ Time Frame: 2 hours after LPS (or saline) administration ]
    Emotional Face Recognition Task

  4. Subjective Sensitivity to Social Acceptance [ Time Frame: 2 hours after drug administration ]
    Positive Social Feedback Task

  5. Reward [ Time Frame: 2 hours after LPS (or saline) administration ]
    Reward Learning Task

  6. 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 ]
    Plasma proinflammatory cytokines (interleukin-1 receptor antagonist, interleukin-6, tumor necrosis factor-α, and soluble tumor necrosis factor receptor)

  7. 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 ]
    Plasma tryptophan, kynurenine, quinolinic acid, and kynurenic acid

  8. Change in gene expression from baseline [ Time Frame: At baseline and 30 minutes after LPS (or saline) administration ]
    Genome-wide transcriptional profiling



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03557684


Contacts
Contact: Gracie Pineda 310-825-8425 grpineda@g.ucla.edu

Locations
United States, California
UCLA Cousins Center for Psychoneuroimmunology Recruiting
Los Angeles, California, United States, 90095
Contact: Gracie Pineda    310-825-8425    grpineda@g.ucla.edu   
Principal Investigator: Joshua H Cho, MD, PhD         
Sponsors and Collaborators
University of California, Los Angeles
National Institute of Mental Health (NIMH)
Investigators
Principal Investigator: Joshua H Cho, MD, PhD University of California Los Angeles David Geffen School of Medicine

Responsible Party: Hyong Jin Cho, Principal Investigator, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT03557684     History of Changes
Other Study ID Numbers: R21MH113915 ( U.S. NIH Grant/Contract )
R21MH113915 ( U.S. NIH Grant/Contract )
First Posted: June 15, 2018    Key Record Dates
Last Update Posted: October 16, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Depression
Depressive Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders