Evaluation of the Efficacy of Immunomodulatory Therapy in Case of Psychiatric Disorders With Proven Dysimmunity. (TIM-DePisT)
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| ClinicalTrials.gov Identifier: NCT05946486 |
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Recruitment Status :
Not yet recruiting
First Posted : July 14, 2023
Last Update Posted : July 14, 2023
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Sponsor:
University Hospital, Bordeaux
Information provided by (Responsible Party):
University Hospital, Bordeaux
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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).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Mental Disorder | Drug: immunomodulatory treatment by rituximab | Phase 3 |
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
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 174 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Phase III Randomized, Multicenter Open Label Study to Evaluate the Efficacy of Immunomodulatory Therapy in Case of Psychiatric Disorders With Proven Dysimmunity. |
| Estimated Study Start Date : | October 15, 2023 |
| Estimated Primary Completion Date : | January 15, 2026 |
| Estimated Study Completion Date : | December 15, 2026 |
Resource links provided by the National Library of Medicine
Drug Information
available for:
Rituximab
| Arm | Intervention/treatment |
|---|---|
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No Intervention: control group
continuation of ongoing psychiatric care (with or without standard treatment as usual (i.e. antipsychotics, mood stabilisers, antidepressants and/or anxiolytics)).
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Experimental: 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.
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Drug: immunomodulatory treatment by rituximab
1g for adults or 375 mg/m2 for children, renewed at 14 days (+/- 3 days) |
Primary Outcome Measures :
- Adult patients : the remission of psychiatric symptoms at 3 months [ Time Frame: 3 months after randomization ]
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 [ Time Frame: 3 months after randomization ]
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 [ Time Frame: 12 months after randomization ]
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 [ Time Frame: 6 months after randomization ]
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 [ Time Frame: 1 month after randomization ]
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 [ Time Frame: 12 months after randomization ]
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 [ Time Frame: 6 months after randomization ]
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 [ Time Frame: 1 month after randomization ]
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 [ Time Frame: 1 month after randomization ]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 [ Time Frame: 3 months after randomization ]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 [ Time Frame: 6 months after randomization ]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 [ Time Frame: 12 months after randomization ]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 [ Time Frame: 1 month after randomization ]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 [ Time Frame: 3 months after randomization ]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 [ Time Frame: 6 months after randomization ]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 [ Time Frame: 12 months after randomization ]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.
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| Ages Eligible for Study: | 6 Years and older (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05946486
Contacts
| Contact: Frédéric VILLEGA, MD, PhD | +33 (0)5 56 79 56 41 | frederic.villega@chu-bordeaux.fr | |
| Contact: Aurore Capelli, PhD | 0557820877 | aurore.capelli@chu-bordeaux.fr |
Locations
| France | |
| Centre Hospitalier Charles Perrens | |
| Bordeaux, France | |
| Contact: Bruno Aouizerate | |
| Sub-Investigator: Anouck Amestoy | |
| CHU de Bordeaux | |
| Bordeaux, France | |
| Contact: Frédéric Villega | |
| Sub-Investigator: Valérie Adrian | |
| Centre hospitalier le Vinatier | |
| Bron, France | |
| Contact: Romain Rey | |
| CHU de Clermond Ferrand | |
| Clermont-Ferrand, France | |
| Contact: Pierre-Michel Llorca | |
| APHP Louis Mourier | |
| Colombes, France | |
| Contact: Catherine Dubertet | |
| APHP Henri Mondor | |
| Créteil, France | |
| Contact: Marion Leboyer | |
| APHP Kremlin Bicetre | |
| Le Kremlin-Bicêtre, France | |
| Contact: Kumaran Deiva | |
| CHU de Montpellier | |
| Montpellier, France | |
| Contact: Delphine Capdevielle | |
| CHU de Strasbourg | |
| Strasbourg, France | |
| Contact: Fabrice Berna | |
Sponsors and Collaborators
University Hospital, Bordeaux
Investigators
| Principal Investigator: | Frédéric VILLEGA, MD, PhD | University Hospital, Bordeaux |
| Responsible Party: | University Hospital, Bordeaux |
| ClinicalTrials.gov Identifier: | NCT05946486 |
| Other Study ID Numbers: |
CHUBX 2019/59 |
| First Posted: | July 14, 2023 Key Record Dates |
| Last Update Posted: | July 14, 2023 |
| Last Verified: | July 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by University Hospital, Bordeaux:
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psychotic disorders pathogenic central nervous system (CNS) autoantibodies immunomodulatory therapy |
Additional relevant MeSH terms:
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Mental Disorders Problem Behavior Behavioral Symptoms Rituximab Antineoplastic Agents, Immunological |
Antineoplastic Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents |