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Efficacy of Maintenance Repetitive Transcranial Magnetic Stimulation (rTMS) in Auditory Verbal Hallucinations (MAINSTIM)

Primary Purpose

Schizophrenia; Psychosis

Status
Not yet recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment
Sham Repetitive Transcranial Magnetic Stimulation (rTMS)
Sponsored by
University Hospital, Caen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Schizophrenia; Psychosis focused on measuring Transcranial Magnetic Stimulation, Auditory verbal Hallucination, Neuronavigation

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male or female; Age ≥ 18 years ≤ 65 years
  • Diagnosis of schizophrenia or schizoaffective disorders according to DSM 5.0 criteria
  • Patients treated with at least one antipsychotic medication
  • Presence of auditory verbal hallucinations despite the optimization of the antipsychotic dosage for at least 6 weeks. This will be operationalized by a minimum AHRS score > 10
  • Stable medication dosage for at least 6 weeks before the rTMS treatment
  • Patient who understands the French language
  • The agreement of the curatorship or tutorship in the case of a protected adult
  • Willing to comply with scheduled visits, as outlined in the protocol
  • Covered by, or having the right to Social Security or European cover
  • Informed and written consent

Exclusion Criteria:

  • Women who are pregnant
  • Patients with contraindications for rTMS (history of epilepsy, neurologic stimulator, pacemaker, cardiac defibrillator, cardiac prosthesis, vascular prosthesis, intracranial clips or clamps, cerebrospinal fluid derivation, metallic splinters in the eyes)
  • Patients included or planning to be included in another medical research protocol
  • Patients unable to complete the protocol follow-up
  • Any brain pathological abnormality known or diagnosed by the cerebral MRI
  • Contre-indication for cerebral MRI (metallic fix tooth prosthesis, neurologic stimulator, pacemaker, cardiac defibrillator, cardiac prosthesis, vascular prosthesis, intracranial clips or clamps, cerebrospinal fluid derivation, metallic splinters in the eyes, severe claustrophobia)

Sites / Locations

  • Caen University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Sham Comparator

Experimental

Arm Label

sham rTMS

active rTMS

Arm Description

The sham treatment, following the group assignment, will be maintained during the two successive phases of the evaluated protocol. One initial sham rTMS phase will consist of four sham stimulation sessions (20 Hz sham) within two consecutive days. One sham rTMS maintenance phase will consist of two sham stimulation sessions on one day every week for one month and then every two weeks for three months. Clinical data will be assessed by an investigator blind to group assignment until the end of the study. Patients will also be blind to stimulation. A questionnaire will assess the investigator physician and patient beliefs about what group the patient was involved in (placebo group or active group) at the end of the treatment initial phase and at the end of the treatment maintenance phase

The active treatment, following the group assignment, will be maintained during the two successive phases of the evaluated protocol. One initial active rTMS phase will consist of four stimulation sessions (20 Hz) within two consecutive days. One active rTMS maintenance phase will consist of two active stimulation sessions on one day every week for one month and then every two weeks for three months.

Outcomes

Primary Outcome Measures

the number of times a patient is assessed as a responder
the number of times a patient is assessed as a responder in the active versus the sham group during their follow-up between baseline (D1) and at the end of the maintenance treatment (M5), i.e. the month after the last maintenance session.

Secondary Outcome Measures

Full Information

First Posted
September 19, 2022
Last Updated
September 30, 2022
Sponsor
University Hospital, Caen
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1. Study Identification

Unique Protocol Identification Number
NCT05550155
Brief Title
Efficacy of Maintenance Repetitive Transcranial Magnetic Stimulation (rTMS) in Auditory Verbal Hallucinations
Acronym
MAINSTIM
Official Title
Efficacy of Maintenance Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment in Reducing Auditory Verbal Hallucinations (AVH) With High Frequency and Neuronavigation Guidance: A Double-blind, Randomized and Multicentric Study
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 3, 2022 (Anticipated)
Primary Completion Date
November 3, 2025 (Anticipated)
Study Completion Date
April 15, 2026 (Anticipated)

3. Sponsor/Collaborators

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

4. Oversight

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

5. Study Description

Brief Summary
Repetitive transcranial magnetic stimulation (rTMS) can alleviate persistent auditory verbal hallucinations (AVH) in schizophrenic patients, but the classical procedure with low-frequency stimulation for several weeks upon the left temporoparietal junction have shown modest therapeutic effects, and there is currently no robust predictive factor to the response of the treatment. In a previous multicentric, randomized, and double-blind controlled study, it has been demonstrated that a high-frequency rTMS over an anatomical target can rapidly affect AVHs. Moreover, an intensification of the classical procedure delivering 20-Hz rTMS over a 2-day period was used in addition to a personalized anatomical stimulation target and neuronavigation guidance. Besides the significant efficacy of the procedure, the efficacy was maximal at two weeks after the end of the treatment. In this project, the hypothesis is that the two-day cure could benefit from maintenance rTMS sessions every week for one month and then every two weeks for 3 months to provide an optimal strategy for a long-lasting AVH reduction. This has for now never been tested. Predictive factors to the response of the treatment are also investigated.
Detailed Description
To investigate the clinical efficacy of a 4-month maintenance procedure of rTMS in AVH reduction, a multicenter, controlled, double-blind study enrolling 120 patients randomly assigned in two groups is proposed. The active group will receive active rTMS with a two-day intense procedure (consisting in 4 20-Hz rTMS sessions within two days) and a maintenance phase with a two- rTMS session every week for one month and then every two weeks the next 3 months (i.e. 24 rTMS sessions). The individual target will be personalized and guided by neuronavigation. The placebo group will benefit from the exact same procedure but with sham rTMS instead of active rTMS. Patients will be carried out during 5 months and what distinguishes responders from non-responders will be studied. Among other variables, BDNF serum levels as a reflect of the individual neural plasticity and the measurement of the scalp-to-cortex distance to the target as a reflect of the cerebral morphological interindividual variations will be investigated.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia; Psychosis
Keywords
Transcranial Magnetic Stimulation, Auditory verbal Hallucination, Neuronavigation

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
sham rTMS
Arm Type
Sham Comparator
Arm Description
The sham treatment, following the group assignment, will be maintained during the two successive phases of the evaluated protocol. One initial sham rTMS phase will consist of four sham stimulation sessions (20 Hz sham) within two consecutive days. One sham rTMS maintenance phase will consist of two sham stimulation sessions on one day every week for one month and then every two weeks for three months. Clinical data will be assessed by an investigator blind to group assignment until the end of the study. Patients will also be blind to stimulation. A questionnaire will assess the investigator physician and patient beliefs about what group the patient was involved in (placebo group or active group) at the end of the treatment initial phase and at the end of the treatment maintenance phase
Arm Title
active rTMS
Arm Type
Experimental
Arm Description
The active treatment, following the group assignment, will be maintained during the two successive phases of the evaluated protocol. One initial active rTMS phase will consist of four stimulation sessions (20 Hz) within two consecutive days. One active rTMS maintenance phase will consist of two active stimulation sessions on one day every week for one month and then every two weeks for three months.
Intervention Type
Device
Intervention Name(s)
Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment
Intervention Description
a 4-month maintenance procedure of active rTMS
Intervention Type
Device
Intervention Name(s)
Sham Repetitive Transcranial Magnetic Stimulation (rTMS)
Intervention Description
a 4-month maintenance procedure of sham rTMS
Primary Outcome Measure Information:
Title
the number of times a patient is assessed as a responder
Description
the number of times a patient is assessed as a responder in the active versus the sham group during their follow-up between baseline (D1) and at the end of the maintenance treatment (M5), i.e. the month after the last maintenance session.
Time Frame
between baseline and month 5

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female; Age ≥ 18 years ≤ 65 years Diagnosis of schizophrenia or schizoaffective disorders according to DSM 5.0 criteria Patients treated with at least one antipsychotic medication Presence of auditory verbal hallucinations despite the optimization of the antipsychotic dosage for at least 6 weeks. This will be operationalized by a minimum AHRS score > 10 Stable medication dosage for at least 6 weeks before the rTMS treatment Patient who understands the French language The agreement of the curatorship or tutorship in the case of a protected adult Willing to comply with scheduled visits, as outlined in the protocol Covered by, or having the right to Social Security or European cover Informed and written consent Exclusion Criteria: Women who are pregnant Patients with contraindications for rTMS (history of epilepsy, neurologic stimulator, pacemaker, cardiac defibrillator, cardiac prosthesis, vascular prosthesis, intracranial clips or clamps, cerebrospinal fluid derivation, metallic splinters in the eyes) Patients included or planning to be included in another medical research protocol Patients unable to complete the protocol follow-up Any brain pathological abnormality known or diagnosed by the cerebral MRI Contre-indication for cerebral MRI (metallic fix tooth prosthesis, neurologic stimulator, pacemaker, cardiac defibrillator, cardiac prosthesis, vascular prosthesis, intracranial clips or clamps, cerebrospinal fluid derivation, metallic splinters in the eyes, severe claustrophobia)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sonia Dollfus, MD-PhD
Phone
02.31.06.50.18
Email
dollfus-s@chu-caen.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sonia Dollfus
Organizational Affiliation
University Caen Normandie
Official's Role
Principal Investigator
Facility Information:
Facility Name
Caen University Hospital
City
Caen
ZIP/Postal Code
14033
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sonia DOLLFUS, MD PhD
Phone
02.31.06.50.18
Email
dollfus-s@chu-caen.fr

12. IPD Sharing Statement

Learn more about this trial

Efficacy of Maintenance Repetitive Transcranial Magnetic Stimulation (rTMS) in Auditory Verbal Hallucinations

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