IVIG and Rituximab in Antibody-associated Psychosis - SINAPPS2
- Conditions
- Autoimmune EncephalitisPsychosis
- Interventions
- Registration Number
- NCT03194815
- Lead Sponsor
- University of Cambridge
- Brief Summary
A randomised phase II double-blinded placebo-controlled trial designed to explore the utility of immunotherapy for patients with acute psychosis associated with anti-neuronal membranes (NMDA-receptor or Voltage Gated Potassium Channel).
Primary objective: To test the efficacy of immunotherapy (IVIG and rituximab) for patients with acute psychosis associated with anti-neuronal membranes.
Secondary objective: To test safety of immunotherapy (IVIG and rituximab) for patients with acute psychosis associated with anti-neuronal membranes.
- Detailed Description
Investigators propose 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: 2g/kg over days 1-4) followed by two infusions of 1g rituximab (at day 28-35, and then 14 days after the first infusion). 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. It is based on a protocol where elimination of circulating antibodies is the treatment goal, namely "desensitisation" of potential transplant patients who have multiple anti-HLA antibodies capable of inducing hyperacute rejection and also being tested in various trials on clinicaltrials.gov (NCT00642655, NCT01178216, and NCT01502267). Blinding is required to minimise placebo responses in a trial based on symptomatology.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 70
- Acute psychosis >2 weeks. This may either be first episode or relapse after remission (remission defined as having mild or absent symptoms of psychosis for at least 6 months)
- Serum or CSF neuronal membrane autoantibodies at pathological levels (including NMDAR, LGI1 and other)
- Psychosis symptoms as defined by PANSS ≥4 on at least one of the following items: P1, P2, P3, N1, N4, N6, G5 and G9.
- Current episode of psychosis greater than 24 months duration
- Co-existing severe neurological disease
- Evidence of current acute encephalopathy
- Hepatitis or HIV infection, pregnancy
- Contraindications to any trial drug
- Concurrent enrolment in another CTIMP
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Intravenous immunoglobulin and Rituximab Intravenous immunoglobulin One cycle of intravenous immunoglobulin (IVIG) 2g/kg over 2-5 days (days 1-5) followed by (b) two infusions of 1g rituximab (the first infusion starting between days 28-35, and the second infusion 14 days later), each with 100mg methylprednisolone. Placebo Placebo One cycle of 0.9% saline solution over 2-5 days (days 1-5) followed by (b) two infusions of placebo solution alongside placebo pill - in equal volumes to steroid pre-medication and rituximab. Intravenous immunoglobulin and Rituximab Rituximab One cycle of intravenous immunoglobulin (IVIG) 2g/kg over 2-5 days (days 1-5) followed by (b) two infusions of 1g rituximab (the first infusion starting between days 28-35, and the second infusion 14 days later), each with 100mg methylprednisolone.
- Primary Outcome Measures
Name Time Method Time to start of symptomatic recovery (symptomatic remission sustained for at least 6 months) up to 18 months remission defined as Positive and Negative Syndrome Scale (PANSS) score 3 or less on PANSS items P1, P2, P3, N1, N4, N6, G5 and G9 sustained for 6 months
- Secondary Outcome Measures
Name Time Method Changes in the Clinical Global Impression Scale in Schizophrenia (CGI-Schizophrenia) 12 months Change in CGI-Schizophrenia scores from baseline to month 12
Time to first treatment response (whether sustained or not) up to 18 months Treatment response defined as score of 3 or less on each of the following PANSS items: P1, P2, P3, N1, N4, N6, G5, and G9.
Number of adverse effects 18 months total number of patient reported adverse effects
Changes in the Brief Assessment of Cognition in Schizophrenia (BACS) 12 months Change in BACS scores from baseline to month 12
Changes in the Global Assessment of Functioning scale (GAF) 12 months Change in the GAF score from baseline to month 12
Relapse rate 18 months Relapse rate is defined as a score 4 or more on PANSS items P1, P2, P3, N1, N4, N6, G5, and G9.
Proportion of patients reaching 20% reduction in PANSS total score 12 months 20% reduction in the PANSS total score (all PANNS items included)
Proportion of patients reaching 30% reduction in PANSS total score 12 months 30% reduction in the PANSS total score (all PANNS items included)
Changes in the Antipsychotic Non-Neurological Side-Effects Rating Scale (ANNSERS) 12 months Change in ANNSERS total score from baseline to month 12
Proportion of patients reaching 40% reduction in PANSS total score 12 months 40% reduction in the PANSS total score (all PANNS items included)
Changes in the Young Mania Rating Scale (YMRS) 12 months Change in YMRS total score from baseline to month 12
Trial Locations
- Locations (10)
University College London Hospitals Nhs Foundation Trust
🇬🇧London, United Kingdom
Cambridge University Hospitals NH Foundation Trust
🇬🇧Cambridge, United Kingdom
The Walton Centre NHS Foundation Trust
🇬🇧Liverpool, United Kingdom
Salford Royal NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Nottingham University Hospitals NHS Trust
🇬🇧Nottingham, United Kingdom
Oxford University Hospitals NHS Foundation Trust
🇬🇧Oxford, United Kingdom
King's College Hospital NHS Foundation Trust
🇬🇧London, United Kingdom
Royal Devon and Exeter NHS Foundation Trust
🇬🇧Exeter, United Kingdom
NHS Greater Glasgow and Clyde
🇬🇧Glasgow, United Kingdom
Sheffield Teaching Hospitals NHS Foundation Trust
🇬🇧Sheffield, United Kingdom