IVIG and Rituximab in Antibody-associated Psychosis - SINAPPS2

Conditions

Autoimmune Encephalitis, Psychosis

Keywords

Psychosis, Immunotherapy, Autoantibodies

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.

Soon‐Tae Lee, Hesham Abboud, Sarosh R. Irani, Hideto Nakajima, Amanda L. Piquet et al. (15 authors)

Frontiers in Neurology2024-08-1314 citations

10.3389/fneur.2024.1437913

Generate-Boost: study protocol for a prospective, multicenter, randomized controlled, double-blinded phase II trial to evaluate efficacy and safety of bortezomib in patients with severe autoimmune encephalitis.

Wickel J, Chung HY, Platzer S, Lehmann T, Prüss H, Leypoldt F, Günther A, Scherag A, Geis C, GENERATE Study Group.

2020-07-0836 citations

10.1186/s13063-020-04516-7

Intravenous immunoglobulin and rituximab versus placebo treatment of antibody-associated psychosis: study protocol of a randomised phase IIa double-blinded placebo-controlled trial (SINAPPS2).

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.

2019-06-079 citations

10.1186/s13063-019-3336-1

Interventions

DRUGIntravenous immunoglobulin

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

DRUGPlacebo

This is the control, or sham, treatment

DRUGRituximab

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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

16 Years to 70 Years

Healthy volunteers

No

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

Design outcomes

Primary

Measure	Time frame	Description
Time to start of symptomatic recovery (symptomatic remission sustained for at least 6 months)	up to 18 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

Secondary

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

Countries

United Kingdom

Contacts

PRINCIPAL_INVESTIGATORAlasdair Coles, PhD FRCP

University of Cambridge, UK

Outcome results

None listed