Recruiting

Anti-Inflammatory

Sponsor:

Emory University

Code:

NCT05823532

Conditions

Schizophrenia

Eligibility Criteria

Sex: All

Age: 18 - 55

Healthy Volunteers: Not accepted

Interventions

Infliximab

Placebo

Study Details

Brief summary:

This study aims to illuminate the biological underpinnings of negative symptoms in schizophrenia-particularly motivational impairments-by probing the link between systemic inflammation and neural activity in reward-related brain circuits.

The primary goal of this study is to determine:

  • Ventral Striatum Activation: Assess how reward anticipation engages the ventral striatum in individuals with schizophrenia, both before and after an anti-inflammatory intervention.
  • Anterior Insula Activation: Examine how increasing effort demands modulate activity in the anterior insula under the same conditions.

Conditions

Schizophrenia

Study ID

NCT05823532

Start date

Apr 18, 2024

Status verified date

Jun, 2026

Completion date

Mar, 2028

Anticipated

Primary completion date

Mar, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 55

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Men or women, 18-55 years of age with a primary diagnosis of Diagnostic and Statistical Manual of Mental Disorders (DSM-V) schizophrenia or schizoaffective disorder;
  • Willing and able to give written informed consent;
  • Plasma CRP ≥2 mg/L;
  • Significant motivational deficit as reflected by a score >17 on the Motivation and Pleasure Domain of the Brief Negative Symptom Scale. Of note, for patients who exhibit CRP>10mg/L, additional CRP testing will be conducted at 2-week intervals as per American Heart Association/ Center for Disease and Control Prevention guidelines to establish stability and rule out acute inflammation/infection (along with physical exam and laboratory testing).
  • Patients must also have a negative urine drug screen at all study visits.

Exclusion Criteria:

  • Any autoimmune disorder (as confirmed by laboratory testing);
  • History of tuberculosis infection as determined by QuantiFERON Gold or high risk of tuberculosis exposure;
  • Active hepatitis B or C infection or human immunodeficiency virus infection (as established by laboratory testing);
  • History of any type of cancer;
  • History of fungal infection;
  • History of recurrent viral or bacterial infections;
  • Unstable cardiovascular (including evidence of congestive heart failure as determined by physical examination and laboratory testing), endocrinologic, hematologic, hepatic, renal, and neurological disease (as determined by physical examination and laboratory testing);
  • Demyelinating brain disease and/or a concerning structural abnormality seen on MRI;
  • Substance abuse/dependence within 6 months of study entry (as determined by MINI and urine drug screen);
  • Primary diagnosis of mood or anxiety disorder (i.e., major depressive disorder, bipolar disorder, post-traumatic stress disorder) as determined by the International Neuropsychiatric Interview for Schizophrenia and Psychotic Disorders (MINI).
  • Active suicidal ideation or plan;
  • An active eating disorder;
  • A history of cognitive disorder or Mini-Mental State Exam (MMSE) < 24 (indicating cognitive impairment);
  • Pregnancy or lactation;
  • Treatment with clozapine (given increased risk of neutropenia/agranulocytosis);
  • Women of childbearing potential who are not using a medically accepted means of contraception;
  • Known allergy to murine products or other biologic therapies;
  • Previous organ transplant;
  • Administration of any modified live virus vaccine within one month of study entry, during the study, and for at least one month after the final study visit;
  • Oral glucocorticoids, immunosuppressive drugs (e.g. anti-cytokine therapies or methotrexate), or any other drugs targeting the immune system within 6 months of baseline;
  • Chronic use of non-steroidal anti-inflammatory agents (NSAIDs; excluding 81mg of aspirin), glucocorticoid-containing medications, or minocycline or non-prescription supplements with known or suspected anti-inflammatory properties (e.g. fish oil supplements, curcumin, pre- or probiotics) within 2 weeks of baseline or at any time during the study;
  • Use of non-steroidal anti-inflammatory agents (NSAIDs), and glucocorticoid medications at any time during the study;
  • Any contraindication to MRI. Due to the high co-morbidity between schizophrenia and mood/anxiety disorders, the study team plans to include patients with these diagnoses as long as schizophrenia is the primary diagnosis.
  • Subjects may be taking psychotropic medications at the time of the study (including antipsychotics, antidepressants, mood stabilizers, and benzodiazepines) but may have no psychotropic medication changes for one month before study enrollment or during participation in the study. Patients with stable medical conditions and on medications for those conditions will not be excluded. No patient will be removed from antipsychotic treatment for this study.

Study Design

Enrollment

60 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

experimental: Infliximab

Subjects will be stratified by sex and randomized before this visit in preparation for the infusion. Vitals and safety labs will be drawn at this visit as well as urine testing for drugs of abuse and pregnancy testing for all biological females. Patients will receive breakfast followed by a double-blinded infusion of infliximab (5mg/kg body weight) in the GCSTA Clinical Research Center at Emory University Hospital. The infusion will last 2.5 hours, and subjects will be monitored during the infusion and for one hour after completion for the possible development of anaphylaxis, which occurs in less than 1% of patients receiving an initial dose of infliximab

placebo comparator: Placebo

Subjects will be stratified by sex and randomized prior to this visit in preparation for the infusion. Vitals and safety labs will be drawn at this visit as well as urine testing for drugs of abuse and pregnancy testing for all biological females. Patients will receive breakfast followed by a double-blinded infusion of saline in the GCSTA Clinical Research Center at Emory University Hospital. The infusion will last 2- 2.5 hours, and subjects will be monitored during the infusion and for one hour after completion for the possible development of anaphylaxis, which occurs in less than 1% of patients receiving an initial dose of infliximab

Interventions

Infliximab

Infliximab has FDA approval for the treatment of rheumatoid arthritis and inflammatory bowel syndrome. The current proposal represents the use of infliximab as an experimental tool to dissect the role of inflammatory processes leading to changes in brain reward circuitry and changes in specific symptom domains.

Double-blinded infusions of infliximab will be administered in the GCTSA Clinical Research Center, located at Emory University Hospital. Independent pharmacists will dispense either infliximab or placebo in a 250ml saline bag according to a computer-generated randomization list provided by the study pharmacist.

Placebo

Double-blinded infusions of saline will be administered in the GCTSA Clinical Research Center, located at Emory University Hospital. Independent pharmacists will dispense either infliximab or placebo in a 250ml saline bag according to a computer-generated randomization list provided by the study pharmacist.

Primary outcome measure

  • Changes in Monetary Incentive Delay Task (MID) [ Time Frame: Study visits: 1-3 days before intervention and 2 weeks post-intervention ] ]
  • Changes in Effort Based Decision Making Task (EBDM) [ Time Frame: 1-3 days before intervention, 2 weeks post intervention ]
  • Changes in C-Reactive Protein (CRP) [ Time Frame: Study Visits :1-3 days before intervention, 1 day post-intervention, 3 days, 1 week and 2 weeks post-intervention ]
  • Changes in Brief Negative Symptom Scale (BNSS) [ Time Frame: 1-3 days before intervention, 1 day, 3 days, 1 week, and 2 weeks post intervention ]
  • Changes in Performance on the Effort Expenditure for Reward Task (EEfRT) [ Time Frame: Study Visits :1-3 days before intervention and 2 weeks post intervention ]

Central Contacts and Locations

Central contacts

David R Goldsmith, MD

404-727-3735drgolds@emory.edu

Corinne Dotts

corinne.jeanne.dotts@emory.edu

Locations

Grady Memorial Hospital

Recruiting

Atlanta, Georgia, United States, 30303

Contacts

David R Goldsmith, MD

404-727-3735csning@emory.edu

Emory University Hospital

Recruiting

Atlanta, Georgia, United States, 30322

Contacts

David R Goldsmith, MD

404-727-3735csning@emory.edu

More Information

Sponsor

Emory University

Last update posted

Jun 3, 2026

Last verified

Jun, 2026

Keywords

  • Inflammation
  • Reward-related Brain Regions

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-26. This information was provided to ClinicalTrials.gov by Emory University on 2026-06-03. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.