Leucine for Depression Study (L-DEP)

NCT03557684 | Terminated Early Phase 1 Results DMC FDA Drug

• 1 other identifier: R21MH113915
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

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.

Conditions

Depression

Outcome Measures

Primary Outcomes (1)

• Change in Depressed Mood From Baseline

  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 Outcomes (6)

• Change in Depressive Symptoms From Baseline

  At baseline and then at 2 and 4 hours after LPS (or saline) administration

• Change in Feelings of Social Disconnection From Baseline

  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

  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

  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

  At baseline and then 3 hours after LPS (or saline) administration

Other Outcomes (8)

• Anhedonia

  2 hours after LPS (or saline) administration

• Subjective Sensitivity to Social Rejection

  2 hours after LPS (or saline) administration

• Negative Bias in Facial Emotion Recognition

  2 hours after LPS (or saline) administration

Study Arms (4)

PO leucine & IV LPS

EXPERIMENTAL

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; Biological: lipopolysaccharide (LPS)

PO placebo & IV LPS

EXPERIMENTAL

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; Biological: lipopolysaccharide (LPS)

PO leucine & IV placebo

EXPERIMENTAL

PO leucine 6 g twice a day for 2 weeks followed by a single IV bolus of 0.9% saline

Dietary Supplement: leucine; Other: IV placebo

PO placebo & IV placebo

PLACEBO COMPARATOR

PO maltodextrin (placebo) twice a day for 2 weeks followed by a single IV bolus of 0.9% saline

Other: PO placebo; Other: IV placebo

Interventions

leucine DIETARY_SUPPLEMENT

amino acid leucine in powder

PO leucine & IV LPS; PO leucine & IV placebo

PO placebo OTHER

maltodextrin

PO placebo & IV LPS; PO placebo & IV placebo

lipopolysaccharide (LPS) BIOLOGICAL

purified bacterial wall component as an inflammatory challenge

PO leucine & IV LPS; PO placebo & IV LPS

IV placebo OTHER

0.9% saline

PO leucine & IV placebo; PO placebo & IV placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

Sponsors & Collaborators

• University of California, Los Angeles: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

UCLA Cousins Center for Psychoneuroimmunology

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Depression

Interventions

Leucine; Lipopolysaccharides

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential; Glycoconjugates; Carbohydrates; Polysaccharides, Bacterial; Polysaccharides; Lipids; Antigens, Bacterial; Antigens; Biological Factors; Endotoxins; Bacterial Toxins; Toxins, Biological

Results Point of Contact

• Title: Joshua H. Cho, MD, PhD
• Organization: UCLA

hjcho@mednet.ucla.edu

3104286218

Study Officials

• Joshua H Cho, MD, PhD

  University of California Los Angeles David Geffen School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 5, 2018
• First Posted: June 15, 2018
• Study Start: September 1, 2018
• Primary Completion: July 31, 2021
• Study Completion: July 31, 2021
• Last Updated: June 8, 2023
• Results First Posted: June 8, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)