NCT03194815

Brief Summary

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.

Trial Health

77
On Track

Trial Health Score

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

Enrollment
70

participants targeted

Target at P50-P75 for phase_2

Timeline
11mo left

Started Nov 2017

Longer than P75 for phase_2

Geographic Reach
1 country

10 active sites

Status
recruiting

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

Study Progress90%
Nov 2017Mar 2027

First Submitted

Initial submission to the registry

February 2, 2017

Completed
5 months until next milestone

First Posted

Study publicly available on registry

June 21, 2017

Completed
4 months until next milestone

Study Start

First participant enrolled

November 1, 2017

Completed
9.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 31, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 31, 2027

Last Updated

March 30, 2025

Status Verified

March 1, 2025

Enrollment Period

9.4 years

First QC Date

February 2, 2017

Last Update Submit

March 25, 2025

Conditions

Keywords

PsychosisImmunotherapyAutoantibodies

Outcome Measures

Primary Outcomes (1)

  • 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

Secondary Outcomes (11)

  • Time to first treatment response (whether sustained or not)

    up to 18 months

  • Relapse rate

    18 months

  • Number of adverse effects

    18 months

  • Proportion of patients reaching 20% reduction in PANSS total score

    12 months

  • Proportion of patients reaching 30% reduction in PANSS total score

    12 months

  • +6 more secondary outcomes

Study Arms (2)

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.

Drug: Intravenous immunoglobulinDrug: Rituximab

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.

Drug: Placebo

Interventions

This is a blood product containing antibodies from thousands of healthy donors.

Also known as: IVIG, Intratect
Intravenous immunoglobulin and Rituximab

This is the control, or sham, treatment

Also known as: Saline solution
Placebo

Rituximab is a type of biological therapy. It removes B-cells and helps to reduce the inflammation

Also known as: MabThera
Intravenous immunoglobulin and Rituximab

Eligibility Criteria

Age16 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Acute psychosis \>2 weeks. This may either be first episode or relapse after remission (remission defined as having mild or absent symptoms of psychosis for at least 6 months)
  • Serum or CSF neuronal membrane autoantibodies at pathological levels (including NMDAR, LGI1 and other)
  • Psychosis symptoms as defined by PANSS ≥4 on at least one of the following items: P1, P2, P3, N1, N4, N6, G5 and G9.

You may not qualify if:

  • Current episode of psychosis greater than 24 months duration
  • Co-existing severe neurological disease
  • Evidence of current acute encephalopathy
  • Hepatitis or HIV infection, pregnancy
  • Contraindications to any trial drug
  • Concurrent enrolment in another CTIMP

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

Cambridge University Hospitals NH Foundation Trust

Cambridge, United Kingdom

RECRUITING

Royal Devon and Exeter NHS Foundation Trust

Exeter, United Kingdom

RECRUITING

NHS Greater Glasgow and Clyde

Glasgow, United Kingdom

RECRUITING

The Walton Centre NHS Foundation Trust

Liverpool, United Kingdom

RECRUITING

University College London Hospitals Nhs Foundation Trust

London, NW1 2PG, United Kingdom

RECRUITING

King's College Hospital NHS Foundation Trust

London, United Kingdom

RECRUITING

Salford Royal NHS Foundation Trust

Manchester, United Kingdom

RECRUITING

Nottingham University Hospitals NHS Trust

Nottingham, United Kingdom

RECRUITING

Oxford University Hospitals NHS Foundation Trust

Oxford, United Kingdom

RECRUITING

Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, United Kingdom

RECRUITING

Related Publications (1)

  • 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.

Related Links

MeSH Terms

Conditions

Psychotic DisordersAutoimmune Diseases of the Nervous System

Interventions

Immunoglobulins, IntravenousSaline SolutionRituximab

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic DisordersMental DisordersNervous System DiseasesAutoimmune DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin GImmunoglobulin IsotypesAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsCrystalloid SolutionsIsotonic SolutionsSolutionsPharmaceutical PreparationsAntibodies, Monoclonal, Murine-DerivedAntibodies, Monoclonal

Study Officials

  • Alasdair Coles, PhD FRCP

    University of Cambridge, UK

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Alastdair Coles, PhD FRCP

CONTACT

Belinda Lennox, DM MRCPsych

CONTACT

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Revd. Prof. Alasdair Coles, Chief Investigator

Study Record Dates

First Submitted

February 2, 2017

First Posted

June 21, 2017

Study Start

November 1, 2017

Primary Completion (Estimated)

March 31, 2027

Study Completion (Estimated)

March 31, 2027

Last Updated

March 30, 2025

Record last verified: 2025-03

Locations