Neural Response to Inflammatory Challenge in Major Depressive Disorder

NCT04751331 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 2020-004-00
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

This is a parallel group, double-blinded, placebo-controlled study. Participants with MDD (n=90) and HC (n=90) will be randomly assigned (2:1) to receive either lipopolysaccharide (LPS) (0.8ng/kg of body weight) or placebo (same volume of 0.9% saline) administered as an intravenous bolus. This will yield the following groups: MDD-LPS (n=60), MDD-Placebo (n=30), HC-LPS (n=60), HC-placebo (n=30). There are three main aims: to identify immune pathways and neural circuits that respond differently to LPS in MDD vs. HC subjects; (2) to test whether the strength of inflammatory changes induced by LPS is associated with degree of change in anhedonic symptoms and neural circuits in the MDD group, and (3) to identify a biotype of MDD that shows a differential immunological and neurophysiological response to LPS. The main outcome variables are symptoms of anhedonia measured with the Snaith-Hamilton Pleasure Scale (SHAPS), cytokines (Il-6, IL-8, IL-10, and TNF), and BOLD signal change in the neural circuitry mediating interoceptive processing, i.e. the insula and cingulate cortex. The exploratory aim is to determine whether the acute inflammatory response to LPS can predict the clinical course of depression over a period of six months. The main outcome of this component of the study is self-reported depressive symptoms assessed with the QIDS-SR.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• Inflammatory response

  Serum interleukin 6 (IL-6) (pg/mL)

  1.5 hours post infusion

Secondary Outcomes (4)

• Symptoms of anhedonia

  1.5 hours post infusion

• Depressive Symptoms

  24 hours post infusion

• Neural response to anticipation of monetary reward

  Two hours post-infusion

• Neural response to interoceptive vs exteroceptive stimuli (interoceptive awareness task)

  Two hours post infusion

Other Outcomes (3)

• Temperature

  3-5 hours post infusion

• Inflammatory response

  1.5 hours post-infusion

• Course of Illness

  6 months

Study Arms (2)

LPS

EXPERIMENTAL

Lipopolysaccharide (LPS) (0.8ng/kg of body weight; E. coli group O:113) administered as an intravenous bolus.

Biological: LPS

Placebo

PLACEBO COMPARATOR

Placebo (same volume of 0.9% saline) administered as an intravenous bolus

Biological: Saline

Interventions

LPS BIOLOGICAL

Lipopolysaccharide (LPS) (0.8ng/kg of body weight; E. coli group O:113)

LPS

Saline BIOLOGICAL

0.9% saline administered as an intravenous bolus

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:

• Both healthy controls and depressed participants will be required to be in good general health (as evaluated during Visit 1, including EKG) and to be 18-65 years of age. A DSM-V diagnosis of MDD will be made with the MINI International Neuropsychiatric Interview and current symptoms of depression will be measured with the clinician-administered MADRS and the self-report PHQ-9. Depressed participants will be required to have symptoms of depression (i.e. a PHQ-9 score ≥10) and/or a MADRS score of ≥7.

You may not qualify if:

• Pregnancy
• Medical Conditions:
• Moderate to severe traumatic brain injury (\>30 min. loss of consciousness or \>24 hours posttraumatic amnesia) or other neurocognitive disorder with evidence of neurological deficits.
• 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
• Contraindications for MRI:
• Cardiac pacemaker, metal fragments in eyes/skin/body (shrapnel), aortic/aneurysm clips, prosthesis, by-pass surgery/coronary artery clips, hearing aid, heart valve replacement, shunt (ventricular or spinal), electrodes, metal plates/pins/screws/wires, or neuro/bio-stimulators (TENS unit), persons who have ever been a professional metal worker/welder, history of eye surgery/eyes washed out because of metal, vision problems uncorrectable with lenses, inability to lie still on one's back for 60 minutes; prior neurosurgery; tattoos or cosmetic makeup with metal dyes, unwillingness to remove body piercings, and pregnancy.

Sponsors & Collaborators

• Laureate Institute for Brain Research, Inc.: lead

Study Sites (1)

Laureate Institute for Brain Research

Tulsa, Oklahoma, 74136, United States

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Central Study Contacts

Jonathan Savitz, PhD

CONTACT

918 502 5104; jsavitz@laureateinstitute.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2021
• First Posted: February 12, 2021
• Study Start: May 15, 2021
• Primary Completion: April 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)