An Open-Label Trial of Tocilizumab in Schizophrenia
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Purpose
This study is a Phase 1 clinical trail to determine the safety, tolerability, and efficacy of Tocilizumab (Actemra) as an adjunct to antipsychotic medications in stable outpatients with schizophrenia. Tocilizumab (structural formula C6428H9976N1720O2018S42) is a recombinant humanized anti-human interleukin-6 (IL-6) receptor monoclonal antibody of the immunoglobulin (Ig) gamma-1 subclass. Tocilizumab is formulated as a concentrate for solution for infusion, and will be administered by intravenous infusion.
The investigators propose an 8-week trial to determine the safety, tolerability, and effectiveness of tocilizumab, given in addition to antipsychotic medications, in 10 stable outpatients with schizophrenia. The investigators hypothesize that tocilizumab will be associated with clinically significant improvement in cognition and total psychotic symptoms over the course of the trial. Tocilizumab is administered as an intravenous infusion every 4 weeks. Following a screening evaluation, participants will receive two infusions of tocilizumab, one at baseline and another at week 4 of the study. The investigators will measure changes in cognitive function and symptoms over an 8-week period. Complementing previous positive clinical trials of non-steroidal anti-inflammatory drugs, this would be a "proof-of-concept" study that targeting specific cytokines is a viable treatment for schizophrenia.
Interleukin 6 and its receptor were discovered and cloned at Osaka University, Japan, by Tadamitsu Kishimoto in the 1980s. In 1997, Chugai Pharmaceuticals began the clinical development of tocilizumab for the treatment of rheumatoid arthritis. Clinical studies for Castleman's disease and systemic juvenile idiopathic arthritis started in 2001 and 2002, respectively. Hoffmann-La Roche co-developed the drug due to a license agreement in 2003.
Data presented in 2008 showed the effectiveness of tocilizumab in combination therapy with methotrexate for rheumatoid arthritis treatment. In further studies, it was effective and generally well tolerated when administered either as monotherapy or in combination with conventional disease-modifying antirheumatic drugs in adult patients with moderate to severe rheumatoid arthritis.
| Condition | Intervention | Phase |
|---|---|---|
|
Schizophrenia |
Drug: Tocilizumab |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | An Open-Label Trial of Tocilizumab in Schizophrenia |
- Change in Cognition [ Time Frame: Change in BACS composite score from baseline to 8 weeks ] [ Designated as safety issue: No ]The Brief Assessment of Cognition in Schizophrenia (BACS) is the metric used to characterize cognition in this study. The BACS consists of 6 subscales: Verbal Memory (range 0-75), Working Memory (range 0-28), Motor Speed (range 0-100), Verbal Fluency (measure is total number of words generated in two 60 second trials), Attention and Processing speed (range 0-110), and Executive Function (range 0-22). For each subscale, higher scores reflect better cognition. For each subscale, a Standard Deviation Score was calculated based on normative data (Keefe et al. Norms and standardization of the Brief Assessment of Cognition in Schizophrenia (BACS). Schizophrenia Research 102 (2008) 108-115). The BACS composite score is calculated as the average Standard Deviation Score of the 6 subscale scores. The change in BACS composite score was calculated as the BACS composite score at 8 weeks minus the BACS composite score at baseline.
- Change in Total Psychotic Symptoms [ Time Frame: Change in PANSS total score from baseline to 8 weeks ] [ Designated as safety issue: No ]The Positive and Negative Symptoms Scale (PANSS) is the metric used to characterize psychotic symptoms in this study. The PANSS consists of 30 items, each scored 1-7. The range for the PANSS total score is 30-210. There are 3 subscales - PANSS positive score (range 7-49), PANSS negative score (range 7-49), and PANSS general score (range 16-112). PANSS total score is the summation of these 3 subscales. Higher values for the total and subscale scores reflect more severe psychopathology. A positive change in PANSS total score reflects an increase in psychopathology. A negative change in PANSS total score reflects a decrease in psychopathology.
| Enrollment: | 8 |
| Study Start Date: | September 2012 |
| Study Completion Date: | December 2014 |
| Primary Completion Date: | December 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Tocilizumab
Following a screening evaluation, participants will receive two infusions of tocilizumab, one at baseline and another at week 4 of the study. All subjects will receive a 4 mg/kg infusion of tocilizumab, the recommended starting dose for adults with rheumatoid arthritis.
|
Drug: Tocilizumab
Therapeutic/Pharmacologic Class of Drug: Tocilizumab is a recombinant humanized anti-human interleukin-6 (IL-6) receptor monoclonal antibody of the immunoglobulin (Ig) gamma-1 subclass. Type of Dosage Form: Concentrate for solution for infusion. Route of Administration: Intravenous (i.v.) infusion. Other Names:
|
Show Detailed Description
Eligibility| Ages Eligible for Study: | 18 Years to 50 Years (Adult) |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- male and female
- age 18-50
- capable of giving informed consent
- diagnosis of schizophrenia
- stable based on clinical judgement, no psychiatric hospitalizations in past 3 months, and on the same psychotropic medications for >4 weeks
- taking a non-clozapine antipsychotic
Exclusion Criteria:
- imminent danger to self/others
- antibiotic use in the past 2 weeks
- current scheduled use of immunomodulatory agents
- history of an immune disorder
- illicit drug use in the past 30 days
- any unstable or untreated medical condition
- history of gastrointestinal ulcers, diverticulitis, malignancy, central nervous system demyelinating disorder, seizure disorder, or tuberculosis
- low absolute neutrophil (<2000) or platelet (<100,000) count
- abnormal hepatic (AST or ALT >1.5 times the upper limit of normal) or renal (BUN or creatinine>1.5 times the upper limit of normal) function
- any abnormal lab test result judged to be clinically significant
- active, chronic or recurrent infections
- pregnancy
- breastfeeding
- female and of child-bearing potential who is not using any contraception
Contacts and LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT01696929
| United States, Georgia | |
| Georgia Health Sciences University | |
| Augusta, Georgia, United States, 30912 | |
| Principal Investigator: | Brian Miller, MD, PhD, MPH | Georgia Health Sciences University Department of Psychiatry and Health Behavior |
More Information
Publications:
| Responsible Party: | Brian Miller, Assistant Professor, Georgia Regents University |
| ClinicalTrials.gov Identifier: | NCT01696929 History of Changes |
| Other Study ID Numbers: | Pro00000405 |
| Study First Received: | September 24, 2012 |
| Results First Received: | August 5, 2015 |
| Last Updated: | June 23, 2016 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by Augusta University:
|
tocilizumab safety tolerability efficacy schizophrenia |
improvement cognition psychotic symptoms baseline IL-6 levels |
Additional relevant MeSH terms:
|
Schizophrenia Schizophrenia Spectrum and Other Psychotic Disorders Mental Disorders |
ClinicalTrials.gov processed this record on September 30, 2016