Phase III Randomized, Multicenter Open Label Study to Evaluate the Efficacy of Immunomodulatory Therapy in Case of Psychiatric Disorders With Proven Dysimmunity.
Overview
- Phase
- Phase 3
- Intervention
- immunomodulatory treatment by rituximab
- Conditions
- Mental Disorder
- Sponsor
- University Hospital, Bordeaux
- Enrollment
- 174
- Locations
- 9
- Primary Endpoint
- Minor patients : the remission of psychiatric symptoms at 3 months
- Status
- Not yet recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This is an open phase III randomized clinical trial studying the superiority of management by immunomodulator treatment of psychiatric disorders (psychosis and bipolar disorders) for patients previously identified as carriers of autoimmunity such as as the presence of a pathogenic anti-glutamatergic NMDA receptor antibody (NMDAr-Ac).
Detailed Description
This is an open phase III randomized clinical trial studying the superiority of management by immunomodulator treatment of psychiatric disorders (psychosis and bipolar disorders) for patients previously identified as carriers of autoimmunity such as as the presence of a pathogenic anti-glutamatergic NMDA receptor antibody (NMDAr-Ac). The aim is to assess the clinical efficacy of this treatment associated with the usual recommended psychotropic treatment. To meet this objective, we will use, via a National Center for Scientific Research (CNRS) Research laboratory in Bordeaux, a very sensitive diagnostic platform to detect and demonstrate the pathogenesis of antibodies in patient serum. This platform is operational only within the framework of validation of the results by the reference center for neurological autoimmune diseases in Lyon
Investigators
Eligibility Criteria
Inclusion Criteria
- •For Adult: First acute or relapse of psychotic disorders defined by the BPRS-E scale with or without standard pharmacological treatment.
- •For Children: Child over 6 years old with a first acute or relapse of psychotic disorders defined by the Kiddie sads-PL scale with or without standard pharmacological treatment.
- •Biological diagnosis of pathogenic CNS autoantibodies in the blood.
- •MDC scale score \>3 is required for inclusion in step
- •Normal ECG in case of previous heart disease.
- •Informed consent of the patient or his legal representatives.
- •Effective contraception for women of childbearing potential during the study and for at least 12 months after the last rituximab administration.
Exclusion Criteria
- •Developmental disorder related to a genetic disease.
- •Co-existing disorder of severe neurological disease.
- •Chronic psychotic disorders receiving ongoing neuroleptic treatment with efficacy.
- •Hypersensitivity to the active substance (rituximab) or to murine proteins, or to any of the other excipients
- •Blood platelets \< 75x109/L
- •Neutrophils \< 1.5x109/L
- •Neoplastic pathology,
- •Hepatitis B or HIV infection,
- •Contraindication to immunosuppressant treatment (active severe infection, severely immunocompromised state).
- •Severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease
Arms & Interventions
experimental group
immunomodulatory treatment by rituximab, 1g for adults or 375 mg/m2 for children, renewed at 14 days (+/- 3 days), added to stable ongoing psychiatric care (with or without standard treatment as usual ( i.e. antipsychotic, mood stabiliser, antidepressant and/or anxiolytic)). The rituximab is the best immunomodulatory treatment recommended for neurologic encephalitis.
Intervention: immunomodulatory treatment by rituximab
Outcomes
Primary Outcomes
Minor patients : the remission of psychiatric symptoms at 3 months
Time Frame: 3 months after randomization
The primary endpoint outcome is the remission of psychiatric symptoms at 3 months, defined as: - For patients \<18years or adults patients included at adolescent age at 2nd step inclusion visit: clinically significant difference ≤3 from baseline of CBCL/6-18 (Child Behavior Checklist) scale.
Adult patients : the remission of psychiatric symptoms at 3 months
Time Frame: 3 months after randomization
The primary endpoint outcome is the remission of psychiatric symptoms at 3 months, defined as: - For adult patients: 20% decrease from baseline of Brief psychiatric rating scale-Extended (BPRS-E scale).
Secondary Outcomes
- Adult Patients : the remission of psychiatric symptoms at 12 months(12 months after randomization)
- Adult Patients : the remission of psychiatric symptoms at 6 months(6 months after randomization)
- Minor patients : the remission of psychiatric symptoms at 1 month(1 month after randomization)
- Minor patients : Child behaviour check list (CBCL) /6-18 scale at 1 month(1 month after randomization)
- Minor patients : the remission of psychiatric symptoms at 12 months(12 months after randomization)
- Adult patients : general functioning at 1 month(1 month after randomization)
- Adult patients : general functioning at 12 months(12 months after randomization)
- Minor patients : Child behaviour check list (CBCL) /6-18 scale at 12 months(12 months after randomization)
- Adult patients : general functioning at 6 months(6 months after randomization)
- Minor patients : Child behaviour check list (CBCL) /6-18 scale at 3 months(3 months after randomization)
- Adult Patients : the remission of psychiatric symptoms at 1 month(1 month after randomization)
- Minor patients : the remission of psychiatric symptoms at 6 months(6 months after randomization)
- Adult patients : general functioning at 3 months(3 months after randomization)
- Minor patients : Child behaviour check list (CBCL) /6-18 scale at 6 months(6 months after randomization)