High Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) in Schizophrenia : a Randomized Controlled Study
Condition: Auditory Hallucinations in Patients With Schizophrenic Disorders
MeSH terms: Hallucinations; Schizophrenia
Study type: Interventional
Phase: Phase 2/Phase 3

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).
    


Intervention name(s): Transcranial magnetic stimulation: rTMS; Placebo (sham coil) treatment
Intervention type(s): Device; Device
Intervention description(s): 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; Sham coil treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Schizophrenia, auditory hallucinations, TMS