Infliximab for Schizophrenia

Recruiting at 1 trial location

Overseen By Robin Gross

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Emory University

Must not be taking: Clozapine, Immunosuppressives, NSAIDs, others

Disqualifiers: Autoimmune disorders, Cancer, Substance abuse, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 9

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This research project will explore negative symptoms of schizophrenia, such as motivational deficits, by examining the relationship between inflammation and reward-related brain regions. To accomplish this, we will administer a single infusion of either the anti-inflammatory medication infliximab or placebo (n=10 per group) to patients with high inflammation. This study is important because schizophrenia can be a chronic and debilitating neuropsychiatric disorder and negative symptoms are some of the most difficult aspects of schizophrenia associated with worst functional outcomes. These symptoms do not typically respond to antipsychotic therapies, and as such, there are no current medications to treat negative symptoms.

Do I have to stop taking my current medications for the trial?

You can continue taking your current psychotropic medications (like antipsychotics, antidepressants, mood stabilizers, and benzodiazepines) as long as there are no changes for one month before and during the study. However, you must stop using certain anti-inflammatory medications and supplements two weeks before the study and during the study.

How does the drug Infliximab differ from other treatments for schizophrenia?

Infliximab is unique because it is an anti-inflammatory drug typically used for autoimmune disorders, and its use in schizophrenia is based on the idea that inflammation may play a role in the condition. Unlike traditional antipsychotic medications, Infliximab targets inflammation, which is a novel approach for treating schizophrenia. ^{1 2 3 4 5}

Research Team

David R Goldsmith, MD

Principal Investigator

Assistant Professor

Eligibility Criteria

This trial is for men and women aged 18-45 with schizophrenia or schizoaffective disorder, who have high inflammation levels and severe motivational deficits. Participants must not have any autoimmune disorders, active infections like TB or hepatitis, cancer history, unstable diseases, substance abuse within the last six months, or be on certain medications.

Inclusion Criteria

Patients must also have a negative urine drug screen at all study visits

Willing and able to give written informed consent

Plasma CRP 3mg/L

Exclusion Criteria

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)

Substance abuse/dependence within 6 months of study entry (as determined by MINI and urine drug screen)

Timeline

Pre-screening

Initial assessment including mood and negative symptoms of schizophrenia, blood sampling for CRP, urine drug screen, and pregnancy testing

1-2 hours

1 visit (in-person)

Screening

Participants are screened for eligibility to participate in the trial

1 visit

1 visit (in-person)

Baseline

Assessment of adverse events, behavioral assessments, blood sampling, fMRI scan, and randomization to study drug or placebo

5-6 hours

1 visit (in-person)

Infusion

Infusion of study drug or placebo, monitoring for adverse events, and safety assessments

5 hours

1 visit (in-person)

Post-Infusion Monitoring

Follow-up visits to assess adverse events, conduct behavioral assessments, and perform safety labs

2 weeks

4 visits (in-person)

Follow-up

One-month follow-up safety check-in via phone call to assess for adverse events

10-15 minutes

1 visit (virtual)

Treatment Details

Interventions

• Infliximab
• Placebo

Trial Overview The study tests if a single infusion of infliximab (an anti-inflammatory drug) can improve negative symptoms in schizophrenia patients with high inflammation compared to a placebo. There are two groups: one receiving infliximab and the other a placebo.

Participant Groups

Group I: Infliximab Experimental Treatment 1 Intervention

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 infliximab (5mg/kg body weight) in the GCSTA Clinical Research Center at Emory University Hospital. The infusion will last 3 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

Group II: Placebo Placebo Group 1 Intervention

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 3 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

Infliximab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Remicade for:

• Ankylosing Spondylitis
• Crohn's Disease
• Ulcerative Colitis
• Psoriatic Arthritis
• Rheumatoid Arthritis
• Plaque Psoriasis

Approved in United States as Remicade for:

• Ankylosing Spondylitis
• Crohn's Disease
• Ulcerative Colitis
• Psoriatic Arthritis
• Rheumatoid Arthritis
• Plaque Psoriasis

Approved in Canada as Remicade for:

• Ankylosing Spondylitis
• Crohn's Disease
• Ulcerative Colitis
• Psoriatic Arthritis
• Rheumatoid Arthritis
• Plaque Psoriasis

Approved in Japan as Remicade for:

• Ankylosing Spondylitis
• Crohn's Disease
• Ulcerative Colitis
• Psoriatic Arthritis
• Rheumatoid Arthritis
• Plaque Psoriasis

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Findings from Research

The TargetFlame trial is a multicenter, randomized, placebo-controlled study involving 109 patients with schizophrenia spectrum disorders who have an inflammatory profile, aiming to evaluate the efficacy and safety of adding 400 mg of Celecoxib to their ongoing antipsychotic treatment over 8 weeks.

This study is significant as it focuses on a specific subset of patients with an inflammatory profile, potentially leading to a more targeted and effective treatment approach for schizophrenia by repurposing Celecoxib as an anti-inflammatory augmentation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of add-on Celecoxib treatment on patients with schizophrenia spectrum disorders and inflammatory cytokine profile trial (TargetFlame): study design and methodology of a multicentre randomized, placebo-controlled trial. Strube, W., Aksar, A., Bauer, I., et al.[2023]

In a randomized clinical trial with 40 patients, adalimumab, when added to risperidone, significantly reduced negative and general psychopathology symptoms of chronic schizophrenia compared to a placebo, as measured by the PANSS scale.

The study found no significant side effects associated with adalimumab treatment, indicating it may be a safe adjunctive therapy for managing certain symptoms of schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risperidone combination therapy with adalimumab for treatment of chronic schizophrenia: a randomized, double-blind, placebo-controlled clinical trial. Motamed, M., Karimi, H., Sanjari Moghaddam, H., et al.[2023]

A new study is investigating the effects of low-dose methotrexate, an anti-inflammatory drug, on schizophrenia symptoms in 72 patients over 3 months, aiming to see if it can improve both positive and negative symptoms as well as cognitive functioning.

Previous research suggests that inflammation plays a role in schizophrenia, and this study builds on evidence that anti-inflammatory treatments, like methotrexate, may provide benefits when added to standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised double-blind placebo-controlled 12- week feasibility trial of methotrexate added to treatment as usual in early schizophrenia: study protocol for a randomised controlled trial. Chaudhry, IB., Husain, N., ur Rahman, R., et al.[2021]

Infliximab, an anti-inflammatory drug used for autoimmune disorders, can lead to severe psychiatric side effects, including depression and suicidal behaviors, particularly in adolescents, as demonstrated in a case involving a 16-year-old male with Crohn's disease.

This case highlights the importance of screening for preexisting psychiatric conditions in young patients before starting infliximab, as the patient developed significant depressive symptoms shortly after treatment initiation, but successfully managed these symptoms with fluoxetine and psychotherapy without recurrence during subsequent infusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infliximab-induced Depression and Suicidal Behavior in Adolescent with Crohn's Disease: Case Report and Review of Literature. Shayowitz, M., Bressler, M., Ricardo, AP., et al.[2022]

A systematic review of 56 randomized controlled trials found that certain anti-inflammatory agents, specifically aspirin, estrogens, minocycline, and N-acetylcysteine (NAC), significantly reduced symptoms of schizophrenia, particularly in early-phase patients.

The study highlighted that while some agents showed promise, others like bexarotene and celecoxib did not demonstrate significant effects, indicating that not all anti-inflammatory treatments are effective for schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the efficacy of anti-inflammatory agents for patients with schizophrenia: a meta-analysis. Çakici, N., van Beveren, NJM., Judge-Hundal, G., et al.[2020]

References

1. Austria pubmed.ncbi.nlm.nih.gov

Effects of add-on Celecoxib treatment on patients with schizophrenia spectrum disorders and inflammatory cytokine profile trial (TargetFlame): study design and methodology of a multicentre randomized, placebo-controlled trial. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Risperidone combination therapy with adalimumab for treatment of chronic schizophrenia: a randomized, double-blind, placebo-controlled clinical trial. [2023]

3. England pubmed.ncbi.nlm.nih.gov

A randomised double-blind placebo-controlled 12- week feasibility trial of methotrexate added to treatment as usual in early schizophrenia: study protocol for a randomised controlled trial. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Infliximab-induced Depression and Suicidal Behavior in Adolescent with Crohn's Disease: Case Report and Review of Literature. [2022]

5. England pubmed.ncbi.nlm.nih.gov

An update on the efficacy of anti-inflammatory agents for patients with schizophrenia: a meta-analysis. [2020]