Cognitive Dysfunction and Inflammation in Depression: Experimental Inhibition Via Infliximab

NCT06136546 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2023p002988
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a mechanistic randomized controlled trial that investigates whether inhibition of tumor necrosis factor signaling via intravenous infusion of infliximab improves psychomotor speed and executive functioning in depressed individuals who exhibit an inflammatory phenotype.

Conditions

Depressive Disorder, Major; Inflammation

Keywords

Depression; Major Depressive Disorder; Infliximab; Cognitive Dysfunction

Outcome Measures

Primary Outcomes (2)

• Psychomotor Speed (TestMyBrain: Simple Reaction Time)

  Faster within-person psychomotor speed (i.e. median response time)

  Repeated measures over two weeks

• Executive Function (TestMyBrain: Choice Reaction Time)

  Better within-person executive function performance (i.e. accuracy-adjusted response speed)

  Repeated measures over two weeks

Secondary Outcomes (3)

• Hamilton Depression Rating Scale (17-item; range 0-54)

  Week 2

• Dimensional Anhedonia Rating Scale (17-item; range 0-68)

  Week 2

• Concentrations of circulating C reactive protein

  Week 1

Study Arms (2)

Infliximab

EXPERIMENTAL

Participants in this arm will receive 5 mg/kg of infliximab via an in-dwelling catheter.

Drug: Infliximab

Placebo

PLACEBO COMPARATOR

Participants in this arm will receive saline as placebo via an in-dwelling catheter.

Other: Placebo

Interventions

Infliximab DRUG

Intravenous infusion of infliximab

Infliximab

Placebo OTHER

Intravenous infusion of saline solution (matching in color and consistency in infliximab)

Placebo

Eligibility Criteria

• Age: 25 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Aged 25-50 years
• Able to read and understand English and willing to provide informed consent/comply with the study protocol
• Willingness to complete intravenous infusion and have blood drawn
• Exhibit circulating blood level of C reactive protein ≥ 3mg/L
• Diagnosed with Major Depressive Disorder
• Moderate depressive symptom severity, as indicated by score ≥15 on the Hamilton Depression Rating Scale
• Antidepressant treatment free for at least 4 weeks prior to study entry or be on a fixed treatment regimen for at least 4 weeks; willingness to continue treatment status (i.e., change/begin new treatment) until study termination
• Willingness not to begin/change therapies until study termination (maximum of three weeks following screening)
• Be of non-childbearing potential per the following specific criteria:
• a. Non-childbearing potential (e.g., physiologically incapable of becoming pregnant, i.e., permanently sterilized (status post hysterectomy, bilateral tubal ligation), or is post-menopausal with her last menses at least one year prior to screening); or b. Childbearing potential and meets the following criteria: i. A negative serum pregnancy test within thirty days of infusion (may be repeated closer to infusion date at the discretion of the PI or study staff) and abstinent after the negative serum pregnancy test and prior to infusion; or ii. Using any form of hormonal birth control, on hormone replacement therapy started prior to 12 months of amenorrhea, using an intrauterine device (IUD), having a monogamous relationship with a partner who has had a vasectomy, or is sexually abstinent; iii. Continuously use one of the following methods of birth control over the last six months: implants, injectable or patch hormonal contraception, oral contraceptives, IUD, double-barrier contraception, sexual abstinence.

You may not qualify if:

• i. acute injury/infection within one week of study initiation or infection within one month of study initiation that required antibiotic/antiviral treatment ii. chronic infection (e.g., hepatitis B or C or HIV) or history of Covid 19 infection within the past 6 months or with persisting symptoms.
• iii. latent infection (e.g., tuberculosis, fungal infections), or history of recurrent infections, iv. uncontrolled cardiovascular, endocrine, hematologic, hepatic, renal or neurologic disease (as determined by medical history, physical exam and laboratory testing) v. cancer history vi. autoimmune conditions; neurologic conditions (controlled) that are known to substantially impact cognitive function (e.g., stroke).
• Of note, stable medical conditions such as diabetes and cardiovascular disease, will be allowed in the study as they can contribute to endogenous inflammation.
• Active antipsychotic and anticonvulsant medication use (that interact with infliximab)
• Prior use of a TNF antagonist or use of systemic corticosteroids or anti-proliferative agents within one year of study entry
• History of liver abnormalities
• Major cognitive impairment as determined by study investigators
• Active restrictive eating disorder or obsessive compulsive disorder deemed by study investigators to be primary cause of depressive disorder
• History of a psychotic disorder or Bipolar disorder type I/II
• Current substance use disorder (i.e., present in last six months), of greater than mild severity
• Suicidal ideation based on a score ≥3 on the Columbia-Suicide Severity Rating Scale
• Electroconvulsive therapy (ECT)/deep brain stimulation (DBS) within the last year, or report of persistent negative cognitive effects of ECT/DBS
• Presence of a transplanted solid organ
• Medication use affecting immune or cognitive function:
• i. Chronic use (\>1 month) of a benzodiazepine more than the equivalent of 2 mg of lorazepam ii. Use of anti-inflammatory agents during the study: non-steroidal anti-inflammatory agents (NSAIDs) (excluding 81mg of aspirin), glucocorticoid containing medicines or statins, or cyclooxygenase-2 (COX-2) inhibitors

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major; Inflammation; Depression; Cognitive Dysfunction

Interventions

Infliximab

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavioral Symptoms; Behavior; Cognition Disorders; Neurocognitive Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Naoise Mac Giollabhui, PhD

CONTACT

6177241000; nmacgiollabhui@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All treatment teams, outcome assessors, and data analysts will be blind to randomization assignment until the primary study results have been analyzed.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Member of the Faculty

Model Details: A permuted block design (n=4) on a 1:1 allocation will be used to assign participants to each intervention group.

Study Record Dates

• First Submitted: November 13, 2023
• First Posted: November 18, 2023
• Study Start: January 23, 2025
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): January 31, 2029
• Last Updated: May 7, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)