IVIG and rituximab in antibody-associated psychosis - SINAPPS2
Research type
Research Study
Full title
A randomised phase II double-blinded placebo-controlled trial of intravenous immunoglobulins and rituximab in patients with antibody-associated psychosis (SINAPPS2)
IRAS ID
198941
Contact name
Alasdair Coles
Contact email
Sponsor organisation
Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge
Eudract number
2016-000118-31
Duration of Study in the UK
4 years, 11 months, 31 days
Research summary
Psychosis and schizophrenia are caused by factors associated with excess dopamine and abnormally low N-methyl D-aspartate receptor (NMDAR) functioning. There is increasing evidence for the role of inflammation in these disorders. We propose that one possible cause of psychosis and schizophrenia is the presence of antibodies in the blood that bind to the neuronal membrane in the brain. Since discovery of antibodies that bind to the NMDAR (NMDAR-ab) that cause encephalitis, we have discovered NMDAR-ab or voltage-gated potassium channel complex antibodies (VGKC-ab) in 6.5% of first episode psychosis (FEP) patients, without signs of encephalitis. This was replicated in an on-going MRC-funded study, where 8.8% of FEP patients possessed these autoantibodies.
Open-label experience suggests immunotherapy is effective in cases of full antibody-encephalitis. We recently reported on 18 patients with NMDAR-ab; 9 resolved on their own, or responded to antipsychotics, and 9 were resistant to up to 3 antipsychotics. Antipsychotic resistant patients were treated with corticosteroids alongside immunotherapy (plasma exchange (PLEX) or intravenous immunoglobulin (IVIG; a blood product containing antibodies), with subsequent mycophenolate or rituximab treatment), and responded well.
Informed by our feasibility study, this randomised double-blinded placebo-controlled trial aims to test the hypothesis that immunotherapy is an effective treatment for antibody-associated psychosis, either in FEP or relapse following remission, alongside antipsychotic medication if required. Trial immunotherapy consists of IVIG
(2g/kg over 4 days) followed by two infusions of 1g rituximab(~day 30, then 14 days after the first infusion). This trial combines a rapid-action treatment (IVIG) to induce symptom remission, with a longer-action therapy (rituximab) to maintain remission.
Before treatment, a number of assessments will be performed, including physician review and examination, laboratory investigations (including Ab-assays and safety blood tests and storing serum for future research), as well as clinical and cognitive assessments.REC name
South Central - Oxford C Research Ethics Committee
REC reference
16/SC/0584
Date of REC Opinion
6 Dec 2016
REC opinion
Favourable Opinion