Clinical trial NCT03194815: IVIG and Rituximab in Antibody-associated Psychosis - SINAPPS2
Official title: A Randomised Phase II Double-blinded Placebo-controlled Trial of Intravenous Immunoglobulins and Rituximab in Patients with Antibody-associated Psychosis (SINAPPS2)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Psychosis
Autoimmune Encephalitis
Keywords: Psychosis
Immunotherapy
Autoantibodies
Lead sponsor: University of Cambridge
Sponsor class: OTHER
Collaborators: name: University of Oxford
First posted: 2017-06-21
Enrollment: 70
Sex: ALL
Minimum age (years): 16
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Time to start of symptomatic recovery (symptomatic remission sustained for at least 6 months)
timeFrame: up to 18 months
Secondary outcomes:
measure: Time to first treatment response (whether sustained or not)
timeFrame: up to 18 months
measure: Relapse rate
timeFrame: 18 months
measure: Number of adverse effects
timeFrame: 18 months
measure: Proportion of patients reaching 20% reduction in PANSS total score
timeFrame: 12 months
measure: Proportion of patients reaching 30% reduction in PANSS total score
timeFrame: 12 months
measure: Proportion of patients reaching 40% reduction in PANSS total score
timeFrame: 12 months
measure: Changes in the Clinical Global Impression Scale in Schizophrenia (CGI-Schizophrenia)
timeFrame: 12 months
measure: Changes in the Young Mania Rating Scale (YMRS)
timeFrame: 12 months
measure: Changes in the Antipsychotic Non-Neurological Side-Effects Rating Scale (ANNSERS)
timeFrame: 12 months
measure: Changes in the Brief Assessment of Cognition in Schizophrenia (BACS)
timeFrame: 12 months
measure: Changes in the Global Assessment of Functioning scale (GAF)
timeFrame: 12 months
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NH Foundation Trust
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter NHS Foundation Trust
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow and Clyde
city: Liverpool
country: United Kingdom
facility: The Walton Centre NHS Foundation Trust
city: London
country: United Kingdom
facility: University College London Hospitals Nhs Foundation Trust
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: Salford Royal NHS Foundation Trust
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust
Study officials:
affiliation: University of Cambridge, UK
name: Alasdair Coles, PhD FRCP
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.