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Evaluation of the Efficacy of Immunomodulatory Therapy in Case of Psychiatric Disorders With Proven Dysimmunity. (TIM-DePisT)

Primary Purpose

Mental Disorder

Status
Not yet recruiting
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
immunomodulatory treatment by rituximab
Sponsored by
University Hospital, Bordeaux
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mental Disorder focused on measuring psychotic disorders, pathogenic central nervous system (CNS) autoantibodies, immunomodulatory therapy

Eligibility Criteria

6 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Centre Hospitalier Charles Perrens
  • CHU de Bordeaux
  • Centre hospitalier le Vinatier
  • CHU de Clermond Ferrand
  • APHP Louis Mourier
  • APHP Henri Mondor
  • APHP Kremlin Bicetre
  • CHU de Montpellier
  • CHU de Strasbourg

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

control group

experimental group

Arm Description

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

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.

Outcomes

Primary Outcome Measures

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).
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.

Secondary Outcome Measures

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).
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).
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
July 7, 2023
Last Updated
July 7, 2023
Sponsor
University Hospital, Bordeaux
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1. Study Identification

Unique Protocol Identification Number
NCT05946486
Brief Title
Evaluation of the Efficacy of Immunomodulatory Therapy in Case of Psychiatric Disorders With Proven Dysimmunity.
Acronym
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.
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 15, 2023 (Anticipated)
Primary Completion Date
January 15, 2026 (Anticipated)
Study Completion Date
December 15, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Bordeaux

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mental Disorder
Keywords
psychotic disorders, pathogenic central nervous system (CNS) autoantibodies, immunomodulatory therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
174 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
control group
Arm Type
No Intervention
Arm Description
continuation of ongoing psychiatric care (with or without standard treatment as usual (i.e. antipsychotics, mood stabilisers, antidepressants and/or anxiolytics)).
Arm Title
experimental group
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
immunomodulatory treatment by rituximab
Intervention Description
1g for adults or 375 mg/m2 for children, renewed at 14 days (+/- 3 days)
Primary Outcome Measure Information:
Title
Adult patients : the remission of psychiatric symptoms at 3 months
Description
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).
Time Frame
3 months after randomization
Title
Minor patients : the remission of psychiatric symptoms at 3 months
Description
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.
Time Frame
3 months after randomization
Secondary Outcome Measure Information:
Title
Adult Patients : the remission of psychiatric symptoms at 12 months
Description
the remission of psychiatric symptoms defined as: - For adult patients: 20% decrease from baseline of Brief psychiatric rating scale-Extended (BPRS-E scale).
Time Frame
12 months after randomization
Title
Adult Patients : the remission of psychiatric symptoms at 6 months
Description
the remission of psychiatric symptoms defined as: - For adult patients: 20% decrease from baseline of Brief psychiatric rating scale-Extended (BPRS-E scale).
Time Frame
6 months after randomization
Title
Adult Patients : the remission of psychiatric symptoms at 1 month
Description
the remission of psychiatric symptoms defined as: - For adult patients: 20% decrease from baseline of Brief psychiatric rating scale-Extended (BPRS-E scale).
Time Frame
1 month after randomization
Title
Minor patients : the remission of psychiatric symptoms at 12 months
Description
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.
Time Frame
12 months after randomization
Title
Minor patients : the remission of psychiatric symptoms at 6 months
Description
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.
Time Frame
6 months after randomization
Title
Minor patients : the remission of psychiatric symptoms at 1 month
Description
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.
Time Frame
1 month after randomization
Title
Adult patients : general functioning at 1 month
Description
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.
Time Frame
1 month after randomization
Title
Adult patients : general functioning at 3 months
Description
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.
Time Frame
3 months after randomization
Title
Adult patients : general functioning at 6 months
Description
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.
Time Frame
6 months after randomization
Title
Adult patients : general functioning at 12 months
Description
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.
Time Frame
12 months after randomization
Title
Minor patients : Child behaviour check list (CBCL) /6-18 scale at 1 month
Description
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.
Time Frame
1 month after randomization
Title
Minor patients : Child behaviour check list (CBCL) /6-18 scale at 3 months
Description
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.
Time Frame
3 months after randomization
Title
Minor patients : Child behaviour check list (CBCL) /6-18 scale at 6 months
Description
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.
Time Frame
6 months after randomization
Title
Minor patients : Child behaviour check list (CBCL) /6-18 scale at 12 months
Description
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.
Time Frame
12 months after randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Frédéric VILLEGA, MD, PhD
Phone
+33 (0)5 56 79 56 41
Email
frederic.villega@chu-bordeaux.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Aurore Capelli, PhD
Phone
0557820877
Email
aurore.capelli@chu-bordeaux.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frédéric VILLEGA, MD, PhD
Organizational Affiliation
University Hospital, Bordeaux
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre Hospitalier Charles Perrens
City
Bordeaux
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bruno Aouizerate
First Name & Middle Initial & Last Name & Degree
Anouck Amestoy
Facility Name
CHU de Bordeaux
City
Bordeaux
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Frédéric Villega
First Name & Middle Initial & Last Name & Degree
Valérie Adrian
Facility Name
Centre hospitalier le Vinatier
City
Bron
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Romain Rey
Facility Name
CHU de Clermond Ferrand
City
Clermont-Ferrand
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pierre-Michel Llorca
Facility Name
APHP Louis Mourier
City
Colombes
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Catherine Dubertet
Facility Name
APHP Henri Mondor
City
Créteil
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marion Leboyer
Facility Name
APHP Kremlin Bicetre
City
Le Kremlin-Bicêtre
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kumaran Deiva
Facility Name
CHU de Montpellier
City
Montpellier
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Delphine Capdevielle
Facility Name
CHU de Strasbourg
City
Strasbourg
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fabrice Berna

12. IPD Sharing Statement

Plan to Share IPD
No

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

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