Study of Immunotherapy in Autoantibody Positive Psychosis

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.

Conditions

• Schizophrenia
• Psychosis
• Auto Immune Disorders

Interventions

BIOLOGICAL

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 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.

BIOLOGICAL

Intravenous immunoglobulin

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.

Sponsors & Collaborators

• University of Oxford

  collaborator OTHER

• Stanley Medical Research Institute

  collaborator OTHER

• McPin Foundation

  collaborator OTHER

• University of Cambridge

  lead OTHER

Principal Investigators

• Alasdair Coles, 01223 762016 · [email protected]

Study Design

Allocation

RANDOMIZED

Purpose

OTHER

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2015-08-31

Primary Completion

2017-08-31

Completion

2017-12-31

Countries

• United Kingdom

Study Locations