IVIG and Rituximab in Antibody-associated Psychosis - SINAPPS2

NCT ID: NCT03194815

Last Updated: 2025-03-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

70 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-11-01

Study Completion Date

2027-03-31

Brief Summary

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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.

Detailed Description

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Investigators propose a randomised double-blinded placebo-controlled trial to test the hypothesis that immunotherapy is an effective treatment of antibody-associated psychosis, either first episode of psychosis or relapse following previous remission. Immunotherapy for the trial consists of one cycle of intravenous immunoglobulin (IVIG: 2g/kg over days 1-4) followed by two infusions of 1g rituximab (at day 28-35, and then 14 days after the first infusion). The rationale for this regime is that it combines a rapid-action treatment (IVIG) to induce remission with a longer-action therapy (rituximab) to maintain remission. It is based on a protocol where elimination of circulating antibodies is the treatment goal, namely "desensitisation" of potential transplant patients who have multiple anti-HLA antibodies capable of inducing hyperacute rejection and also being tested in various trials on clinicaltrials.gov (NCT00642655, NCT01178216, and NCT01502267). Blinding is required to minimise placebo responses in a trial based on symptomatology.

Conditions

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Psychosis Autoimmune Encephalitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Intravenous immunoglobulin and Rituximab

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.

Group Type ACTIVE_COMPARATOR

Intravenous immunoglobulin

Intervention Type DRUG

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

Rituximab

Intervention Type DRUG

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

Placebo

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

This is the control, or sham, treatment

Interventions

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Intravenous immunoglobulin

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

Intervention Type DRUG

Placebo

This is the control, or sham, treatment

Intervention Type DRUG

Rituximab

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

Intervention Type DRUG

Other Intervention Names

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IVIG Intratect Saline solution MabThera

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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
Minimum Eligible Age

16 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Oxford

OTHER

Sponsor Role collaborator

University of Cambridge

OTHER

Sponsor Role lead

Responsible Party

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Alasdair Coles

Revd. Prof. Alasdair Coles, Chief Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Alasdair Coles, PhD FRCP

Role: PRINCIPAL_INVESTIGATOR

University of Cambridge, UK

Locations

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Cambridge University Hospitals NH Foundation Trust

Cambridge, , United Kingdom

Site Status RECRUITING

Royal Devon and Exeter NHS Foundation Trust

Exeter, , United Kingdom

Site Status RECRUITING

NHS Greater Glasgow and Clyde

Glasgow, , United Kingdom

Site Status RECRUITING

The Walton Centre NHS Foundation Trust

Liverpool, , United Kingdom

Site Status RECRUITING

University College London Hospitals Nhs Foundation Trust

London, , United Kingdom

Site Status RECRUITING

King's College Hospital NHS Foundation Trust

London, , United Kingdom

Site Status RECRUITING

Salford Royal NHS Foundation Trust

Manchester, , United Kingdom

Site Status RECRUITING

Nottingham University Hospitals NHS Trust

Nottingham, , United Kingdom

Site Status RECRUITING

Oxford University Hospitals NHS Foundation Trust

Oxford, , United Kingdom

Site Status RECRUITING

Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Alastdair Coles, PhD FRCP

Role: CONTACT

+44 (0)1223 762016

Belinda Lennox, DM MRCPsych

Role: CONTACT

: +44(0)1865 613145

Facility Contacts

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Alasdair Coles, PhD FRCP

Role: primary

+44 (0)1223 762016

Timothy Harrower, FRCP PhD

Role: primary

John Goodfellow, MRCP(Neurology), PhD

Role: primary

Saif Huda, MRCP DPhil

Role: primary

Michael Zandi, PhD MRCP

Role: primary

Ester Coutinho, MD, DPhil

Role: primary

Nazar Sharaf, PhD MRCP

Role: primary

Akram Hosseini, MD MRCP PhD

Role: primary

Belinda Lennox, DM MRCPsych

Role: primary

: +44(0)1865 613145

Priya D Shanmugarajah, MD

Role: primary

References

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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.

Reference Type DERIVED
PMID: 31174586 (View on PubMed)

Related Links

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http://sinapps.org.uk

SINAPPS Group website

Other Identifiers

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SINAPPS 2

Identifier Type: -

Identifier Source: org_study_id

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