IVIG and Rituximab in Antibody-associated Psychosis - SINAPPS2

Psychosis Clinical Trial

— SINAPPS2  

Official title:

A Randomised Phase II Double-blinded Placebo-controlled Trial of Intravenous Immunoglobulins and Rituximab in Patients With Antibody-associated Psychosis (SINAPPS2)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03194815
• Other study ID #: SINAPPS 2
• Status: Recruiting
• Phase: Phase 2
• Start date: November 1, 2017
• Est. completion date: March 31, 2026

Study information

• Verified date: January 2024
• Source: University of Cambridge
• Contact: Alastdair Coles, PhD FRCP
• Phone: +44 (0)1223 762016
• Email: ajc1020[@]medschl.cam.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: March 31, 2026
• Est. primary completion date: March 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Autoimmune Diseases of the Nervous System
• Autoimmune Encephalitis
• Encephalitis
• Mental Disorders
• Psychosis
• Psychotic Disorders

Intervention

Drug:
• Intravenous immunoglobulin
This is a blood product containing antibodies from thousands of healthy donors.
• Placebo
This is the control, or sham, treatment
• Rituximab
Rituximab is a type of biological therapy. It removes B-cells and helps to reduce the inflammation

Locations

Country	Name	City	State
United Kingdom	Cambridge University Hospitals NH Foundation Trust	Cambridge
United Kingdom	Royal Devon and Exeter NHS Foundation Trust	Exeter
United Kingdom	NHS Greater Glasgow and Clyde	Glasgow
United Kingdom	The Walton Centre NHS Foundation Trust	Liverpool
United Kingdom	King's College Hospital NHS Foundation Trust	London
United Kingdom	University College London Hospitals Nhs Foundation Trust	London
United Kingdom	Salford Royal NHS Foundation Trust	Manchester
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham
United Kingdom	Oxford University Hospitals NHS Foundation Trust	Oxford
United Kingdom	Sheffield Teaching Hospitals NHS Foundation Trust	Sheffield

Sponsors (2)

Lead Sponsor	Collaborator
University of Cambridge	University of Oxford

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Time to first treatment response (whether sustained or not)	Treatment response defined as score of 3 or less on each of the following PANSS items: P1, P2, P3, N1, N4, N6, G5, and G9.	up to 18 months
Secondary	Relapse rate	Relapse rate is defined as a score 4 or more on PANSS items P1, P2, P3, N1, N4, N6, G5, and G9.	18 months
Secondary	Number of adverse effects	total number of patient reported adverse effects	18 months
Secondary	Proportion of patients reaching 20% reduction in PANSS total score	20% reduction in the PANSS total score (all PANNS items included)	12 months
Secondary	Proportion of patients reaching 30% reduction in PANSS total score	30% reduction in the PANSS total score (all PANNS items included)	12 months
Secondary	Proportion of patients reaching 40% reduction in PANSS total score	40% reduction in the PANSS total score (all PANNS items included)	12 months
Secondary	Changes in the Clinical Global Impression Scale in Schizophrenia (CGI-Schizophrenia)	Change in CGI-Schizophrenia scores from baseline to month 12	12 months
Secondary	Changes in the Young Mania Rating Scale (YMRS)	Change in YMRS total score from baseline to month 12	12 months
Secondary	Changes in the Antipsychotic Non-Neurological Side-Effects Rating Scale (ANNSERS)	Change in ANNSERS total score from baseline to month 12	12 months
Secondary	Changes in the Brief Assessment of Cognition in Schizophrenia (BACS)	Change in BACS scores from baseline to month 12	12 months
Secondary	Changes in the Global Assessment of Functioning scale (GAF)	Change in the GAF score from baseline to month 12	12 months

External Links

•   SINAPPS Group website