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Clinical Trial - SINAPPS-2
A randomised phase II double-blinded placebo-controlled trial of intravenous immunoglobulins and rituximab in patients with antibody-associated psychosis
Psychosis and schizophrenia are caused by genetic and environmental factors, associated with excess mesolimbic and mesocortical dopamine and NMDAR hypofunction . A range of cell surface protein and immune genetic loci are associated with schizophrenia and there is increasing evidence for a role of inflammation in psychosis and schizophrenia.
One cause of psychosis may be antibodies binding to neuronal membrane targets, especially NMDA receptors, in the brain. Such antibodies were first described in 2007 causing an encephalopathy, with psychiatric features. Over two thirds of the people identified at that time responded to immunotherapy. In such patients, isolated psychotic episodes occur in 23/571 (4%), either at presentation (5/571) or relapse (18/571). The hypothesis underlying the trial is that these antibodies are pathogenic and may be responsible for isolated psychosis.
We launched a randomised double-blinded placebo-controlled trial to test the hypothesis that immunotherapy is an effective treatment of antibody-associated psychosis, either first episode of psychosis or relapse following previous remission. Immunotherapy for the trial consists of one cycle of intravenous immunoglobulin (IVIG) followed by two infusions of rituximab. The rationale for this regime is that it combines a rapid-action treatment (IVIG) to induce remission with a longer-action therapy (rituximab) to maintain remission.
IVIG has been used in NMDAR encephalitis extensively – in over 300 published cases, and is effective and safe in other antibody-associated neuroimmunological disorders, including the Guillain-Barré Syndrome (GBS), in which equivalence to PLEX has been demonstrated.
Rituximab has also been used in NMDAR encephalitis, VGKC-antibody-associated psychosis, and other immunological disorders with good effect and a good safety profile.
Recruitment began in July 2017 and the study will run until December 2021. Eligible participants will be initally identified through our PPiP2 screening study.
This trial is funded by the Medical Research Council.
SINAPPS-2 is a large study involving participants from all across England. It will test the efficacy and safety of immunotherapy (IVIG and Rituximab) in people suffering from psychosis with pathogenic antibodies
If you want to know more about the study procedures and the eligibilty criteria, click here