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Study of Immunotherapy in Autoantibody Positive Psychosis (SINAPPS-1)

Primary Purpose

Schizophrenia, Psychosis, Auto Immune Disorders

Status
Completed
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Plasma Exchange
Intravenous immunoglobulin
Sponsored by
University of Cambridge
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Schizophrenia focused on measuring Schizophrenia, Psychosis, Mental Health, Autoimmunity, Psychoneuroimmunology

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Acute psychosis
  • Serum and/or Cerebrospinal flud (CSF) neuronal membrane autoantibodies (including N-methyl-D-aspartate receptor (NMDAR), Voltage gated potassium channel (VGKC), Leucine-rich, glioma inactivated 1,(LGI1), gamma-aminobutyric acid (GABA [A]) receptor)
  • Positive and Negative Syndrome Scale (PANSS) >4 on items of positive psychotic symptoms

Exclusion Criteria:

  • current symptoms greater than 2 years duration,
  • co-existing severe neurological disease

Sites / Locations

  • University Hospitals Birmingham
  • Cambridge University Hospitals
  • Nottingham University Hospitals
  • Oxford University Hospitals
  • University Hospitals Southampton

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Intravenous Immunoglobulin (IVIG)

Plasma Pheresis / Plasma Exchange (PLEX)

Arm Description

Intravenous Immunoglobulin IVIG is a pooled blood product from 3000-100,000 human blood donors with direct immunomodulatory effects. IVIG will be given at a dose of 2g/kg over 4 days. Dosing at 2g/kg is established in neurological disorders, with limited evidence that lower doses are less effective although adequate dosing studies have not been performed.

Plasma Exchange (PLEX) is a procedure in which the subject's blood is passed through a medical device which separates out plasma from the other blood components, and replaces the plasma with albumin or plasma or other colloid. PLEX therefore removes circulating pathogenic antibodies, and its use was first reported in myasthenia gravis in 1976, and furthermore therapeutic benefit after PLEX supports an antibody mediated pathogenesis of disease. In PLEX, 200-250 mL plasma per kg body weight is exchanged typically over 7-14 days using 5% albumin as replacement, often at alternate days which increases the amount of immunoglobulin removed due to equilibrium effects . PLEX modality (centrifugation or filtration), type of anticoagulation, and dose scheduling will be determined by local centre practice

Outcomes

Primary Outcome Measures

Percentage of patients who start on allocated care pathway within 2 weeks of randomisation.
percentage of recruited patients who start on allocated care pathway within 2 week from randomisation

Secondary Outcome Measures

Full Information

First Posted
May 13, 2015
Last Updated
February 15, 2018
Sponsor
University of Cambridge
Collaborators
University of Oxford, Stanley Medical Research Institute, McPin Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT02449746
Brief Title
Study of Immunotherapy in Autoantibody Positive Psychosis
Acronym
SINAPPS-1
Official Title
An Unblinded Study of the Feasibility of Plasmapheresis or Intravenous Immunoglobulin, Combined With Corticosteroids, in Patients With Acute Psychosis Associated With Anti-neuronal Membrane Auto-antibodies
Study Type
Interventional

2. Study Status

Record Verification Date
February 2018
Overall Recruitment Status
Completed
Study Start Date
August 2015 (Actual)
Primary Completion Date
August 2017 (Actual)
Study Completion Date
December 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Cambridge
Collaborators
University of Oxford, Stanley Medical Research Institute, McPin Foundation

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Psychosis is a mental health problem that causes people to perceive or interpret things differently from those around them, often involving hallucinations or delusions. Psychosis and schizophrenia are common disorders which predominantly affect younger adults. Recently, the investigators discovered that 5-10% of people with psychosis have antibodies in the blood that are capable of targeting the surface of brain cells, specific to the N-methyl-D-aspartate (NMDA) receptor or voltage gated potassium channel complex, which the investigators believe may be causing the problem. Those positive for antibodies may have a problem with their immune system and this may prevent their brain from working normally. This trial aims to test the feasibility of removing or reducing the antibodies in patients' blood, using immunotherapy, and see if this improves symptoms of psychosis. Immunotherapy in this feasibility study will involve giving all patients steroid tablets and half of them will also receive a drug called "intravenous immunoglobulin" whereas the other half will have a procedure called "plasma exchange". The feasibility study is designed to identify which method of immunotherapy is most suitable for use in this patient population. Results from this will inform on the methodology used for a proposed larger randomised control trial.
Detailed Description
An autoimmune disease occurs when a person's immune system begins to respond to normal bodily substances and tissues as if it were foreign or related to disease. There are a number of autoimmune disorders, some of which can affect the brain by targeting the surface of brain cells, for example signalling proteins like the NMDA receptor or voltage gated potassium channel complex. Some cases of encephalitis, a disorder of brain inflammation that can be autoimmune, are caused by these antibodies, but often present with psychotic experiences, such as hallucinations, and may see a psychiatrist at this stage, before they go on to experience seizures and brain swelling, and are seen by a neurologist. These patients are treated with immunotherapy, and after treatment see a reduction in both seizures and psychotic symptoms. Recently the investigators identified patients with psychosis who test positive for these antibodies, but do not go on to experience these other symptoms of encephalitis. It has been suggested that these patients suffer from an autoimmune disorder similar to the encephalitis described above. Small pilot studies in these antibody positive psychosis patients have shown various immunotherapies can reduce both symptoms of psychosis and number of autoantibodies present in their blood. A randomised clinical trial (RCT) is required to confirm this. However a feasibility study is required first to investigate whether it is possible to deliver the immunotherapy treatments in patients with psychosis. The treatments require an infusion over a few hours (IVIG) or an admission to an acute medical ward for several days(plasma exchange). Both may be challenging for people who are paranoid or agitated. The investigators need to assess whether it is possible to deliver these treatments before proceeding to a large scale, clinical trial. This is a multicentre, randomised, uncontrolled, open label feasibility study. Patients with psychosis and a positive blood test for antibodies will be identified from one of 24 recruiting centres across England. They will undergo screening assessment for eligibility (interview with psychiatrist and neurologist and baseline investigations where possible, including MRI, EEG and lumbar puncture) and give informed consent for the study. A further blood sample (10ml) will be taken for future research. 10 Participants will be randomised to one of two clinical care pathways: either an infusion of intravenous immunoglobulins, or plasma exchange treatment. Both groups will receive steroid tablets, and both groups will continue to receive psychiatric treatment, including antipsychotic medication, as normal. At two months after randomisation the research team will speak to the treating clinicians to gather the primary outcome measure which is whether the patient received the allocated treatment within two weeks of allocation. The researchers may also confirm this outcome from the clinical records.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia, Psychosis, Auto Immune Disorders
Keywords
Schizophrenia, Psychosis, Mental Health, Autoimmunity, Psychoneuroimmunology

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Masking Description
open label
Allocation
Randomized
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Intravenous Immunoglobulin (IVIG)
Arm Type
Active Comparator
Arm Description
Intravenous Immunoglobulin IVIG is a pooled blood product from 3000-100,000 human blood donors with direct immunomodulatory effects. IVIG will be given at a dose of 2g/kg over 4 days. Dosing at 2g/kg is established in neurological disorders, with limited evidence that lower doses are less effective although adequate dosing studies have not been performed.
Arm Title
Plasma Pheresis / Plasma Exchange (PLEX)
Arm Type
Active Comparator
Arm Description
Plasma Exchange (PLEX) is a procedure in which the subject's blood is passed through a medical device which separates out plasma from the other blood components, and replaces the plasma with albumin or plasma or other colloid. PLEX therefore removes circulating pathogenic antibodies, and its use was first reported in myasthenia gravis in 1976, and furthermore therapeutic benefit after PLEX supports an antibody mediated pathogenesis of disease. In PLEX, 200-250 mL plasma per kg body weight is exchanged typically over 7-14 days using 5% albumin as replacement, often at alternate days which increases the amount of immunoglobulin removed due to equilibrium effects . PLEX modality (centrifugation or filtration), type of anticoagulation, and dose scheduling will be determined by local centre practice
Intervention Type
Biological
Intervention Name(s)
Plasma Exchange
Other Intervention Name(s)
PLEX
Intervention Description
PLEX is a procedure in which the subject's blood is passed through a medical device which separates out plasma from the other blood components, and replaces the plasma with albumin or plasma or other colloid. PLEX therefore removes circulating pathogenic antibodies, and furthermore therapeutic benefit after PLEX supports an antibody mediated pathogenesis of disease. In PLEX, 200-250 mL plasma per kg body weight is exchanged typically over 7-14 days using 5% albumin as replacement, often at alternate days which increases the amount of immunoglobulin removed due to equilibrium effects. PLEX modality (centrifugation or filtration), type of anticoagulation, and dose scheduling will be determined by local centre practice.
Intervention Type
Biological
Intervention Name(s)
Intravenous immunoglobulin
Other Intervention Name(s)
IVIG
Intervention Description
Active Comparator: Intravenous Immunoglobulin (IVIG) IVIG is a pooled blood product from 3000-100,000 human blood donors with direct immunomodulatory effects. IVIG will be given at a dose of 2g/kg over 4 days. Dosing at 2g/kg is established in neurological disorders, with limited evidence that lower doses are less effective although adequate dosing studies have not been performed.
Primary Outcome Measure Information:
Title
Percentage of patients who start on allocated care pathway within 2 weeks of randomisation.
Description
percentage of recruited patients who start on allocated care pathway within 2 week from randomisation
Time Frame
2 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Acute psychosis Serum and/or Cerebrospinal flud (CSF) neuronal membrane autoantibodies (including N-methyl-D-aspartate receptor (NMDAR), Voltage gated potassium channel (VGKC), Leucine-rich, glioma inactivated 1,(LGI1), gamma-aminobutyric acid (GABA [A]) receptor) Positive and Negative Syndrome Scale (PANSS) >4 on items of positive psychotic symptoms Exclusion Criteria: current symptoms greater than 2 years duration, co-existing severe neurological disease
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alasdair Coles, 01223 762016
Organizational Affiliation
ajc1020@medschl.cam.ac.uk
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospitals Birmingham
City
Birmingham
Country
United Kingdom
Facility Name
Cambridge University Hospitals
City
Cambridge
Country
United Kingdom
Facility Name
Nottingham University Hospitals
City
Nottingham
Country
United Kingdom
Facility Name
Oxford University Hospitals
City
Oxford
Country
United Kingdom
Facility Name
University Hospitals Southampton
City
Southampton
Country
United Kingdom

12. IPD Sharing Statement

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Study of Immunotherapy in Autoantibody Positive Psychosis

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