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| Name | Class |
|---|---|
| University of Oxford | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intravenous immunoglobulin and Rituximab | Active Comparator | 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 Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Intravenous immunoglobulin | Drug | This is a blood product containing antibodies from thousands of healthy donors. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Time to start of symptomatic recovery (symptomatic remission sustained for at least 6 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 | up to 18 months |
| Measure | Description | Time Frame |
|---|---|---|
| Time to first treatment response (whether sustained or not) | 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. | up to 18 months |
| Relapse rate |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Alasdair Coles, PhD FRCP | University of Cambridge, UK | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cambridge University Hospitals NH Foundation Trust | Cambridge | United Kingdom | ||||
| Royal Devon and Exeter NHS Foundation Trust |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31174586 | Derived | Lennox B, Yeeles K, Jones PB, Zandi M, Joyce E, Yu LM, Tomei G, Pollard R, Vincent SA, Shimazaki M, Cairns I, Dowling F, Kabir T, Barnes TRE, Lingford Hughes A, Hosseini AA, Harrower T, Buckley C, Coles A. Intravenous immunoglobulin and rituximab versus placebo treatment of antibody-associated psychosis: study protocol of a randomised phase IIa double-blinded placebo-controlled trial (SINAPPS2). Trials. 2019 Jun 7;20(1):331. doi: 10.1186/s13063-019-3336-1. |
| Label | URL |
|---|---|
| SINAPPS Group website | View source |
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| Placebo | Drug | This is the control, or sham, treatment |
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| Rituximab | Drug | Rituximab is a type of biological therapy. It removes B-cells and helps to reduce the inflammation |
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Relapse rate is defined as a score 4 or more on PANSS items P1, P2, P3, N1, N4, N6, G5, and G9.
| 18 months |
| Number of adverse effects | total number of patient reported adverse effects | 18 months |
| Proportion of patients reaching 20% reduction in PANSS total score | 20% reduction in the PANSS total score (all PANNS items included) | 12 months |
| Proportion of patients reaching 30% reduction in PANSS total score | 30% reduction in the PANSS total score (all PANNS items included) | 12 months |
| Proportion of patients reaching 40% reduction in PANSS total score | 40% reduction in the PANSS total score (all PANNS items included) | 12 months |
| Changes in the Clinical Global Impression Scale in Schizophrenia (CGI-Schizophrenia) | Change in CGI-Schizophrenia scores from baseline to month 12 | 12 months |
| Changes in the Young Mania Rating Scale (YMRS) | Change in YMRS total score from baseline to month 12 | 12 months |
| Changes in the Antipsychotic Non-Neurological Side-Effects Rating Scale (ANNSERS) | Change in ANNSERS total score from baseline to month 12 | 12 months |
| Changes in the Brief Assessment of Cognition in Schizophrenia (BACS) | Change in BACS scores from baseline to month 12 | 12 months |
| Changes in the Global Assessment of Functioning scale (GAF) | Change in the GAF score from baseline to month 12 | 12 months |
| Exeter |
| United Kingdom |
| NHS Greater Glasgow and Clyde | Glasgow | United Kingdom |
| The Walton Centre NHS Foundation Trust | Liverpool | United Kingdom |
| University College London Hospitals Nhs Foundation Trust | London | NW1 2PG | United Kingdom |
| King's College Hospital NHS Foundation Trust | London | 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 |
| Sheffield Teaching Hospitals NHS Foundation Trust | Sheffield | United Kingdom |
| ID | Term |
|---|---|
| D011618 | Psychotic Disorders |
| D020274 | Autoimmune Diseases of the Nervous System |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
| D009422 | Nervous System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D016756 | Immunoglobulins, Intravenous |
| D000077330 | Saline Solution |
| D000069283 | Rituximab |
| ID | Term |
|---|---|
| D007074 | Immunoglobulin G |
| D007132 | Immunoglobulin Isotypes |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
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