ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
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

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.


Condition or disease Intervention/treatment Phase
Psychosis Autoimmune Encephalitis Drug: Intravenous immunoglobulin Drug: Placebo Drug: Rituximab Phase 2

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomised Phase II Double-blinded Placebo-controlled Trial of Intravenous Immunoglobulins and Rituximab in Patients With Antibody-associated Psychosis (SINAPPS2)
Actual Study Start Date : November 1, 2017
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2021


Arm Intervention/treatment
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.
Drug: Intravenous immunoglobulin
This is a blood product containing antibodies from thousands of healthy donors.
Other Names:
  • IVIG
  • Intratect

Drug: Rituximab
Rituximab is a type of biological therapy. It removes B-cells and helps to reduce the inflammation
Other Name: MabThera

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.
Drug: Placebo
This is the control, or sham, treatment
Other Name: Saline solution




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. Number of adverse effects [ Time Frame: 18 months ]
    total number of patient reported adverse effects

  4. 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)

  5. 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)

  6. 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)

  7. 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

  8. Changes in the Young Mania Rating Scale (YMRS) [ Time Frame: 12 months ]
    Change in YMRS total score from baseline to month 12

  9. 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

  10. Changes in the Brief Assessment of Cognition in Schizophrenia (BACS) [ Time Frame: 12 months ]
    Change in BACS scores from baseline to month 12

  11. Changes in the Global Assessment of Functioning scale (GAF) [ Time Frame: 12 months ]
    Change in the GAF score from baseline to month 12



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03194815


Contacts
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

Locations
United Kingdom
Cambridge University Hospitals Recruiting
Cambridge, United Kingdom
Contact: Alasdair Coles, PhD FRCP    +44 (0)1223 762016    ajc1020@medschl.cam.ac.uk   
University College London Hospitals Nhs Foundation Trust Recruiting
London, United Kingdom, NW1 2PG
Contact: Michael Zandi, PhD MRCP       m.zandi@ucl.ac.uk   
Oxford Radcliffe Hospitals Recruiting
Oxford, United Kingdom
Contact: Belinda Lennox, DM MRCPsych    : +44(0)1865 613145    belinda.lennox@psych.ox.ac.uk   
Sponsors and Collaborators
University of Cambridge
University of Oxford
Investigators
Principal Investigator: Alasdair Coles, PhD FRCP University of Cambridge, UK

Additional Information:
Responsible Party: Alasdair Coles, Revd. Prof. Alasdair Coles, Chief Investigator, University of Cambridge
ClinicalTrials.gov Identifier: NCT03194815     History of Changes
Other Study ID Numbers: SINAPPS 2
First Posted: June 21, 2017    Key Record Dates
Last Update Posted: February 19, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Alasdair Coles, University of Cambridge:
Psychosis
Immunotherapy
Autoantibodies

Additional relevant MeSH terms:
Psychotic Disorders
Mental Disorders
Schizophrenia Spectrum and Other Psychotic Disorders
Encephalitis
Hashimoto Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Thyroiditis, Autoimmune
Thyroiditis
Thyroid Diseases
Endocrine System Diseases
Antibodies
Rituximab
Immunoglobulins
Immunoglobulins, Intravenous
gamma-Globulins
Rho(D) Immune Globulin
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Antirheumatic Agents