TMS in the Treatment of the Sequelae of Closed Brain Injury
Recruitment status was: Recruiting
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||The Use of Non Invasive Brain Stimulation in the Treatment of the Sequelae of Closed Brain Injury|
- Depression Symptom Severity [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
- Cognitive Tasks [ Time Frame: 4 Weeks ] [ Designated as safety issue: No ]
|Study Start Date:||October 2007|
|Estimated Study Completion Date:||December 2010|
|Estimated Primary Completion Date:||December 2009 (Final data collection date for primary outcome measure)|
|Active Comparator: 1||
|Placebo Comparator: 2||
Device: Sham rTMS
It is plausible to propose that the same treatment paradigm may result in an improvement in mood and cognition with the possibility that these changes will be self reinforcing resulting in enhanced quality of life and reduced service demands.
The proposal for the use of rTMS in the treatment of post TBI depression is also supported by aetiological models. In particular, rTMS would seem to have considerable potential to improve pathophysiological changes relevant to the treatment of post TBI depression and cognitive dysfunction. Early models of the mechanism of action of rTMS treatment in depression were based on the observation that rTMS is able to produce localised changes in cortical activity . The standard treatment paradigm generally has been found to produce an increase in local prefrontal cortical excitability. However, more recently there has been an increased understanding that rTMS modulates distal brain regions as well and potentially the strength of connections between brain regions. It has been proposed that its therapeutic effects in non TBI-related depression occur through modulation of dorsal frontal - subcortical limbic connectivity and potentially the actual integrity and strength of connections between these regions. If this is the case, altering cortical - cortical or cortical - subcortical connectivity may lead to therapeutic benefits in post TBI depression due to likely involvement of white matter changes in the development of TBI related mood disorder.
Aims/Objectives/Hypothesis/es Primary Aim: To assess the effectiveness of rTMS in treating depression post traumatic brain injury.
Secondary Aim: To gain preliminary data as to the possible effectiveness of rTMS in treating cognitive deficits post traumatic brain injury.
Hypothesis 1: Active bilateral sequential rTMS will lead to an improvement in the symptoms of post TBI depression, as measured by MADRS scores, when compared to sham treatment Hypothesis 2: Active bilateral sequential rTMS will lead to an improvement in cognitive executive functioning in individuals post TBI, when compared to sham treatment Hypothesis 3: Active bilateral sequential rTMS will lead to an improvement in life satisfaction and level of functioning in individuals post TBI, when compared to sham treatment.
Methodology Experimental Design and Randomisation Procedures The study has been designed to allow the reporting of results in a manner consistent with the international CONSORT guidelines. The study will involve a 4-week (20 session) randomized double-blind clinical trial with 2 treatment arms conducted at the Alfred Psychiatry Research Centre in Melbourne. Randomization will occur via the generation of a computer number sequence. Subjects will be randomized immediately prior to the commencement of the first treatment session, after the measurement of bilateral resting motor thresholds with standard means.
The main study phase (phase 1) will involve the 4 week randomized controlled trial conducted under strict double-blind conditions. Fidelity of the blinding process will be assessed at the end of this period with patients and raters. Phase 2 will involve the provision of open label treatment to patients who received sham treatment and wish to receive 'active' rTMS.
Responders to active treatment from phase 1 or 2 (defined as a 50% reduction in MADRS scores persisting for 1 week following the end of acute treatment) will enter phase 3, a 6 month maintenance phase. During this time, a single rTMS treatment session will be provided every week for 2 months and then every 2 weeks for 4 months. Acute treatment for up to 4 weeks will be reinstated if there is a persistent (2 week) increase in MADRS score of >25%.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00531258
|Alfred Psychiatry Research Centre|
|Prahran, Victoria, Australia, 3181|
|Principal Investigator:||Paul B Fitzgerald, MBBS, FRANZCP, PhD||Alfred Psychiatry Research Centre|