Multimodal MRI-guided rTMS to Treat Refractory Hallucinations

Study Overview
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Brief Summary
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The efficacy of neuro-navigated rTMS for patients with schizophrenia suffering from drug-resistant multisensory hallucinations will be tested by the implementation of a double-blind randomized controlled trial (RCT) This study will use a combination of different MRI modalities (fMRI and DTI) to define with precision rTMS brain-targets in the case of multisensory hallucinations The investigators anticipate that multimodal MRI-guided rTMS will allow a significant improvement in the efficacy of neuromodulation treatment of refractory hallucinations

Official Title
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Multimodal MRI-guided Repetitive Transcranial Magnetic Stimulation to Treat Drug-resistant Hallucinations: a Randomized Control Trial

Conditions
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Hallucinations, Schizophrenia, Perceptual Disorders

Intervention / Treatment
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* Device: MagPro X100 repetitive Transcranial Magnetic Stimulation
* Device: MagPro X100 repetitive Transcranial Magnetic Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Right-handed Female/Male, [13-60 y.o.], Schizophrenia (DSM-IV-TR diagnosis), Drug-resistant hallucinations (Kinon & Kane criteria, 1993), Unmodified antipsychotic dosage during the 30 days preceding rMTS, No anticonvulsive medication, No neurological disorder, no addictive behavior, Matched for sex, age and PANSS scores, Consent to participate to the study, Exclusion Criteria: Pregnancy Contraindication to MRI scan Contraindication to rTMS treatment Claustrophobia No social insurance

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Multimodal MRI-guided rTMS<br> | Device: MagPro X100 repetitive Transcranial Magnetic Stimulation<br>* Target defined using both fMRI during hallucinations occurence and tractography. Parameters: 1 Hz/ 100% of the Motor Threshold/ 10 sessions (2/ day over 5 days)/ 1200 pulses/ session<br>|
| Active Comparator: Conventional T3-P3 rTMS<br> | Device: MagPro X100 repetitive Transcranial Magnetic Stimulation<br>* Target: T3-P3 (10-20 EEG international System). Parameters: 1 Hz/ 100% of the Motor Threshold/ 10 sessions (2/ day over 5 days)/ 1200 pulses/ session<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity and Frequency of Hallucinations | Visual Analogue Scale (Severity)/ Visual Analogue Scale (Frequency rate) | Assessed at baseline (t0) and longitudinally after the 10 rTMS sessions during the following month (D+15, M+1, M+3, M+6, M+12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical State | Clinical Global Improvement [CGI]/ Positive & Negative Symptoms Scale [PANSS]/ Global Assessment of Functioning [GAF]. For the auditory modality: Add the Auditory Hallucinations rating Scale [AHRS] frequency scale and total score/ Add the computerized Binary Scale of Auditory Speech Hallucinations [cbSASH] | Assessed at baseline (t0) and longitudinally after the 10 rTMS sessions during the following month (D+15, M+1, M+3, M+6, M+12) | 
| MRI changes | structural MRI/ functional MRI/ Diffusion Tensor Imaging/ MR-spectroscopy | Assessed at baseline (t0) and 1 month after the rTMS sessions (M+1) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Repetitive Transcranial Magnetic Stimulation, Neuronavigation, Functional Magnetic Resonance Imaging, Diffusion Tensor Imaging