Structural and Functional Correlates of Clinical Response to rTMS Treatment in Schizophrenia Patients With Resistant Auditory Hallucinations (TMSCCS)

February 14, 2024 updated by: Dominique JANUEL, Centre hospitalier de Ville-Evrard, France

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

45

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Neuilly-sur-Marne,, France, 93330
        • Recruiting
        • Unité de Recherche Clinique, EPS Ville Evrard
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Active Repetitive Transcranial Magnetic Stimulation (rTMS)
low-frequency (1 Hertz) rTMS
Device: 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.
Sham Comparator: Sham Repetitive Transcranial Magnetic Stimulation (rTMS)
sham TMS
Device: Sham Repetitive Transcranial Magnetic Stimulation (rTMS)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Changes in the integrity of white matter tracts between responder and non-responder patients
Time Frame: Baseline
Baseline
Changes in the variations of the blood-oxygen-dependent level (BOLD) signal between responder and non-responder patients
Time Frame: Baseline
Baseline

Secondary Outcome Measures

Outcome Measure
Time Frame
AHRS (Auditory Hallucinations Rating Scale)
Time Frame: Baseline, 3 weeks, 7 weeks and 15 weeks
Baseline, 3 weeks, 7 weeks and 15 weeks
HCS (Hallucinations Change Score)
Time Frame: Baseline, 3 weeks, 7 weeks and 15 weeks
Baseline, 3 weeks, 7 weeks and 15 weeks
PANSS (Positive And Negative Syndrome Scale)
Time Frame: Baseline, 3 weeks, 7 weeks and 15 weeks
Baseline, 3 weeks, 7 weeks and 15 weeks
PSYRATS (Psychotic Symptom Rating Scale)
Time Frame: Baseline, 3 weeks, 7 weeks and 15 weeks
Baseline, 3 weeks, 7 weeks and 15 weeks
BDI (Beck Depression Inventory)
Time Frame: Baseline, 3 weeks, 7 weeks and 15 weeks
Baseline, 3 weeks, 7 weeks and 15 weeks
Serum BDNF levels
Time Frame: Baseline, 3 weeks, 7 weeks and 15 weeks
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
Baseline, 3 weeks, 7 weeks and 15 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre hospitalier de Ville-Evrard, France

Investigators

  • Principal Investigator: Fanny Thomas, BIOLOGISTE, Unité de Recherche Clinique, EPS Ville Evrard, Neuilly-sur-Marne,, France, 93330
  • Principal Investigator: Dominique Januel, MD, PhD, Unité de Recherche Clinique, EPS Ville Evrard, Neuilly-sur-Marne,, France, 93330

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 14, 2015

Primary Completion (Estimated)

September 8, 2025

Study Completion (Estimated)

October 8, 2025

Study Registration Dates

First Submitted

April 22, 2016

First Submitted That Met QC Criteria

April 26, 2016

First Posted (Estimated)

April 29, 2016

Study Record Updates

Last Update Posted (Actual)

February 15, 2024

Last Update Submitted That Met QC Criteria

February 14, 2024

Last Verified

February 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • dmdpt6tech/mm/2014-A01595-42

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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