Lipopolysaccharide (LPS) Challenge in Depression

NCT03142919 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 2016-002-00
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

LPS Challenge in Individuals with Major Depressive Disorder

Conditions

Major Depressive Disorder

Keywords

Mood Disorder; MDD; Endotoxin; MRI; CRP

Outcome Measures

Primary Outcomes (1)

• Change in Snaith-Hamilton Pleasure Scale (SHAPS)

  The SHAPS is a 14-item self-administered questionnaire, with each item scored from 1-4 (strongly agree through strongly disagree; range 14-56), with higher scores indicating greater anticipatory, not consummatory, anhedonia. Disagreement (i.e. score of 3 or 4) on at least three items is defined as indicating clinically significant anhedonia.

  2-hours

Secondary Outcomes (7)

• Change in Montgomery-Asberg Depression Rating Scale (MADRS)

  24 hours

• Change in Interleukin 6 (IL-6) Protein Levels

  2-hours

• Change in Interleukin 10 (IL-10) Protein Levels

  2-hours

• Change in Tumor Necrosis Factor (TNF) Protein Levels

  2-hours

• Percent Signal Change in Blood Oxygenation Level Dependent Signal (BOLD) of the Ventral Striatum Reward Versus No Reward Condition

  Baseline line; 2-3 hours

Study Arms (4)

High CRP LPS Intervention

EXPERIMENTAL

High CRP Individuals with Major Depressive Disorder receiving LPS intervention

Biological: Lipopolysaccharide

Low CRP LPS Intervention

ACTIVE COMPARATOR

Low CRP Individuals with Major Depressive Disorder receiving LPS intervention

Biological: Lipopolysaccharide

High CRP LPS Placebo

PLACEBO COMPARATOR

High CRP Individuals with Major Depressive Disorder receiving placebo

Biological: Placebo

Low CRP LPS Placebo

PLACEBO COMPARATOR

Low CRP Individuals with Major Depressive Disorder receiving placebo

Biological: Placebo

Interventions

Lipopolysaccharide BIOLOGICAL

Lipopolysaccharide (LPS) derived from E. Coli group O 113:H10:K negative

Also known as: Endotoxin, CCRE

High CRP LPS Intervention; Low CRP LPS Intervention

Placebo BIOLOGICAL

Saline solution

Also known as: Saline solution

High CRP LPS Placebo; Low CRP LPS Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Depressed participants will be required to be in good general health (as evaluated during Visit 1, including EKG) and to be 18-55 years of age. Depressed participants will be required to have symptoms of depression (i.e. a PHQ-9 score ≥10) and be unmedicated for at least 3 weeks (8 weeks for fluoxetine) or treated with only one anti-depressant medication. Half the depressed participants (N=50) will be required to have a high-sensitivity C-Reactive Protein (CRP) score of ≥3 mg/L, and half the participants will be required to have a CRP score of ≤1 mg/L.

You may not qualify if:

• Pregnancy
• Previous history of fainting during blood draws.
• Medical Conditions:
• A history of a head injury with loss of consciousness.
• Presence of co-morbid medical conditions not limited to but including cardiovascular (e.g., history of acute coronary event, stroke) and neurological diseases (e.g., Parkinson's disease), as well as pain disorders.
• Presence of co-morbid inflammatory disorders such as rheumatoid arthritis or other autoimmune disorders.
• 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.
• Presence of chronic infection that may elevate pro-inflammatory cytokines.
• Presence of an acute infectious illness or receipt of a vaccination in the two weeks prior to an experimental session.
• Psychiatric Disorders:
• Current severe suicidal ideation or attempt within the past 12 months.
• Psychosis
• Bipolar disorder
• Substance abuse or dependence within the previous 6 months
• Age of onset of depression \>40 years

Sponsors & Collaborators

• Laureate Institute for Brain Research, Inc.: lead

Study Sites (1)

Laureate Institute for Brain Research

Tulsa, Oklahoma, 74136, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Mood Disorders

Interventions

Lipopolysaccharides; Endotoxins; Saline Solution

Condition Hierarchy (Ancestors)

Depressive Disorder; Mental Disorders

Intervention Hierarchy (Ancestors)

Glycoconjugates; Carbohydrates; Polysaccharides, Bacterial; Polysaccharides; Lipids; Antigens, Bacterial; Antigens; Biological Factors; Bacterial Toxins; Toxins, Biological; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Jonathan Savitz
• Organization: LIBR

jsavitz@laureateinstitute.org

9185025104

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: April 28, 2017
• First Posted: May 8, 2017
• Study Start: September 7, 2017
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: July 2, 2025
• Results First Posted: July 2, 2025

Record last verified: 2025-06

Locations

US (1)