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

NCT05946486 | Not Yet Recruiting Phase 3

• 1 other identifier: CHUBX 2019/59
• Study Type: interventional
• Target: 174
• Locations: 1 country
• Sites: 9

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).

Conditions

Mental Disorder

Keywords

psychotic disorders; pathogenic central nervous system (CNS) autoantibodies; immunomodulatory therapy

Outcome Measures

Primary Outcomes (2)

• Adult patients : the remission of psychiatric symptoms at 3 months

  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).

  3 months after randomization

• Minor patients : the remission of psychiatric symptoms at 3 months

  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.

  3 months after randomization

Secondary Outcomes (14)

• 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

• Adult Patients : the remission of psychiatric symptoms at 1 month

  1 month after randomization

• Minor patients : the remission of psychiatric symptoms at 12 months

  12 months after randomization

• Minor patients : the remission of psychiatric symptoms at 6 months

  6 months after randomization

Study Arms (2)

control group

NO INTERVENTION

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

experimental group

EXPERIMENTAL

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.

Drug: immunomodulatory treatment by rituximab

Interventions

immunomodulatory treatment by rituximab DRUG

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

experimental group

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• University Hospital, Bordeaux: lead

Study Sites (9)

Centre Hospitalier Charles Perrens

Bordeaux, France

Location

CHU de Bordeaux

Bordeaux, France

Location

Centre hospitalier le Vinatier

Bron, France

Location

CHU de Clermond Ferrand

Clermont-Ferrand, France

Location

APHP Louis Mourier

Colombes, France

Location

APHP Henri Mondor

Créteil, France

Location

APHP Kremlin Bicetre

Le Kremlin-Bicêtre, France

Location

CHU de Montpellier

Montpellier, France

Location

CHU de Strasbourg

Strasbourg, France

Location

MeSH Terms

Conditions

Mental Disorders; Psychotic Disorders

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders

Study Officials

• Frédéric VILLEGA, MD, PhD

  University Hospital, Bordeaux

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Frédéric VILLEGA, MD, PhD

CONTACT

+33 (0)5 56 79 56 41; frederic.villega@chu-bordeaux.fr

Aurore Capelli, PhD

CONTACT

0557820877; aurore.capelli@chu-bordeaux.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2023
• First Posted: July 14, 2023
• Study Start: October 15, 2023
• Primary Completion: January 15, 2026
• Study Completion (Estimated): December 15, 2026
• Last Updated: July 14, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (9)