NCT02449746

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
10

participants targeted

Target at below P25 for not_applicable schizophrenia

Timeline
Completed

Started Aug 2015

Geographic Reach
1 country

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 13, 2015

Completed
7 days until next milestone

First Posted

Study publicly available on registry

May 20, 2015

Completed
2 months until next milestone

Study Start

First participant enrolled

August 1, 2015

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2017

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2017

Completed
Last Updated

February 19, 2018

Status Verified

February 1, 2018

Enrollment Period

2 years

First QC Date

May 13, 2015

Last Update Submit

February 15, 2018

Conditions

Keywords

SchizophreniaPsychosisMental HealthAutoimmunityPsychoneuroimmunology

Outcome Measures

Primary Outcomes (1)

  • 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

    2 weeks

Study Arms (2)

Intravenous Immunoglobulin (IVIG)

ACTIVE COMPARATOR

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.

Biological: Intravenous immunoglobulin

Plasma Pheresis / Plasma Exchange (PLEX)

ACTIVE COMPARATOR

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

Biological: Plasma Exchange

Interventions

Plasma ExchangeBIOLOGICAL

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.

Also known as: PLEX
Plasma Pheresis / Plasma Exchange (PLEX)

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.

Also known as: IVIG
Intravenous Immunoglobulin (IVIG)

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

University Hospitals Birmingham

Birmingham, United Kingdom

Location

Cambridge University Hospitals

Cambridge, United Kingdom

Location

Nottingham University Hospitals

Nottingham, United Kingdom

Location

Oxford University Hospitals

Oxford, United Kingdom

Location

University Hospitals Southampton

Southampton, United Kingdom

Location

MeSH Terms

Conditions

SchizophreniaPsychotic DisordersPsychological Well-BeingAutoimmune Diseases

Interventions

Plasma ExchangeImmunoglobulins, Intravenous

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic DisordersMental DisordersPersonal SatisfactionBehaviorImmune System Diseases

Intervention Hierarchy (Ancestors)

Blood TransfusionBiological TherapyTherapeuticsPlasmapheresisBlood Component RemovalSorption DetoxificationExtracorporeal CirculationSurgical Procedures, OperativeImmunoglobulin GImmunoglobulin IsotypesAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Alasdair Coles, 01223 762016

    ajc1020@medschl.cam.ac.uk

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Masking Details
open label
Purpose
OTHER
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Prof Rev Alasdair Coles, Principal Investigator

Study Record Dates

First Submitted

May 13, 2015

First Posted

May 20, 2015

Study Start

August 1, 2015

Primary Completion

August 1, 2017

Study Completion

December 1, 2017

Last Updated

February 19, 2018

Record last verified: 2018-02

Locations