A Double-Blind Placebo Controlled Trial of Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of Negative Symptoms in Schizophrenia

Study Overview
=================
Brief Summary
-----------------
There is pilot data to suggest the therapeutic value of rTMS applied to the left prefrontal cortex in the treatment of negative symptoms. Neuroimaging studies demonstrate abnormal activity in this region in patients experiencing negative symptoms. Finally rTMS applied at high frequency shows the capacity to up-regulate cortical activity in a way that would provide an explanation for a therapeutic response. The study involves participants receiving 15 sessions of high frequency rTMS treatment applied bilaterally to the prefrontal cortex over a 3 week period or sham rTMS. Following this double blind phase, participants randomised to placebo treatment will be offered 15 sessions of active treatment. In addition, ppTMS (paired pulse TMS) will be conducted prior to the onset of treatment and after completion of the course, as a means of measuring cortical inhibition and facilitation. NIRS (Near Infra red spectroscopy) will also be conducted prior to, during and after the first and last treatment sessions to allow monitoring of oxygenated and deoxygenated haemoglobin.

Detailed Description
-----------------
The main outcome measure used is the SANS (Scale for the Assessment of Negative Symptoms. This is a semi strucutured interview which provides scores from 0-70. This is administered at baseline, week 2, 3, 5 and 6. Other outcome measures administered are (frequency mentioned above): PANSS (Positive and Negative Syndrome Scale) and the Calgery Depression Scale for Schizophrenia, A cognitive battery is also administered. Inclusion Criteria: Diagnostic and Statistical Manual-IV diagnosis of schizophrenia or schizoaffective disorder, age over 18 Persistent negative symptoms of moderate to severe intensity Failure to respond to a minimum of two antipsychotic medications No increase or initiation of new antipsychotic therapy in the four weeks prior to entering the trial Exclusion Criteria Prominent positive symptoms Have an unstable medical condition, neurological disorder or any history of seizure disorder or are currently pregnant or lactating Previous brain injury or surgery, any metal clips, plates or other metal items in the head, cardiac pacemaker Subjects at high risk of violence or suicide as determined by the investigator and treating clinicians Substance dependence

Official Title
-----------------
A Double-Blind Placebo Controlled Trial of Repetitive Transcranial Magentic Stimulation (rTMS) in the Treatment of Negative Symptoms in Schizophrenia and Related Disorders

Conditions
-----------------
Schizophrenia

Intervention / Treatment
-----------------
* Device: Transcranial Magnetic Stimulation
* Device: sham TMS


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: DSM-IV diagnosis of schizophrenia or schizoaffective disorder, age over 18 Persistent negative symptoms of moderate to severe intensity Failure to respond to a minimum of two antipsychotic medications No increase or initiation of new antipsychotic therapy in the four weeks prior to entering the trial Exclusion Criteria: Prominent positive symptoms Have an unstable medical condition, neurological disorder or any history of seizure disorder or are currently pregnant or lactating Previous brain injury or surgery, any metal clips, plates or other metal items in the head, cardiac pacemaker Subjects at high risk of violence or suicide as determined by the investigator and treating clinicians Substance dependence

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active Treatment<br>Bilateral high frequency (10 Hertz) rTMS | Device: Transcranial Magnetic Stimulation<br>* Participants were sequentially randomly assigned to either 15 active bilateral treatments or 15 sham bilateral treatments that were administered on a daily basis, five days per week.<br>|
| Sham Comparator: Sham rTMS<br>Bilateral Sham rTMS | Device: sham TMS<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Scale for the Asessment of Negative Symptoms (SANS) | Scale for Assessment of Negative Symptoms [SANS]. This is a semi structured interview. Assessments are conducted on a six-point scale (0=not at all to 5=severe)with a total score range of 0-70. A score of >50 is considered to be a moderate-severe intensity. | 3 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Transcranial Magnetic Stimulation, Schizophrenia, Negative Symptoms