Treatment Resistant SchizophreniaHALLUSTIMNCT06361160
Reduction of Auditory-Verbal Hallucinations in Schizophrenia Through Cortical Neuromodulation
A study testing Active Transcranial Magnetic Stimulation (TMS) in people with Treatment Resistant Schizophrenia, run by Centre Hospitalier St Anne at 1 site in France.
Trial summary
Approximately 1% of the general population will be affected by schizophrenia over the course of their lives, with life expectancy being reduced by 20 years on average and quality of life being severely diminished in affected individuals. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Treatment Resistant Schizophrenia
- What is being tested?
- Active Transcranial Magnetic Stimulation (TMS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteFrance
- Study dates
- 21 May 2024to Sep 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age > 18 years old
- Schizophrenic Disorder (Diagnostic and statistical manual of mental disorders, DSM-5-TR, American Psychiatric Association, 2013)
- AVHs that have resisted to at least two properly conducted antipsychotic therapies at an effective dose for at least 8 weeks (criteria of Kinon et al., 1993)
- Frequent AVHs (at least 10 times per hour) (Fovet et al., 2022)
- Unmodified antipsychotic dosage for 30 days prior to inclusion in the protocol
- AVH are the main residual symptom of schizophrenia.
- Consent to participate in the study
Who cannot join
- Pregnancy (based on date of last menstrual period with possibility of urine test if in doubt)
- Anticonvulsant therapy
- Neurological disorder (e.g., multiple sclerosis, epilepsy)
- Current addictive behavior (except tobacco and cannabis, widely used in this clinical population; Fovet et al., 2022)
- Contraindication to MRI (i.e., presence of ferromagnetic material or implanted neurostimulation devices due to the risk of displacement or dysfunction such as cochlear implants, cardiac pacemakers, metal splinters in the body following an accident, permanent makeup applied less than 6 months ago, neurosurgical clips, deep brain or vagus nerve stimulation devices, baclofen pumps) (Lefaucheur et al., 2011)
- Morphological criteria: weight > 130 Kg, abdominal circumference conditioned by the opening of the magnet, shoulder width
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- Lack of coverage by the social security system
- Current participation in another interventional research protocol or being in the exclusion period of a previous research protocol
- Refusal to be informed of an brain anomaly detected in the MRI
- Person under guardianship or curatorship
- Behavioral disorders or delusions likely to prevent the MRI or rTMS from being performed under good conditions (left to the discretion of the investigator at baseline).
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
Groupe Hospitalo-Universitaire Paris Psychiatrie & Neurosciences
Paris
Khaoussou Sylla, Dr, K.SYLLA@ghu-paris.fr
Philippe Domenech, Pr
About this study
Official title: Reduction of Auditory-Verbal Hallucinations in Schizophrenia Through Cortical Neuromodulation: Towards a Closed-loop System
Approximately 1% of the general population will be affected by schizophrenia over the course of their lives, with life expectancy being reduced by 20 years on average and quality of life being severely diminished in affected individuals. One third of patients suffering from schizophrenia will evolve towards a resistant form of the disease, amongst which many will suffer from auditory-verbal hallucinations (AVH) that current therapeutic approaches struggle to alleviate. Previous work from our team has demonstrated the possibility of robustly inferring the periods of occurrence of AVH from fMRI data, paving the way for the development of a closed-loop neuromodulation system comprised of an electrode array positioned in Broca's area, which would detect AVH in real time, and effector electrodes which would stimulate the temporo-parietal cortex to interrupt them. The aim of this project is to assess the feasibility of this system. To do so, we will first test the ability of transcranial magnetic stimulation of the "continuous theta burst" (cTBS) type, applied at the time of AVH onset, to reduce their duration and intensity, and assess whether this is associated with therapeutic response to the current gold standard rTMS protocol for AVH reduction through neuroplasticity induction. Demonstrating the feasibility of acute suppression of AVH by cortical neurostimulation is an essential element in the feasibility of a closed-loop reactive neuromodulation system.
The research project comprises two phases:
Read more
-Phase 1: randomized controlled clinical trial (1 weekly session per patient over 12 weeks: 6 active stimulation sessions and 6 sham sessions) evaluating the phasic effects of rTMS on AVHs as they appear during the sessions.
Phase 2: open-label study offering patients a routine rTMS protocol which has demonstrated its effects on AVH (10 TMS sessions over one workweek - twice daily with 1-hour intervals, MULTIMODHAL study, NCT01373866).
- Conditions
- Treatment Resistant Schizophrenia
- Being tested
- Active Transcranial Magnetic Stimulation (TMS), Sham Transcranial Magnetic Stimulation (TMS)
- Keywords
- Treatment Resistant Schizophrenia, Transcranial Magnetic Stimulation (TMS)
- Medical subject headings
- Schizophrenia, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active Transcranial Magnetic Stimulation (TMS)Device
Also called Active TMS
Active rTMS (continuous theta burst, cTBS) applied to the temporo-parietal junction (TPJ) at the onset of the Auditory Verbal Hallucinations (AVH).
Sham Transcranial Magnetic Stimulation (TMS)Device
Also called Sham TMS
Sham rTMS (continuous theta burst, cTBS) applied to the temporo-parietal junction (TPJ) during the onset of the Auditory Verbal Hallucinations (AVH).
An electrical stimulator is synchronised with the magnetic stimulation to recreate the tactile sensation and the coils emits the same noise during sham stimulation as in the active configuration, making it impossible to distinguish between active and placebo magnetic stimulation.
| Study group | Role | What they receive |
|---|---|---|
| Active TMS sessions | Active comparator | For a given patient, the 6 sessions (out of 12) in which the TMS is active. Receives: Device: Active Transcranial Magnetic Stimulation (TMS) |
| Sham TMS sessions | Sham comparator | For a given patient, the 6 sessions (out of 12) in which the TMS is a sham. Receives: Device: Sham Transcranial Magnetic Stimulation (TMS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Duration of auditory-verbal hallucinations
The primary endpoint is the reduction in the duration of AVH (in seconds) during active phasic stimulation sessions compared to sham sessions. Participants will press a button when an AVH occurs (starting the intervention) and press another when the AVH disappears. This allows for the recording of the duration of the AVHs.
Measured: During the intervention of Phase 1 (for each active or sham TMS session)
Secondary outcomes (3)
Clinical scales scores
An evaluation of the following clinical measures will take place : AHRS, CGI, Visual analog scale for AVH intensity and frequency, GAF and PANSS.
Measured: At baseline (before Phase 1), before the intervention of Phase 2 (Day 0, two weeks after the end of Phase 1), after the intervention of Phase 2 (Day 15, Month 1, Month 3, Month 6, Month 12)
Measure of the duration and/or intensity of HAV (in seconds) during active phasic stimulation sessions compared to sham sessions (phase 1) among TMS responders and non-responders in phase 2
Reduction in duration and/or intensity of HAV (in seconds) during active phasic stimulation sessions compared to sham sessions (phase 1) among TMS responders and non-responders in phase 2 (response: decrease in pre/post AHRS score >25%).
Measured: Through study completion, an average of 2 years
Intensity of auditory-verbal hallucinations
Phase 1 At the end of each active or sham cTBS train, the computer screen will display an 5-point Likert Scale, through which the patient will have to report AVH-intensity before the session can continue.
Measured: During the intervention of Phase 1 (for each active or sham TMS session)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2024
- Study start21 May 2024
- Primary completionSep 2027 (estimated)
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Treatment Resistant SchizophreniaStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier St AnneThe 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
- Crossover
- Model description
- Patients (20) suffering from resistant schizophrenia will be enrolled over a 12-month period and will be randomized in a (1:1) ratio to start with either active or sham Transcranial Magnetic Stimulation (TMS) for the first of their 12 sessions, which will then alternate from one condition to the other for each patient.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier St Anne
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Philippe Domenech, MD, PhD, Principal investigator, GHU Paris Psychiatry & Neurosciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06361160
- Sponsor's protocol ID
- D23-P037
- Acronym
- HALLUSTIM
- Status last verified
- Sep 2026
- First submitted
- 29 Mar 2024
- Last updated
- 21 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reduction of Auditory-Verbal Hallucinations in Schizophrenia Through Cortical Neuromodulation: Towards a Closed-loop System
- ClinicalTrials.gov ID
- NCT06361160
- Acronym / sponsor ID
- HALLUSTIM / D23-P037
- Conditions
- Treatment Resistant Schizophrenia
- Keywords
- Treatment Resistant Schizophrenia, Transcranial Magnetic Stimulation (TMS)
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Centre Hospitalier St AnneUniversity, hospital or other
- Study start
- 21 May 2024 (actual)
- Primary completion
- Sep 2027 (estimated)
- Study completion
- Sep 2027 (estimated)
- First posted
- 11 Apr 2024 (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.
Approximately 1% of the general population will be affected by schizophrenia over the course of their lives, with life expectancy being reduced by 20 years on average and quality of life being severely diminished in affected individuals. One third of patients suffering from schizophrenia will evolve towards a resistant form of the disease, amongst which many will suffer from auditory-verbal hallucinations (AVH) that current therapeutic approaches struggle to alleviate. Previous work from our team has demonstrated the possibility of robustly inferring the periods of occurrence of AVH from fMRI data, paving the way for the development of a closed-loop neuromodulation system comprised of an electrode array positioned in Broca's area, which would detect AVH in real time, and effector electrodes which would stimulate the temporo-parietal cortex to interrupt them. The aim of this project is to assess the feasibility of this system. To do so, we will first test the ability of transcranial magnetic stimulation of the "continuous theta burst" (cTBS) type, applied at the time of AVH onset, to reduce their duration and intensity, and assess whether this is associated with therapeutic response to the current gold standard rTMS protocol for AVH reduction through neuroplasticity induction. Demonstrating the feasibility of acute suppression of AVH by cortical neurostimulation is an essential element in the feasibility of a closed-loop reactive neuromodulation system.
The research project comprises two phases:
-Phase 1: randomized controlled clinical trial (1 weekly session per patient over 12 weeks: 6 active stimulation sessions and 6 sham sessions) evaluating the phasic effects of rTMS on AVHs as they appear during the sessions.
Phase 2: open-label study offering patients a routine rTMS protocol which has demonstrated its effects on AVH (10 TMS sessions over one workweek - twice daily with 1-hour intervals, MULTIMODHAL study, NCT01373866).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
- Model description
- Patients (20) suffering from resistant schizophrenia will be enrolled over a 12-month period and will be randomized in a (1:1) ratio to start with either active or sham Transcranial Magnetic Stimulation (TMS) for the first of their 12 sessions, which will then alternate from one condition to the other for each patient.
| Arm | Type | Receives |
|---|---|---|
| Active TMS sessions | Active comparator | Device: Active Transcranial Magnetic Stimulation (TMS)For a given patient, the 6 sessions (out of 12) in which the TMS is active. |
| Sham TMS sessions | Sham comparator | Device: Sham Transcranial Magnetic Stimulation (TMS)For a given patient, the 6 sessions (out of 12) in which the TMS is a sham. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age > 18 years old
- Schizophrenic Disorder (Diagnostic and statistical manual of mental disorders, DSM-5-TR, American Psychiatric Association, 2013)
- AVHs that have resisted to at least two properly conducted antipsychotic therapies at an effective dose for at least 8 weeks (criteria of Kinon et al., 1993)
- Frequent AVHs (at least 10 times per hour) (Fovet et al., 2022)
- Unmodified antipsychotic dosage for 30 days prior to inclusion in the protocol
Key exclusion criteria (11 listed)
- Pregnancy (based on date of last menstrual period with possibility of urine test if in doubt)
- Anticonvulsant therapy
- Neurological disorder (e.g., multiple sclerosis, epilepsy)
- Current addictive behavior (except tobacco and cannabis, widely used in this clinical population; Fovet et al., 2022)
- Contraindication to MRI (i.e., presence of ferromagnetic material or implanted neurostimulation devices due to the risk of displacement or dysfunction such as cochlear implants, cardiac pacemakers, metal splinters in the body following an accident, permanent makeup applied less than 6 months ago, neurosurgical clips, deep brain or vagus nerve stimulation devices, baclofen pumps) (Lefaucheur et al., 2011)
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 |
|---|---|---|
| Active Transcranial Magnetic Stimulation (TMS)Also: Active TMSActive rTMS (continuous theta burst, cTBS) applied to the temporo-parietal junction (TPJ) at the onset of the Auditory Verbal Hallucinations (AVH). | Device | Active TMS sessions |
| Sham Transcranial Magnetic Stimulation (TMS)Also: Sham TMSSham rTMS (continuous theta burst, cTBS) applied to the temporo-parietal junction (TPJ) during the onset of the Auditory Verbal Hallucinations (AVH). An electrical stimulator is synchronised with the magnetic stimulation to recreate the tactile sensation and the coils emits the same noise during sham stimulation as in the active configuration, making it impossible to distinguish between active and placebo magnetic stimulation. | Device | Sham TMS sessions |
Primary outcome
Duration of auditory-verbal hallucinations
Time frame: During the intervention of Phase 1 (for each active or sham TMS session)
The primary endpoint is the reduction in the duration of AVH (in seconds) during active phasic stimulation sessions compared to sham sessions. Participants will press a button when an AVH occurs (starting the intervention) and press another when the AVH disappears. This allows for the recording of the duration of the AVHs.
3 secondary outcomes
Clinical scales scores
Time frame: At baseline (before Phase 1), before the intervention of Phase 2 (Day 0, two weeks after the end of Phase 1), after the intervention of Phase 2 (Day 15, Month 1, Month 3, Month 6, Month 12)
Measure of the duration and/or intensity of HAV (in seconds) during active phasic stimulation sessions compared to sham sessions (phase 1) among TMS responders and non-responders in phase 2
Time frame: Through study completion, an average of 2 years
Intensity of auditory-verbal hallucinations
Time frame: During the intervention of Phase 1 (for each active or sham TMS 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 21 Sep 2026.
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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.
Philippe Domenech, MD, PhD principal investigator
GHU Paris Psychiatry & Neurosciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active Transcranial Magnetic Stimulation (TMS) in people with Treatment Resistant Schizophrenia, run by Centre Hospitalier St Anne 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 7 inclusion and 11 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 21 Sep 2026. 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 Philippe Domenech, MD, PhD ((0)1 49 81 22 01 ext. +(33), philippe.domenech@ghu-paris.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Duration of auditory-verbal hallucinations (time frame: During the intervention of Phase 1 (for each active or sham TMS session)). 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 21 Sep 2026.