Infliximab for Schizophrenia
Recruiting in Palo Alto (17 mi)
+1 other location
Overseen ByDavid R Goldsmith, MD
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: Emory University
Must not be taking: Clozapine, Immunosuppressives, NSAIDs, others
Disqualifiers: Autoimmune disorders, Cancer, Substance abuse, others
Prior Safety Data
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.
12345Eligibility 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
+2 more
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)
+21 more
Trial 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)
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: InfliximabExperimental Treatment1 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: PlaceboPlacebo Group1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Grady Memorial HospitalAtlanta, GA
Emory University HospitalAtlanta, GA
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Who Is Running the Clinical Trial?
Emory UniversityLead Sponsor
National Institute of Mental Health (NIMH)Collaborator
References
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]Neuroinflammation has been proposed to impact symptomatology in patients with schizophrenia spectrum disorders. While previous studies have shown equivocal effects of treatments with add-on anti-inflammatory drugs such as Aspirin, N-acetylcysteine and Celecoxib, none have used a subset of prospectively recruited patients exhibiting an inflammatory profile. The aim of the study is to evaluate the efficacy and safety as well as the cost-effectiveness of a treatment with 400 mg Celecoxib added to an ongoing antipsychotic treatment in patients with schizophrenia spectrum disorders exhibiting an inflammatory profile. The "Add-on Celecoxib treatment in patients with schizophrenia spectrum disorders and inflammatory cytokine profile trial (TargetFlame)" is a multicentre randomized, placebo-controlled phase III investigator-initiated clinical trial with the following two arms: patients exhibiting an inflammatory profile receiving either add-on Celecoxib 400 mg/day or add-on placebo. A total of 199 patients will be assessed for eligibility by measuring blood levels of three pro-inflammatory cytokines, and 109 patients with an inflammatory profile, i.e. inflamed, will be randomized, treated for 8 weeks and followed-up for additional four months. The primary endpoint will be changes in symptom severity as assessed by total Positive and Negative Syndrome Scale (PANSS) score changes from baseline to week 8. Secondary endpoints include various other measures of psychopathology and safety. Additional health economic analyses will be performed. TargetFlame is the first study aimed at evaluating the efficacy, safety and cost-effectiveness of the antiphlogistic agent Celecoxib in a subset of patients with schizophrenia spectrum disorders exhibiting an inflammatory profile. With TargetFlame, we intended to investigate a novel precision medicine approach towards anti-inflammatory antipsychotic treatment augmentation using drug repurposing. Clinical trial registration: http://www.drks.de/DRKS00029044 and https://trialsearch.who.int/Trial2.aspx?TrialID=DRKS00029044.
Risperidone combination therapy with adalimumab for treatment of chronic schizophrenia: a randomized, double-blind, placebo-controlled clinical trial. [2023]This study aimed to investigate the efficacy and safety of antitumor necrosis factor-alpha (TNF-α) therapy using adalimumab in patients with chronic schizophrenia. This is a randomized, double-blind, placebo-controlled clinical trial carried out at Roozbeh Hospital (Tehran, Iran) from June 2020 to October 2021. The patients were randomly divided into two parallel adalimumab + risperidone and placebo + risperidone groups. Participants in the intervention group received adalimumab subcutaneous injection (40 mg) by pen-injector at weeks 0 and 4. Using the Positive and Negative Symptoms Scale (PANSS), patients' positive and negative symptoms were assessed at weeks 0, 4, and 8. Forty patients (20 in each group) were included. PANSS total (t = 4.43, df = 38, P 0.05 for all). The current study found adalimumab adjunctive therapy effective in treating schizophrenia, particularly its negative and general psychopathology symptoms, with no side effects.
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]Methotrexate is a commonly used anti-inflammatory and immunosuppressive drug. There is growing evidence that inflammatory processes are involved in the pathogenesis of schizophrenia. In our recent randomised double-blind placebo-controlled clinical trial in Pakistan and Brazil, the addition of minocycline (antibiotic and anti-inflammatory drug) for 1 year to treatment as usual reduced negative symptoms and improved some cognitive measures. A meta-analysis of cytokine changes in the peripheral blood has identified IL-2, IFN-gamma, TNF-alpha and soluble IL-2 receptor as trait markers of schizophrenia because their levels were elevated during acute exacerbations and reduced in remission. This suggests immune activation and an inflammatory syndrome in schizophrenia. Based on the evidence of the strong anti-inflammatory properties of methotrexate, we propose that low-dose methotrexate may be an effective therapy in early schizophrenia.
Infliximab-induced Depression and Suicidal Behavior in Adolescent with Crohn's Disease: Case Report and Review of Literature. [2022]Infliximab, an anti-inflammatory agent, is used to treat various autoimmune disorders. There are at least 3 reports of severe psychiatric adverse effects of the drug, including suicidal behaviors in adults and psychosis in adult and adolescent patients. We report a case of an adolescent who developed depression and suicidal behaviors shortly after beginning infliximab. Although there have been reports of adolescents developing acute psychosis shortly after starting infliximab, this is, to our knowledge, the first report of adolescent suicidal behavior in the setting of infliximab treatment.
An update on the efficacy of anti-inflammatory agents for patients with schizophrenia: a meta-analysis. [2020]Accumulating evidence shows that a propensity towards a pro-inflammatory status in the brain plays an important role in schizophrenia. Anti-inflammatory drugs might compensate this propensity. This study provides an update regarding the efficacy of agents with some anti-inflammatory actions for schizophrenia symptoms tested in randomized controlled trials (RCTs).