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

Mental Disorder Clinical Trial

— TIM-DePisT  

Official title:

Phase III Randomized, Multicenter Open Label Study to Evaluate the Efficacy of Immunomodulatory Therapy in Case of Psychiatric Disorders With Proven Dysimmunity.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05946486
• Other study ID #: CHUBX 2019/59
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: October 15, 2023
• Est. completion date: December 15, 2026

Study information

• Verified date: July 2023
• Source: University Hospital, Bordeaux
• Contact: Frédéric VILLEGA, MD, PhD
• Phone: +33 (0)5 56 79 56 41
• Email: frederic.villega[@]chu-bordeaux.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 174
• Est. completion date: December 15, 2026
• Est. primary completion date: January 15, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Mental Disorder
• Mental Disorders
• Problem Behavior

Intervention

Drug:
• immunomodulatory treatment by rituximab
1g for adults or 375 mg/m2 for children, renewed at 14 days (+/- 3 days)

Locations

Country	Name	City	State
France	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

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Bordeaux

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Adult Patients : the remission of psychiatric symptoms at 12 months	the remission of psychiatric symptoms defined as: - For adult patients: 20% decrease from baseline of Brief psychiatric rating scale-Extended (BPRS-E scale).	12 months after randomization
Secondary	Adult Patients : the remission of psychiatric symptoms at 6 months	the remission of psychiatric symptoms defined as: - For adult patients: 20% decrease from baseline of Brief psychiatric rating scale-Extended (BPRS-E scale).	6 months after randomization
Secondary	Adult Patients : the remission of psychiatric symptoms at 1 month	the remission of psychiatric symptoms defined as: - For adult patients: 20% decrease from baseline of Brief psychiatric rating scale-Extended (BPRS-E scale).	1 month after randomization
Secondary	Minor patients : the remission of psychiatric symptoms at 12 months	The primary endpoint outcome is the remission of psychiatric symptoms at 12 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.	12 months after randomization
Secondary	Minor patients : the remission of psychiatric symptoms at 6 months	The primary endpoint outcome is the remission of psychiatric symptoms, 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.	6 months after randomization
Secondary	Minor patients : the remission of psychiatric symptoms at 1 month	The primary endpoint outcome is the remission of psychiatric symptoms, 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.	1 month after randomization
Secondary	Adult patients : general functioning at 1 month	for Global assessment of functioning scale (GAF scale), a mean score of 60 and above is expected to be achieved indicating patients experiencing mild to moderate symptoms and functioning pretty well in daily life.	1 month after randomization
Secondary	Adult patients : general functioning at 3 months	for Global assessment of functioning scale (GAF scale), a mean score of 60 and above is expected to be achieved indicating patients experiencing mild to moderate symptoms and functioning pretty well in daily life.	3 months after randomization
Secondary	Adult patients : general functioning at 6 months	for Global assessment of functioning scale (GAF scale), a mean score of 60 and above is expected to be achieved indicating patients experiencing mild to moderate symptoms and functioning pretty well in daily life.	6 months after randomization
Secondary	Adult patients : general functioning at 12 months	for Global assessment of functioning scale (GAF scale), a mean score of 60 and above is expected to be achieved indicating patients experiencing mild to moderate symptoms and functioning pretty well in daily life.	12 months after randomization
Secondary	Minor patients : Child behaviour check list (CBCL) /6-18 scale at 1 month	For children>6 years old with an acute first episode or relapse of psychotic disorders: clinically significant difference =3 from baseline of CBCL/6-18 (Child Behavior Checklist) scale.	1 month after randomization
Secondary	Minor patients : Child behaviour check list (CBCL) /6-18 scale at 3 months	For children>6 years old with an acute first episode or relapse of psychotic disorders: clinically significant difference =3 from baseline of CBCL/6-18 (Child Behavior Checklist) scale.	3 months after randomization
Secondary	Minor patients : Child behaviour check list (CBCL) /6-18 scale at 6 months	For children>6 years old with an acute first episode or relapse of psychotic disorders: clinically significant difference =3 from baseline of CBCL/6-18 (Child Behavior Checklist) scale.	6 months after randomization
Secondary	Minor patients : Child behaviour check list (CBCL) /6-18 scale at 12 months	For children>6 years old with an acute first episode or relapse of psychotic disorders: clinically significant difference =3 from baseline of CBCL/6-18 (Child Behavior Checklist) scale.	12 months after randomization