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IVIG and Rituximab in Antibody-associated Psychosis - SINAPPS2 (SINAPPS2)

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ClinicalTrials.gov Identifier: NCT03194815
Recruitment Status : Recruiting
First Posted : June 21, 2017
Last Update Posted : February 19, 2018
Sponsor:
Collaborator:
University of Oxford
Information provided by (Responsible Party):
Alasdair Coles, University of Cambridge

Tracking Information
First Submitted Date  ICMJE February 2, 2017
First Posted Date  ICMJE June 21, 2017
Last Update Posted Date February 19, 2018
Actual Study Start Date  ICMJE November 1, 2017
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 19, 2017)
Time to start of remission [ Time Frame: 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 19, 2017)
  • Time to first treatment response (whether sustained or not) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 18 months ]
    total number of patient reported adverse effects
  • Proportion of patients reaching 20% reduction in PANSS total score [ Time Frame: 12 months ]
    20% reduction in the PANSS total score (all PANNS items included)
  • Proportion of patients reaching 30% reduction in PANSS total score [ Time Frame: 12 months ]
    30% reduction in the PANSS total score (all PANNS items included)
  • Proportion of patients reaching 40% reduction in PANSS total score [ Time Frame: 12 months ]
    40% reduction in the PANSS total score (all PANNS items included)
  • Changes in the Clinical Global Impression Scale in Schizophrenia (CGI-Schizophrenia) [ Time Frame: 12 months ]
    Change in CGI-Schizophrenia scores from baseline to month 12
  • Changes in the Young Mania Rating Scale (YMRS) [ Time Frame: 12 months ]
    Change in YMRS total score from baseline to month 12
  • Changes in the Antipsychotic Non-Neurological Side-Effects Rating Scale (ANNSERS) [ Time Frame: 12 months ]
    Change in ANNSERS total score from baseline to month 12
  • Changes in the Brief Assessment of Cognition in Schizophrenia (BACS) [ Time Frame: 12 months ]
    Change in BACS scores from baseline to month 12
  • Changes in the Global Assessment of Functioning scale (GAF) [ Time Frame: 12 months ]
    Change in the GAF score from baseline to month 12
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE IVIG and Rituximab in Antibody-associated Psychosis - SINAPPS2
Official Title  ICMJE A Randomised Phase II Double-blinded Placebo-controlled Trial of Intravenous Immunoglobulins and Rituximab in Patients With Antibody-associated Psychosis (SINAPPS2)
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Psychosis
  • Autoimmune Encephalitis
Intervention  ICMJE
  • Drug: Intravenous immunoglobulin
    This is a blood product containing antibodies from thousands of healthy donors.
    Other Names:
    • IVIG
    • Intratect
  • Drug: Placebo
    This is the control, or sham, treatment
    Other Name: Saline solution
  • Drug: Rituximab
    Rituximab is a type of biological therapy. It removes B-cells and helps to reduce the inflammation
    Other Name: MabThera
Study Arms  ICMJE
  • Active Comparator: 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.
    Interventions:
    • Drug: Intravenous immunoglobulin
    • Drug: Rituximab
  • Placebo Comparator: 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.
    Intervention: Drug: Placebo
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 19, 2017)
80
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Acute psychosis >2 weeks, either first episode or relapse after remission (remission defined as PANSS≤3 on PANSS items P1, G9, P3, P2, G5, N1, N4, N6 for previous 6 months)
  • Serum or CSF neuronal membrane autoantibodies at pathological levels (including NMDAR, LGI1 and other)
  • PANSS ≥4 on P1, G9, P3, P2, G5, N1, N4, N6.

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Alastdair Coles, PhD FRCP +44 (0)1223 762016 ajc1020@medschl.cam.ac.uk
Contact: Belinda Lennox, DM MRCPsych : +44(0)1865 613145 belinda.lennox@psych.ox.ac.uk
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03194815
Other Study ID Numbers  ICMJE SINAPPS 2
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Alasdair Coles, University of Cambridge
Study Sponsor  ICMJE University of Cambridge
Collaborators  ICMJE University of Oxford
Investigators  ICMJE
Principal Investigator: Alasdair Coles, PhD FRCP University of Cambridge, UK
PRS Account University of Cambridge
Verification Date February 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP