Evaluation of the Efficacy of Immunomodulatory Therapy in Case of Psychiatric Disorders With Proven Dysimmunity.

NCT ID: NCT05946486

Last Updated: 2023-07-14

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 174 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-15
• Study Completion Date: 2026-12-15

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

Conditions

Mental Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

control group

continuation of ongoing psychiatric care (with or without standard treatment as usual (i.e. antipsychotics, mood stabilisers, antidepressants and/or anxiolytics)).

Group Type: NO_INTERVENTION

No interventions assigned to this group

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.

Group Type: EXPERIMENTAL

immunomodulatory treatment by rituximab

Intervention Type: DRUG

1g for adults or 375 mg/m2 for children, renewed at 14 days (+/- 3 days)

Interventions

immunomodulatory treatment by rituximab

1g for adults or 375 mg/m2 for children, renewed at 14 days (+/- 3 days)

Intervention Type: DRUG

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 2.
• 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
• Pregnant or breastfeeding women
• Currently receiving an investigational drug or received an investigational drug or device within 30 days (or 5 half-lives for drugs, whichever is longer) prior to screening.
• Previous treatment with rituximab in the past 12 months.
• Patients with a history of recurring or chronic infections or with underlying conditions which may further predispose them to serious infection (e.g. hypogammaglobulinemia).
• Recent vaccination with live viral vaccine (within 3 months).
• Any other medical illness or disability that, in the opinion of the investigator, would compromise effective trial participation.

• Minimum Eligible Age: 6 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Bordeaux

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Frédéric VILLEGA, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Bordeaux

Locations

Centre Hospitalier Charles Perrens

Bordeaux, , France

CHU de Bordeaux

Bordeaux, , France

Centre hospitalier le Vinatier

Bron, , France

CHU de Clermond Ferrand

Clermont-Ferrand, , France

APHP Louis Mourier

Colombes, , France

APHP Henri Mondor

Créteil, , France

APHP Kremlin Bicetre

Le Kremlin-Bicêtre, , France

CHU de Montpellier

Montpellier, , France

CHU de Strasbourg

Strasbourg, , France

Countries

France

Central Contacts

Frédéric VILLEGA, MD, PhD

Role: CONTACT

frederic.villega@chu-bordeaux.fr

+33 (0)5 56 79 56 41

Aurore Capelli, PhD

Role: CONTACT

aurore.capelli@chu-bordeaux.fr

0557820877

Facility Contacts

Bruno Aouizerate

Role: primary

Frédéric Villega

Role: primary

Romain Rey

Role: primary

Pierre-Michel Llorca

Role: primary

Catherine Dubertet

Role: primary

Marion Leboyer

Role: primary

Kumaran Deiva

Role: primary

Delphine Capdevielle

Role: primary

Fabrice Berna

Role: primary

Other Identifiers

CHUBX 2019/59

Identifier Type: -

Identifier Source: org_study_id