Neural Response to Inflammatory Challenge in Major Depressive Disorder

Recruiting now · Phase 1/Phase 2 · Has a placebo group

Conditions studied: Major Depressive Disorder

In brief

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.

Key facts

Study ID

NCT04751331

Run by

Laureate Institute for Brain Research, Inc.

People needed

180

Starts

2021-05-15

Expected to finish

2026-12-01

Last updated by the study team

2026-04-21

Who can join

Age: 18 and older, up to 65. Sex: any. Healthy volunteers: accepted.

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…

• General Exclusion Criteria:
• Pregnancy
• A history of fainting during blood draws will be evaluated by the clinical team and may be deemed exclusionary.
• 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.
• Claustrophobia that is severe enough to preclude MRI scanning.
• Medications:
• Current and/or past regular use of hormone-containing medications (excluding contraceptives)
• Use of medications such as oral corticosteroids which may have immunosuppressive effects.
• Current use of non-steroid anti-inflammatory drugs that is deemed by the investigators to potentially confound the results of the study (e.g. > 3 days/week)
• Current and/or past regular use of immune modifying drugs that target specific immune responses such as TNF antagonists
• Current use of analgesics such as opioids or history of addiction to opioids or other analgesics
• Current and/or past regular use of cardiovascular medications, including antihypertensive, antiarrhythmic, anti-anginal, and anticoagulant drugs (does not apply where medications are taken for different purpose e.g. anti-hypertensives for migraine).

Where it is running

• Laureate Institute for Brain Research — Tulsa, Oklahoma, United States (enrolling)

Full record on ClinicalTrials.gov

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