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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests an anti-inflammatory drug called infliximab to determine its effect on negative symptoms of schizophrenia, such as lack of motivation, which standard treatments often fail to improve. Researchers aim to understand if reducing inflammation can affect brain areas associated with motivation and reward. Participants will receive either infliximab or a placebo (an inactive substance) to compare effects. This study targets individuals diagnosed with schizophrenia or schizoaffective disorder who experience significant motivational deficits and have high levels of a blood marker indicating inflammation. As a Phase 4 trial, this research explores how an already FDA-approved treatment can benefit more patients.

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.

What is the safety track record for these treatments?

Research has shown that infliximab, already used for conditions like arthritis, is generally considered safe. Studies indicate that less than 1% of patients experienced a severe allergic reaction during their first dose. However, some evidence suggests that infliximab might increase the risk of mental health issues such as depression or anxiety. Specifically, individuals taking it for other diseases had a higher chance of experiencing these issues compared to those not taking it. Overall, most patients usually tolerate infliximab well, but awareness of these possible side effects is important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for schizophrenia, like antipsychotics, work by balancing neurotransmitters in the brain. But infliximab, an antibody typically used for autoimmune conditions, offers a fresh approach by targeting inflammation. Researchers are excited about infliximab because it works in a completely different way than current medications, potentially addressing inflammation that might play a role in schizophrenia. This novel mechanism could offer new hope for patients who don't fully respond to existing treatments.

What evidence suggests that infliximab might be an effective treatment for schizophrenia?

This trial will compare the effects of infliximab with a placebo in treating schizophrenia. Studies have shown that infliximab, a medication that reduces inflammation, might help treat certain mental health issues. It has been effective for people with high inflammation levels, which could be important for treating difficult symptoms of schizophrenia, such as lack of motivation. These symptoms are hard to manage with current medications. Research also shows that infliximab is generally safe and works well, similar to its original form, Remicade. By reducing inflammation, infliximab could help improve symptoms that don't respond to regular antipsychotic treatments. ^{1 6 7 8 9}

Who Is on the Research Team?

David R Goldsmith, MD

Principal Investigator

Assistant Professor

Are You a Good Fit for This Trial?

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

Significant motivational deficit as reflected by a score >17 on the Motivation and Pleasure Domain of the Brief Negative Symptom Scale. For patients with 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

Willing and able to give written informed consent

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7188945/

Psychiatric Adverse Events Associated With Infliximab

The present retrospective, observational study confirmed that IFX treatment is associated with an elevated risk of psychiatric adverse events.

2.

sciencedirect.com

sciencedirect.com/science/article/pii/S2666354622001089

Anti-inflammatory medications for the treatment of mental ...

This scoping review assessed the effect of anti-inflammatory medications in mental disorders. A search in Medline and the Cochrane database focusing on ...

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10754394/

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This study found that infliximab biosimilar products appear to be safe and effective, similar to their originator counterparts.

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researchgate.net

researchgate.net/publication/392870963_Neuroinflamation_Treatment_Options_in_Resistant_Schizophrenia-State_of_the_Art

(PDF) Neuroinflamation Treatment Options in Resistant ...

Infliximab showed efficacy primarily in patients with elevated inflammatory markers. Pentoxifylline showed anti-inflammatory properties and neuroprotective ...

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avsola.com

avsola.com/hcp/totality-of-evidence

AVSOLA®(infliximab-axxq)'s Totality of Evidence

AVSOLA is highly similar to Remicade based on a totality of evidence, with no clinically meaningful differences in safety and efficacy.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6977711/

Incidence of Adverse Psychiatric Events During Treatment of ...

The primary outcome was the reporting of APE (depression, anxiety, suicide or suicidal ideation, or psychosis) during treatment with infliximab, adalimumab, ...

7.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0003496724193260

Infliximab maintains a high degree of clinical response in ...

At week 54, major clinical response was achieved by 12.1% of patients in the infliximab group. The safety profile of infliximab through week 54 was consistent ...

8.

ctv.veeva.com

ctv.veeva.com/study/anti-inflammatory-challenge-in-schizophrenia

Anti-Inflammatory Challenge in Schizophrenia

This research project will explore negative symptoms of schizophrenia, such as motivational deficits, by examining the relationship between ...

9.

ajmc.com

ajmc.com/view/va-study-patients-switching-to-biosimilar-infliximab-more-likely-to-stop-treatment

VA Study: Patients Switching to Biosimilar Infliximab More ...

Those who switched from the infliximab reference product, Remicade, to an infliximab biosimilar were almost 3 times more likely to stop treatment.