SchizophreniaTMSCCSNCT02755623
Structural and Functional Correlates of Clinical Response to rTMS Treatment in Schizophrenia Patients With Resistant Auditory Hallucinations
A study testing Repetitive Transcranial Magnetic Stimulation (rTMS) in people with Schizophrenia, run by Centre hospitalier de Ville-Evrard, France at 1 site in France.
Trial summary
The potential of non-invasive Transcranial Magnetic Stimulation (TMS) as a therapeutic tool for improving schizophrenic symptoms, in particular resistant hallucinations, has been increasingly studied over the past decades. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Repetitive Transcranial Magnetic Stimulation (rTMS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 1 siteFrance
- Study dates
- 14 Oct 2015to 8 Oct 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- Patient with a diagnosis of schizophrenia according to DSM-V (Diagnostic and Statistical Manual of Mental Disorder V, 2013) criteria
- Clinically stabilized for at least 3 months
- Patient with resistant auditory hallucinations
- Male or female, 18 to 65 years old
- A written agreement from the patient's legal guardian/s, if applicable
- Right-handed
- A good knowledge of the French language
- Signed consent form
Who cannot join
- Other diseases than schizophrenia
- Indulging in an addiction (alcohol, psychoactive substances) over the last 12 months
- Patient who has received rTMS treatment in the last 12 months
- Patient who is participating in a concurrent research protocol
- Patient with a history of seizures
- rTMS contraindications: patient with epilepsy, brain surgery and/or head trauma in the past, use of cardiac pacemaker, or surgical staples on the scalp
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- MRI contraindications: pregnancy or lactating (n.b. a negative pregnancy test will be required if the patient is a female in reproductive years who does not use contraception); use of cardiac pace maker or surgical staples; patient with a neurological disorder, head trauma or claustrophobia
- Patient with severe cardiovascular disease
- Patient with medication which reduces the epileptic threshold (bupropion, methadone and theophylline)
- Patients placed in psychiatric care either by the state or a third party
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Unité de Recherche Clinique, EPS Ville Evrard
Neuilly-sur-Marne, 93330
OURRAD AREZKI, CRA, 0143093030, urcve1@gmail.com
About this study
Official title: Structural and Functional Correlates of Clinical Response to Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment in Schizophrenia Patients With Resistant Auditory Hallucinations
The potential of non-invasive Transcranial Magnetic Stimulation (TMS) as a therapeutic tool for improving schizophrenic symptoms, in particular resistant hallucinations, has been increasingly studied over the past decades. Several studies have demonstrated that low-frequency patterns of repetitive TMS (rTMS) applied over the left Temporoparietal Junction (TPJ), which are known to decrease local activity, significantly reduced auditory verbal hallucinations in schizophrenic patients. In spite of highly promising results, a high level of inter-individual variability in the responses to non-invasive brain stimulation treatments, and the fact that rTMS may prove ineffective in some patients, keep spurring controversy about the efficacy of these approaches (as currently performed), as well as about how to increase its efficacy and consistency. Accordingly, the objectives of this project are to better understand the impact of rTMS on the brains of patients with resistant auditory hallucinations, and to use this information not only to better understand this condition but to develop more efficient and consistent therapies. Thus, in this study, the investigators focus more specifically on resistant auditory hallucinations in schizophrenia, which is a common symptom in schizophrenic patients, and can be treated by rTMS. The investigators hypothesize that there is a baseline difference in anatomical and/or functional connectivity between responder and non-responder patients who are treated with rTMS. Therefore, our project will aim to determine some anatomical and functional connectivity markers of response to rTMS treatment in patients with schizophrenia
Read the detailed description
The potential of non-invasive Transcranial Magnetic Stimulation (TMS) as a therapeutic tool for improving schizophrenic symptoms, in particular resistant hallucinations, has been increasingly studied over the past decades. Several studies have demonstrated that low-frequency patterns of repetitive TMS (rTMS) on the left temporoparietal junction (TPJ), which are known to decrease local activity, significantly reduce auditory verbal hallucinations in schizophrenic patients. In spite of highly promising results, a high level of inter-individual variability in the response to non-invasive brain stimulation treatments, and the fact that rTMS may prove ineffective in some patients, keep spurring controversy on the efficacy of these approaches as currently performed, and on how to increase its efficacy and consistency. To date, few studies have aimed to explain this variability when, in fact, a better understanding of this common phenomena in the neurostimulation domain would clearly increase the effectiveness of this treatment, and lead to individualized therapeutic approaches specifically tailored to the conditions of each patient. Moreover, many questions stand, particularly regarding the influence of rTMS treatment on the anatomical and functional connectivity in schizophrenic patients.
Accordingly, the objectives of this project are to better understand the impact of rTMS on the brains of patients with resistant auditory hallucinations, and to use this information not only to better understand this condition but to develop more efficient and consistent therapies. The investigators hypothesize that there is a baseline difference in anatomical and/or functional connectivity between responder and non-responder patients who are treated with rTMS. Therefore, this project aims to determine some anatomical and functional connectivity markers of response to rTMS treatment in patients with schizophrenia. For this, the investigators compare the patterns of diffusion tensor imaging (DTI) white matter tractography and resting-state functional magnetic resonance imaging (fMRI) data between responder and non-responder patients to rTMS treatment. Moreover, the investigators believe that rTMS can increase the functional connectivity between frontal and temporo-parietal cortices in schizophrenic patients associated with improvements in auditory hallucinations. Therefore, the second objectives of this work are to evaluate the impact of rTMS in functional connectivity in patients with schizophrenia by comparing the DTI and resting-state fMRI data before and after rTMS treatment in both responder and non-responder patients.
- Conditions
- Schizophrenia
- Being tested
- Repetitive Transcranial Magnetic Stimulation (rTMS), Sham Repetitive Transcranial Magnetic Stimulation (rTMS)
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Repetitive Transcranial Magnetic Stimulation (rTMS)Device
Participants are sequentially randomly assigned to either 20 active rTMS sessions or 20 sham rTMS sessions that were applied over the left temporoparietal junction. Treatments are administered daily, over a period of two weeks.
Sham Repetitive Transcranial Magnetic Stimulation (rTMS)Device
| Study group | Role | What they receive |
|---|---|---|
| Active Repetitive Transcranial Magnetic Stimulation (rTMS) | Active comparator | low-frequency (1 Hertz) rTMS Receives: Device: Repetitive Transcranial Magnetic Stimulation (rTMS) |
| Sham Repetitive Transcranial Magnetic Stimulation (rTMS) | Sham comparator | sham TMS Receives: Device: Sham Repetitive Transcranial Magnetic Stimulation (rTMS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in the integrity of white matter tracts between responder and non-responder patients
Measured: Baseline
Changes in the variations of the blood-oxygen-dependent level (BOLD) signal between responder and non-responder patients
Measured: Baseline
Secondary outcomes (7)
AHRS (Auditory Hallucinations Rating Scale)
Measured: Baseline, 3 weeks, 7 weeks and 15 weeks
HCS (Hallucinations Change Score)
Measured: Baseline, 3 weeks, 7 weeks and 15 weeks
PANSS (Positive And Negative Syndrome Scale)
Measured: Baseline, 3 weeks, 7 weeks and 15 weeks
PSYRATS (Psychotic Symptom Rating Scale)
Measured: Baseline, 3 weeks, 7 weeks and 15 weeks
BDI (Beck Depression Inventory)
Measured: Baseline, 3 weeks, 7 weeks and 15 weeks
Serum BDNF levels
Measured: Baseline, 3 weeks, 7 weeks and 15 weeks
Measure of the amplitude of Motor-Evoked Potentials (MEPs)
Measured: Baseline, 3 weeks, 7 weeks and 15 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2016 (estimated)
- Study start14 Oct 2015
- Primary completion8 Sep 2025 (estimated)
- Study completion8 Oct 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre hospitalier de Ville-Evrard, France
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dominique JANUEL, Centre hospitalier de Ville-Evrard, France
- Investigators
- Fanny Thomas, BIOLOGISTE, Principal investigator, Unité de Recherche Clinique, EPS Ville Evrard, Neuilly-sur-Marne,, France, 93330Dominique Januel, MD, PhD, Principal investigator, Unité de Recherche Clinique, EPS Ville Evrard, Neuilly-sur-Marne,, France, 93330
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02755623
- Sponsor's protocol ID
- dmdpt6tech/mm/2014-A01595-42
- Acronym
- TMSCCS
- Status last verified
- Feb 2023
- First submitted
- 22 Apr 2016
- Last updated
- 15 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Thomas F, Bouaziz N, Gallea C, Schenin-King Andrianisaina P, Durand F, Bollore O, Benadhira R, Isaac C, Braha-Zeitoun S, Moulier V, Valero-Cabre A, Januel D. Structural and functional brain biomarkers of clinical response to rTMS of medication-resistant auditory hallucinations in schizophrenia patients: study protocol for a randomized sham-controlled double-blind clinical trial. Trials. 2019 Apr 23;20(1):229. doi: 10.1186/s13063-019-3311-x.
PubMed 31014369
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Structural and Functional Correlates of Clinical Response to Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment in Schizophrenia Patients With Resistant Auditory Hallucinations
- ClinicalTrials.gov ID
- NCT02755623
- Acronym / sponsor ID
- TMSCCS / dmdpt6tech/mm/2014-A01595-42
- Conditions
- Schizophrenia
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Centre hospitalier de Ville-Evrard, FranceUniversity, hospital or other
- Study start
- 14 Oct 2015 (actual)
- Primary completion
- 8 Sep 2025 (estimated)
- Study completion
- 8 Oct 2025 (estimated)
- First posted
- 29 Apr 2016 (estimated)
- 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.
The potential of non-invasive Transcranial Magnetic Stimulation (TMS) as a therapeutic tool for improving schizophrenic symptoms, in particular resistant hallucinations, has been increasingly studied over the past decades. Several studies have demonstrated that low-frequency patterns of repetitive TMS (rTMS) applied over the left Temporoparietal Junction (TPJ), which are known to decrease local activity, significantly reduced auditory verbal hallucinations in schizophrenic patients. In spite of highly promising results, a high level of inter-individual variability in the responses to non-invasive brain stimulation treatments, and the fact that rTMS may prove ineffective in some patients, keep spurring controversy about the efficacy of these approaches (as currently performed), as well as about how to increase its efficacy and consistency. Accordingly, the objectives of this project are to better understand the impact of rTMS on the brains of patients with resistant auditory hallucinations, and to use this information not only to better understand this condition but to develop more efficient and consistent therapies. Thus, in this study, the investigators focus more specifically on resistant auditory hallucinations in schizophrenia, which is a common symptom in schizophrenic patients, and can be treated by rTMS. The investigators hypothesize that there is a baseline difference in anatomical and/or functional connectivity between responder and non-responder patients who are treated with rTMS. Therefore, our project will aim to determine some anatomical and functional connectivity markers of response to rTMS treatment in patients with schizophrenia
Detailed description
The potential of non-invasive Transcranial Magnetic Stimulation (TMS) as a therapeutic tool for improving schizophrenic symptoms, in particular resistant hallucinations, has been increasingly studied over the past decades. Several studies have demonstrated that low-frequency patterns of repetitive TMS (rTMS) on the left temporoparietal junction (TPJ), which are known to decrease local activity, significantly reduce auditory verbal hallucinations in schizophrenic patients. In spite of highly promising results, a high level of inter-individual variability in the response to non-invasive brain stimulation treatments, and the fact that rTMS may prove ineffective in some patients, keep spurring controversy on the efficacy of these approaches as currently performed, and on how to increase its efficacy and consistency. To date, few studies have aimed to explain this variability when, in fact, a better understanding of this common phenomena in the neurostimulation domain would clearly increase the effectiveness of this treatment, and lead to individualized therapeutic approaches specifically tailored to the conditions of each patient. Moreover, many questions stand, particularly regarding the influence of rTMS treatment on the anatomical and functional connectivity in schizophrenic patients.
Accordingly, the objectives of this project are to better understand the impact of rTMS on the brains of patients with resistant auditory hallucinations, and to use this information not only to better understand this condition but to develop more efficient and consistent therapies. The investigators hypothesize that there is a baseline difference in anatomical and/or functional connectivity between responder and non-responder patients who are treated with rTMS. Therefore, this project aims to determine some anatomical and functional connectivity markers of response to rTMS treatment in patients with schizophrenia. For this, the investigators compare the patterns of diffusion tensor imaging (DTI) white matter tractography and resting-state functional magnetic resonance imaging (fMRI) data between responder and non-responder patients to rTMS treatment. Moreover, the investigators believe that rTMS can increase the functional connectivity between frontal and temporo-parietal cortices in schizophrenic patients associated with improvements in auditory hallucinations. Therefore, the second objectives of this work are to evaluate the impact of rTMS in functional connectivity in patients with schizophrenia by comparing the DTI and resting-state fMRI data before and after rTMS treatment in both responder and non-responder patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active Repetitive Transcranial Magnetic Stimulation (rTMS) | Active comparator | Device: Repetitive Transcranial Magnetic Stimulation (rTMS)low-frequency (1 Hertz) rTMS |
| Sham Repetitive Transcranial Magnetic Stimulation (rTMS) | Sham comparator | Device: Sham Repetitive Transcranial Magnetic Stimulation (rTMS)sham TMS |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patient with a diagnosis of schizophrenia according to DSM-V (Diagnostic and Statistical Manual of Mental Disorder V, 2013) criteria
- Clinically stabilized for at least 3 months
- Patient with resistant auditory hallucinations
- Male or female, 18 to 65 years old
- A written agreement from the patient's legal guardian/s, if applicable
Key exclusion criteria (10 listed)
- Other diseases than schizophrenia
- Indulging in an addiction (alcohol, psychoactive substances) over the last 12 months
- Patient who has received rTMS treatment in the last 12 months
- Patient who is participating in a concurrent research protocol
- Patient with a history of seizures
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)Participants are sequentially randomly assigned to either 20 active rTMS sessions or 20 sham rTMS sessions that were applied over the left temporoparietal junction. Treatments are administered daily, over a period of two weeks. | Device | Active Repetitive Transcranial Magnetic Stimulation (rTMS) |
| Sham Repetitive Transcranial Magnetic Stimulation (rTMS) | Device | Sham Repetitive Transcranial Magnetic Stimulation (rTMS) |
Primary outcome
Changes in the integrity of white matter tracts between responder and non-responder patients
Time frame: Baseline
Changes in the variations of the blood-oxygen-dependent level (BOLD) signal between responder and non-responder patients
Time frame: Baseline
7 secondary outcomes
AHRS (Auditory Hallucinations Rating Scale)
Time frame: Baseline, 3 weeks, 7 weeks and 15 weeks
HCS (Hallucinations Change Score)
Time frame: Baseline, 3 weeks, 7 weeks and 15 weeks
PANSS (Positive And Negative Syndrome Scale)
Time frame: Baseline, 3 weeks, 7 weeks and 15 weeks
PSYRATS (Psychotic Symptom Rating Scale)
Time frame: Baseline, 3 weeks, 7 weeks and 15 weeks
BDI (Beck Depression Inventory)
Time frame: Baseline, 3 weeks, 7 weeks and 15 weeks
Serum BDNF levels
Time frame: Baseline, 3 weeks, 7 weeks and 15 weeks
Measure of the amplitude of Motor-Evoked Potentials (MEPs)
Time frame: Baseline, 3 weeks, 7 weeks and 15 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2024.
- Derived from this study: PubMed 31014369Thomas F, Bouaziz N, Gallea C, Schenin-King Andrianisaina P, Durand F, Bollore O, Benadhira R, Isaac C, Braha-Zeitoun S, Moulier V, Valero-Cabre A, Januel D. Structural and functional brain biomarkers of clinical response to rTMS of medication-resistant auditory hallucinations in schizophrenia patients: study protocol for a randomized sham-controlled double-blind clinical trial. Trials. 2019 Apr 23;20(1):229. doi: 10.1186/s13063-019-3311-x.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Fanny Thomas, BIOLOGISTE principal investigator
Unité de Recherche Clinique, EPS Ville Evrard, Neuilly-sur-Marne,, France, 93330
Dominique Januel, MD, PhD principal investigator
Unité de Recherche Clinique, EPS Ville Evrard, Neuilly-sur-Marne,, France, 93330
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) in people with Schizophrenia, run by Centre hospitalier de Ville-Evrard, France 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 8 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 15 Feb 2024. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Arezki Ourrad (+33143093232, urcve1@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in the integrity of white matter tracts between responder and non-responder patients (time frame: Baseline). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02755623, which also lists 1 linked publication.
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 15 Feb 2024.