An Open-Label Trial of Tocilizumab in Schizophrenia
Condition: Schizophrenia
MeSH terms: Schizophrenia
Intervention: Tocilizumab
Intervention description: 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.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: No
Keywords: tocilizumab; safety; tolerability; efficacy; schizophrenia; improvement; cognition; psychotic symptoms; baseline IL-6 levels

Summary:

      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.
    

Eligibility criteria:

        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