Intravenous immunoglobulin and rituximab versus placebo treatment of antibody-associated psychosis: study protocol of a randomised phase IIa double-blinded placebo-controlled trial (SINAPPS2)
Abstract Background Evidence is conflicting about a causal role of inflammation in psychosis and, specifically, regarding antibodies binding to neuronal membrane targets, especially N-methyl-D-aspartate receptors. NMDAR, LGI1 and GABA-A antibodies were found more prevalent in people with psychosis t...
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BMC
2019-06-01
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Series: | Trials |
Online Access: | http://link.springer.com/article/10.1186/s13063-019-3336-1 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Belinda Lennox Ksenija Yeeles Peter B. Jones Michael Zandi Eileen Joyce Ly-Mee Yu Giuliano Tomei Rebecca Pollard Sally-Anne Vincent Mio Shimazaki Iona Cairns Francis Dowling Thomas Kabir Thomas R. E. Barnes Anne Lingford Hughes Akram A. Hosseini Timothy Harrower Camilla Buckley Alasdair Coles |
spellingShingle |
Belinda Lennox Ksenija Yeeles Peter B. Jones Michael Zandi Eileen Joyce Ly-Mee Yu Giuliano Tomei Rebecca Pollard Sally-Anne Vincent Mio Shimazaki Iona Cairns Francis Dowling Thomas Kabir Thomas R. E. Barnes Anne Lingford Hughes Akram A. Hosseini Timothy Harrower Camilla Buckley Alasdair Coles 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 |
author_facet |
Belinda Lennox Ksenija Yeeles Peter B. Jones Michael Zandi Eileen Joyce Ly-Mee Yu Giuliano Tomei Rebecca Pollard Sally-Anne Vincent Mio Shimazaki Iona Cairns Francis Dowling Thomas Kabir Thomas R. E. Barnes Anne Lingford Hughes Akram A. Hosseini Timothy Harrower Camilla Buckley Alasdair Coles |
author_sort |
Belinda Lennox |
title |
Intravenous immunoglobulin and rituximab versus placebo treatment of antibody-associated psychosis: study protocol of a randomised phase IIa double-blinded placebo-controlled trial (SINAPPS2) |
title_short |
Intravenous immunoglobulin and rituximab versus placebo treatment of antibody-associated psychosis: study protocol of a randomised phase IIa double-blinded placebo-controlled trial (SINAPPS2) |
title_full |
Intravenous immunoglobulin and rituximab versus placebo treatment of antibody-associated psychosis: study protocol of a randomised phase IIa double-blinded placebo-controlled trial (SINAPPS2) |
title_fullStr |
Intravenous immunoglobulin and rituximab versus placebo treatment of antibody-associated psychosis: study protocol of a randomised phase IIa double-blinded placebo-controlled trial (SINAPPS2) |
title_full_unstemmed |
Intravenous immunoglobulin and rituximab versus placebo treatment of antibody-associated psychosis: study protocol of a randomised phase IIa double-blinded placebo-controlled trial (SINAPPS2) |
title_sort |
intravenous immunoglobulin and rituximab versus placebo treatment of antibody-associated psychosis: study protocol of a randomised phase iia double-blinded placebo-controlled trial (sinapps2) |
publisher |
BMC |
series |
Trials |
issn |
1745-6215 |
publishDate |
2019-06-01 |
description |
Abstract Background Evidence is conflicting about a causal role of inflammation in psychosis and, specifically, regarding antibodies binding to neuronal membrane targets, especially N-methyl-D-aspartate receptors. NMDAR, LGI1 and GABA-A antibodies were found more prevalent in people with psychosis than in healthy controls. We aim to test whether these antibodies are pathogenic and may cause isolated psychosis. The SINAPPS2 phase IIa double-blinded randomised controlled trial will test the efficacy and safety of immunoglobulin and rituximab treatment versus placebo for patients with acute psychosis symptoms as added to psychiatric standard of care. Methods We will screen approximately 2500 adult patients with acute psychosis to identify 160 with antibody-positive psychosis without co-existing neurological disease and recruit about 80 eligible participants to the trial in the period from September 2017 to September 2021 across the UK. Eligible patients will be randomised 1:1 either to intravenous immunoglobulin (IVIG) followed by rituximab or to placebo infusions of 1% albumin followed by 0.9% sodium chloride, respectively. To detect a time-to-symptomatic-recovery hazard ratio of 0.322 with a power of 80%, 56 participants are needed to complete the trial, allowing for up to 12 participants to drop out of each group. Eligible patients will be randomised and assessed at baseline within 4 weeks of their eligibility confirmation. The treatment will start with IVIG or 1% albumin placebo infusions over 2–4 consecutive days no later than 7 days from baseline. It will continue 4–5 weeks later with a rituximab or sodium chloride placebo infusion and will end 2–3 weeks after this with another rituximab or placebo infusion. The primary outcome is the time to symptomatic recovery defined as symptomatic remission sustained for at least 6 months on the following Positive and Negative Syndrome Scale items: P1, P2, P3, N1, N4, N6, G5 and G9. Participants will be followed for 12 months from the first day of treatment or, where sustained remission begins after the first 6 months, for an additional minimum of 6 months to assess later response. Discussion The SINAPPS2 trial aims to test whether immunotherapy is efficacious and safe in psychosis associated with anti-neuronal membrane antibodies. Trial registration ISRCTN, 11177045. Registered on 2 May 2017. EudraCT, 2016-000118-31. Registered on 22 November 2016. ClinicalTrials.gov, NCT03194815. Registered on 21 June 2017. |
url |
http://link.springer.com/article/10.1186/s13063-019-3336-1 |
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doaj-680f20e461b947d291e244f28a825ed92020-11-25T03:19:51ZengBMCTrials1745-62152019-06-0120111210.1186/s13063-019-3336-1Intravenous immunoglobulin and rituximab versus placebo treatment of antibody-associated psychosis: study protocol of a randomised phase IIa double-blinded placebo-controlled trial (SINAPPS2)Belinda Lennox0Ksenija Yeeles1Peter B. Jones2Michael Zandi3Eileen Joyce4Ly-Mee Yu5Giuliano Tomei6Rebecca Pollard7Sally-Anne Vincent8Mio Shimazaki9Iona Cairns10Francis Dowling11Thomas Kabir12Thomas R. E. Barnes13Anne Lingford Hughes14Akram A. Hosseini15Timothy Harrower16Camilla Buckley17Alasdair Coles18Department of Psychiatry, University of Oxford and Oxford Health NHS Foundation Trust, Warneford HospitalDepartment of Psychiatry, University of Oxford and Oxford Health NHS Foundation Trust, Warneford HospitalSchool of Clinical Medicine and Department of Psychiatry, University of CambridgeDepartment of Neuromuscular Diseases, University College London Queen Square Institute of Neurology, and National Hospital for Neurology and NeurosurgeryUniversity College London Institute of Neurology, The National Hospital for Neurology and NeurosurgeryPrimary Care Clinical Trials Unit, Nuffield Department of Primary Care Health Sciences, University of OxfordDepartment of Psychiatry, University of Oxford and Oxford Health NHS Foundation Trust, Warneford HospitalDepartment of Psychiatry, University of Oxford and Oxford Health NHS Foundation Trust, Warneford HospitalDepartment of Psychiatry, University of Oxford and Oxford Health NHS Foundation Trust, Warneford HospitalDepartment of Psychiatry, University of Oxford and Oxford Health NHS Foundation Trust, Warneford HospitalResearch and Development, Devon Partnerships NHS Foundation TrustCambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation TrustThe McPin FoundationDepartment of Medicine, The Centre for Psychiatry, Imperial College LondonCentre for Psychiatry, Imperial College LondonDepartment of Neurology, Queen’s Medical Centre, Nottingham University Hospitals NHS TrustRoyal Devon and Exeter Hospital, Royal Devon and Exeter NHS Foundation TrustNuffield Department of Clinical Neurosciences, Oxford University Hospitals NHS Foundation TrustDepartment of Clinical Neurosciences, University of CambridgeAbstract Background Evidence is conflicting about a causal role of inflammation in psychosis and, specifically, regarding antibodies binding to neuronal membrane targets, especially N-methyl-D-aspartate receptors. NMDAR, LGI1 and GABA-A antibodies were found more prevalent in people with psychosis than in healthy controls. We aim to test whether these antibodies are pathogenic and may cause isolated psychosis. The SINAPPS2 phase IIa double-blinded randomised controlled trial will test the efficacy and safety of immunoglobulin and rituximab treatment versus placebo for patients with acute psychosis symptoms as added to psychiatric standard of care. Methods We will screen approximately 2500 adult patients with acute psychosis to identify 160 with antibody-positive psychosis without co-existing neurological disease and recruit about 80 eligible participants to the trial in the period from September 2017 to September 2021 across the UK. Eligible patients will be randomised 1:1 either to intravenous immunoglobulin (IVIG) followed by rituximab or to placebo infusions of 1% albumin followed by 0.9% sodium chloride, respectively. To detect a time-to-symptomatic-recovery hazard ratio of 0.322 with a power of 80%, 56 participants are needed to complete the trial, allowing for up to 12 participants to drop out of each group. Eligible patients will be randomised and assessed at baseline within 4 weeks of their eligibility confirmation. The treatment will start with IVIG or 1% albumin placebo infusions over 2–4 consecutive days no later than 7 days from baseline. It will continue 4–5 weeks later with a rituximab or sodium chloride placebo infusion and will end 2–3 weeks after this with another rituximab or placebo infusion. The primary outcome is the time to symptomatic recovery defined as symptomatic remission sustained for at least 6 months on the following Positive and Negative Syndrome Scale items: P1, P2, P3, N1, N4, N6, G5 and G9. Participants will be followed for 12 months from the first day of treatment or, where sustained remission begins after the first 6 months, for an additional minimum of 6 months to assess later response. Discussion The SINAPPS2 trial aims to test whether immunotherapy is efficacious and safe in psychosis associated with anti-neuronal membrane antibodies. Trial registration ISRCTN, 11177045. Registered on 2 May 2017. EudraCT, 2016-000118-31. Registered on 22 November 2016. ClinicalTrials.gov, NCT03194815. Registered on 21 June 2017.http://link.springer.com/article/10.1186/s13063-019-3336-1 |