Clinical trial NCT05946486: Evaluation of the Efficacy of Immunomodulatory Therapy in Case of Psychiatric Disorders With Proven Dysimmunity.
Official title: Phase III Randomized, Multicenter Open Label Study to Evaluate the Efficacy of Immunomodulatory Therapy in Case of Psychiatric Disorders With Proven Dysimmunity.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Mental Disorder
Keywords: psychotic disorders
pathogenic central nervous system (CNS) autoantibodies
immunomodulatory therapy
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2023-07-14
Enrollment: 174
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: Adult patients : the remission of psychiatric symptoms at 3 months
timeFrame: 3 months after randomization
measure: Minor patients : the remission of psychiatric symptoms at 3 months
timeFrame: 3 months after randomization
Secondary outcomes:
measure: Adult Patients : the remission of psychiatric symptoms at 12 months
timeFrame: 12 months after randomization
measure: Adult Patients : the remission of psychiatric symptoms at 6 months
timeFrame: 6 months after randomization
measure: Adult Patients : the remission of psychiatric symptoms at 1 month
timeFrame: 1 month after randomization
measure: Minor patients : the remission of psychiatric symptoms at 12 months
timeFrame: 12 months after randomization
measure: Minor patients : the remission of psychiatric symptoms at 6 months
timeFrame: 6 months after randomization
measure: Minor patients : the remission of psychiatric symptoms at 1 month
timeFrame: 1 month after randomization
measure: Adult patients : general functioning at 1 month
timeFrame: 1 month after randomization
measure: Adult patients : general functioning at 3 months
timeFrame: 3 months after randomization
measure: Adult patients : general functioning at 6 months
timeFrame: 6 months after randomization
measure: Adult patients : general functioning at 12 months
timeFrame: 12 months after randomization
measure: Minor patients : Child behaviour check list (CBCL) /6-18 scale at 1 month
timeFrame: 1 month after randomization
measure: Minor patients : Child behaviour check list (CBCL) /6-18 scale at 3 months
timeFrame: 3 months after randomization
measure: Minor patients : Child behaviour check list (CBCL) /6-18 scale at 6 months
timeFrame: 6 months after randomization
measure: Minor patients : Child behaviour check list (CBCL) /6-18 scale at 12 months
timeFrame: 12 months after randomization
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Centre Hospitalier Charles Perrens
city: Bordeaux
country: France
facility: CHU de Bordeaux
city: Bron
country: France
facility: Centre hospitalier le Vinatier
city: Clermont-Ferrand
country: France
facility: CHU de Clermond Ferrand
city: Colombes
country: France
facility: APHP Louis Mourier
city: Créteil
country: France
facility: APHP Henri Mondor
city: Le Kremlin-Bicêtre
country: France
facility: APHP Kremlin Bicetre
city: Montpellier
country: France
facility: CHU de Montpellier
city: Strasbourg
country: France
facility: CHU de Strasbourg
Study officials:
affiliation: University Hospital, Bordeaux
name: Frédéric VILLEGA, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: