- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00531258
TMS in the Treatment of the Sequelae of Closed Brain Injury
The Use of Non Invasive Brain Stimulation in the Treatment of the Sequelae of Closed Brain Injury
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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 [7]. 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%.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Victoria
-
Prahran, Victoria, Australia, 3181
- Alfred Psychiatry Research Centre
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion criteria:
- Be aged 18-60 and have capacity to consent
- Currently meet DSM-IV criteria for a diagnosis of major depressive disorder (expect for the exclusion of causality by a general medical condition referring to the TBI) and have the persistence of depressive symptoms for at least one month at sufficient severity to warrant the diagnosis.
- Have experienced a closed head injury of mild to moderate severity (Glasgow coma scale score (GCS) of greater than 8), preceding their depression, and are at least 3 months post injury. The injury must not have involved specific direct damage to either frontal lobe.
- Have a Montgomery Asberg Rating Scale Score of > 20 (moderate - severe depression). Including only a more severely ill group of subjects limits the placebo response rate.
- Have had no increase or initiation of new antidepressant (or other psychoactive) therapy in the 4 weeks prior to enrolment.
Exclusion Criteria:
- Patients who have an unstable medical condition, neurological disorder or any history of a seizure disorder or are currently pregnant or lactating.
- Patients who have experienced clear structural damage to the left or right dorsolateral prefrontal cortex as documented on MRI scan
- Have a current DSM IV diagnosis of alcohol or substance dependence disorder.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: 2
|
sham rTMS
|
Active Comparator: 1
|
Bilateral rTMS
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Depression Symptom Severity
Time Frame: 4 weeks
|
4 weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Cognitive Tasks
Time Frame: 4 Weeks
|
4 Weeks
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Paul B Fitzgerald, MBBS, FRANZCP, PhD, Alfred Psychiatry Research Centre
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 011007
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Depression
-
ProgenaBiomeRecruitingDepression | Depression, Postpartum | Depression, Anxiety | Depression Moderate | Depression Severe | Clinical Depression | Depression in Remission | Depression, Endogenous | Depression ChronicUnited States
-
Washington University School of MedicineCompletedTreatment Resistant Depression | Late Life Depression | Geriatric Depression | Refractory Depression | Therapy-Resistant DepressionUnited States, Canada
-
University of California, San FranciscoRecruitingDepression Moderate | Depression Mild | Depression, TeenUnited States
-
University GhentUniversiteit Antwerpen; Janssen-Cilag Ltd.RecruitingDepression Moderate | Depression Severe | Depression MildBelgium
-
Baylor College of MedicineUniversity of TexasRecruitingDepression | Depression Moderate | Depression Severe | Suicide and Self-harm | Depression in Adolescence | Depression MildUnited States
-
University of Cape TownNational Institute of Mental Health (NIMH)CompletedPostpartum Depression | Clinical Depression | Moderate DepressionSouth Africa
-
Washington University School of MedicinePatient-Centered Outcomes Research Institute; National Institute of Mental...CompletedMajor Depressive Disorder | Treatment Resistant Depression | Treatment-Refractory Depression | Late Life Depression | Geriatric DepressionUnited States, Canada
-
Northern Illinois UniversityUniversity Autonoma de Santo DomingoTerminatedDepression Moderate | Depression MildUnited States, Dominican Republic
-
Gerbera Therapeutics, Inc.Not yet recruitingPostpartum Depression | Depression, Postpartum | Postnatal Depression | Post-partum Depression | Post-Natal DepressionUnited States
-
Lawson Health Research InstituteTerminated
Clinical Trials on rTMS
-
Chang Gung Memorial HospitalMinistry of Science and Technology, TaiwanRecruiting
-
Chang Gung Memorial HospitalRecruiting
-
Centre Hospitalier Universitaire de Saint EtienneCompleted
-
Centre hospitalier de Ville-Evrard, FranceRecruitingTo Evaluate the Effectiveness of Open rTMSFrance
-
Changping LaboratoryBeijing HuiLongGuan HospitalRecruitingMajor Depressive Disorder | Severe Depression | Moderate DepressionChina
-
Centre Hospitalier Universitaire de Saint EtienneCompleted
-
Stanford UniversityRecruitingMajor Depressive DisorderUnited States
-
Bayside HealthCompletedAutistic Disorder | Asperger's DisorderAustralia
-
Changping LaboratoryWuhan Mental Health CentreRecruitingMajor Depressive Disorder | Severe Depression | Moderate DepressionChina
-
Assiut UniversityCompletedObsessive Compulsive Disorders