High Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) in Schizophrenia : a Randomized Controlled Study

NCT01022489 | Completed Phase 2 DMC

• 1 other identifier: 2008-A01589-46
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Repetitive transcranial magnetic stimulation (rTMS) is a recent therapeutic which has demonstrated its efficacy in the treatment of auditory hallucinations in patients with schizophrenic disorders. Up to now, the target of stimulation has been over the left temporoparietal region (based on the international 10-20 EEG system) and rTMS has been delivered at low frequency (1 Hz). High frequency (20 Hz) might allow shortening the duration of treatment and so could be more convenient for the patient (2 days at high frequency instead of 15 days at low frequency). Besides high frequency, an accurate target taking into account the inter-subjects anatomical variability might increase the efficacy. Based on a great overlap of language and auditory hallucinations networks, the investigators hypothesized that targeting the stimulation on the highest cluster of activation induced by a language task could be an easier and relevant method to determine the target. The investigators suggest that the best area is located at the posterior part of the left superior temporal sulcus (STS). Indeed, this area is considered as an " epicenter " of language, i.e., involved both in understanding and production of language and in the auditory hallucination network. Therefore, the investigators conducted an open pilot study in order to test the interest of rTMS at high frequency (20 Hz) associated with anatomical and functional magnetic resonance imaging (MRI) and neuronavigation in 11 schizophrenic patients with hallucinations. The investigators showed a significant reduction of auditory hallucinations; Seven out of 11 patients (63.8%) were considered as responders at day 12 with a decrease of more than 30% of the score of Hoffman's scale (Auditory Hallucinations Rating Scale) ; 2 patients presented a drastic improvement with no hallucinations after 12 days of rTMS. The investigators also showed the target based on anatomical and functional MRI was located at the intersection of the left STS and the coronal slice across the vertical line of sylvius sulcus. The aim of this multicentric double-blind study (randomized and placebo sham) is to demonstrate the efficacy of rTMS at high frequency with neuronavigation in the treatment of auditory hallucinations in patients with schizophrenia and schizo-affective disorders (DSMIV-R). Methods: 72 subjects will be included after written consent. After randomization, the subject will receive in a double blind either active treatment or placebo (sham coil) treatment. rTMS : 4 sessions of 13 minutes, with 2 sessions a day, at 20Hz frequency and at an intensity of 80% of rest motor threshold will be delivered. These parameters allow the investigators to be under the risk of epilepsia, the only one severe side effect. Another mild side effect is headache easily treated by antalgic drugs. The target will be established with anatomical MRI eventually associated with functional MRI before treatment. The efficacy of treatment will be evaluated over 4 weeks (D0, D1, D2, D7, D14, D21 and D30). The primary assessment is the percentage of patients who present a decrease of more than 30% of the frequency item of Auditory Hallucinations Rating Scale (AHRS) between D1 and D30 at 2 evaluations spaced of 1 week (Responder patients). The secondary assessments are : 1- Relative decrease of frequency item of AHRS between D1 and D14 ; 2- Evolution of total score of AHRS at D1, D2, D7, D14, D21 and D30 ; 3- Variation of scores of CGI, SUMD, IS, positive, negative, general and total PANSS scores between D0 and D14 and D30 ; 4- Scores at secondary side effects (adapted UKU) at D2 and D7; 5- Distances between the present target and the classical target based on 10-20 EEG system (T3P3) and/or the target established with functional MRI (cluster of activations induced by a listening comprehension task).

Conditions

Auditory Hallucinations in Patients With Schizophrenic Disorders

Keywords

Schizophrenia, auditory hallucinations, TMS

Outcome Measures

Primary Outcomes (1)

• The primary assessment is the percentage of patients who present a decrease of more than 30% of the frequency item of AHRS between D1 and D30 at 2 evaluations spaced of 1 week (Responder patients)

  Day 30

Study Arms (2)

Transcranial magnetic stimulation: rTMS

EXPERIMENTAL

rTMS : 4 sessions of 13 minutes, with 2 sessions a day, at 20Hz frequency and at an intensity of 80% of rest motor threshold will be delivered

Device: Transcranial magnetic stimulation: rTMS

placebo (sham coil) treatment

PLACEBO COMPARATOR

Device: Placebo (sham coil) treatment

Interventions

Transcranial magnetic stimulation: rTMS DEVICE

4 sessions of 13 minutes, with 2 sessions a day, at 20Hz frequency and at an intensity of 80% of rest motor threshold will be delivered

Transcranial magnetic stimulation: rTMS

Placebo (sham coil) treatment DEVICE

Sham coil treatment

placebo (sham coil) treatment

Eligibility Criteria

• Age: 16 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with schizophrenic disorders aged from 16 to 65 years old
• Patients suffering from auditory hallucinations (score AHRS \> 10) undergoing antipsychotic treatments
• patients clinically stabilised (no antipsychotic treatments modifications for the last 2 months
• Written signed consent

You may not qualify if:

• Pregnancy or breastfeeding
• patients with a brain tumor
• Patients with previous history of epilepsy
• Patients already treated once by rTMS
• Counter-indication to MRI or to rTMS

Sponsors & Collaborators

• University Hospital, Caen: lead

Study Sites (1)

Caen University Hospital

Caen, 14033, France

Location

Related Publications (1)

• Dollfus S, Jaafari N, Guillin O, Trojak B, Plaze M, Saba G, Nauczyciel C, Montagne Larmurier A, Chastan N, Meille V, Krebs MO, Ayache SS, Lefaucheur JP, Razafimandimby A, Leroux E, Morello R, Marie Batail J, Brazo P, Lafay N, Wassouf I, Harika-Germaneau G, Guillevin R, Guillevin C, Gerardin E, Rotharmel M, Crepon B, Gaillard R, Delmas C, Fouldrin G, Laurent G, Nathou C, Etard O. High-Frequency Neuronavigated rTMS in Auditory Verbal Hallucinations: A Pilot Double-Blind Controlled Study in Patients With Schizophrenia. Schizophr Bull. 2018 Apr 6;44(3):505-514. doi: 10.1093/schbul/sbx127.

  PMID: 29897597 RESULT

MeSH Terms

Conditions

Schizophrenia; Hallucinations

Interventions

Therapeutics

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Sonia Dollfus, MD, PhD

  University Hospital, Caen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2009
• First Posted: December 1, 2009
• Study Start: August 1, 2009
• Primary Completion: February 1, 2015
• Study Completion: March 1, 2015
• Last Updated: April 2, 2026

Record last verified: 2015-07

Locations

FR (1)