Auditory Hallucinations in Patients With Schizophrenic Disorders Clinical Trial
— TMS-HzOfficial title:
Evaluation of Repetitive Transcranial Magnetic Stimulation (rTMS) at High Frequency With Neuronavigation in the Treatment of Auditory Hallucinations : A Randomized Multicentric Controlled Study
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).
| Status | Completed |
| Enrollment | 72 |
| Est. completion date | March 2015 |
| Est. primary completion date | February 2015 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 16 Years to 65 Years |
| Eligibility |
Inclusion Criteria: - 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 Exclusion Criteria: - 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 |
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Outcomes Assessor), Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| France | Caen University Hospital | Caen |
| Lead Sponsor | Collaborator |
|---|---|
| University Hospital, Caen |
France,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | No |