Schizophrenia; PsychosisMAINSTIMNCT05550155
Efficacy of Maintenance Repetitive Transcranial Magnetic Stimulation (rTMS) in Auditory Verbal Hallucinations
A study testing Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment in people with Schizophrenia; Psychosis, run by University Hospital, Caen at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizophrenia; Psychosis
- What is being tested?
- Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteFrance
- Study dates
- 30 Oct 2023to 30 Nov 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Caen University Hospital
Caen, 14033
Sonia DOLLFUS, MD PhD
02.31.06.50.18, dollfus-s@chu-caen.fr
About this study
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
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.
Read the 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.
- Conditions
- Schizophrenia; Psychosis
- Being tested
- Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment, Sham Repetitive Transcranial Magnetic Stimulation (rTMS)
- Keywords
- Transcranial Magnetic Stimulation, Auditory verbal Hallucination, Neuronavigation
- Medical subject headings
- Schizophrenia, Psychotic Disorders, Hallucinations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Repetitive Transcranial Magnetic Stimulation (rTMS) TreatmentDevice
a 4-month maintenance procedure of active rTMS
Sham Repetitive Transcranial Magnetic Stimulation (rTMS)Device
a 4-month maintenance procedure of sham rTMS
| Study group | Role | What they receive |
|---|---|---|
| sham rTMS | Sham comparator | 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 Receives: Device: Sham Repetitive Transcranial Magnetic Stimulation (rTMS) |
| active rTMS | Experimental | 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. Receives: Device: Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: between baseline and month 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2022
- Study start30 Oct 2023
- Primary completion30 Dec 2026 (estimated)
- Study completion30 Nov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Schizophrenia; PsychosisStudies of the same condition, open and under way.
- More trials run by University Hospital, CaenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Caen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sonia Dollfus, Principal investigator, University Caen Normandie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05550155
- Sponsor's protocol ID
- 21-0157
- Acronym
- MAINSTIM
- Status last verified
- Jul 2025
- First submitted
- 19 Sep 2022
- Last updated
- 25 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05550155
- Acronym / sponsor ID
- MAINSTIM / 21-0157
- Conditions
- Schizophrenia; Psychosis
- Keywords
- Transcranial Magnetic Stimulation, Auditory verbal Hallucination, Neuronavigation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- University Hospital, CaenUniversity, hospital or other
- Study start
- 30 Oct 2023 (actual)
- Primary completion
- 30 Dec 2026 (estimated)
- Study completion
- 30 Nov 2027 (estimated)
- First posted
- 22 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| sham rTMS | Sham comparator | Device: Sham Repetitive Transcranial Magnetic Stimulation (rTMS)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 |
| active rTMS | Experimental | Device: Repetitive Transcranial Magnetic Stimulation (rTMS) TreatmentThe 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Repetitive Transcranial Magnetic Stimulation (rTMS) Treatmenta 4-month maintenance procedure of active rTMS | Device | active rTMS |
| Sham Repetitive Transcranial Magnetic Stimulation (rTMS)a 4-month maintenance procedure of sham rTMS | Device | sham rTMS |
Primary outcome
the number of times a patient is assessed as a responder
Time frame: between baseline and month 5
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Sonia Dollfus principal investigator
University Caen Normandie
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment in people with Schizophrenia; Psychosis, run by University Hospital, Caen at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sonia Dollfus, MD-PhD (02.31.06.50.18, dollfus-s@chu-caen.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the number of times a patient is assessed as a responder (time frame: between baseline and month 5). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2025; AzTrials last refreshed its copy on 7 Nov 2026.