DepressionNCT00531258
TMS in the Treatment of the Sequelae of Closed Brain Injury
A study testing rTMS in people with Depression and Closed Head Injury, run by Bayside Health at 1 site in Australia.
Trial summary
Depression is very common in people who have experienced a traumatic brain injury. Few treatments have been found to be effective in treating depression in this situation. We intend to investigate the effectiveness of a form of brain stimulation, transcranial magnetic stimulation, which has been found to be effective… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Depression, Closed Head Injury
- What is being tested?
- rTMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 21 participants
- Where
- 1 siteAustralia
- Study dates
- Jan 2008to May 2015
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Use of Non Invasive Brain Stimulation in the Treatment of the Sequelae of Closed Brain Injury
Depression is very common in people who have experienced a traumatic brain injury. Few treatments have been found to be effective in treating depression in this situation. We intend to investigate the effectiveness of a form of brain stimulation, transcranial magnetic stimulation, which has been found to be effective in treating depression in people who have not undergone a brain injury. By evaluating new methods of treating depression in this population, we hope to increase the options available for treating people in this difficult situation. Furthermore, problems with aspects of thinking are also commonly present post brain injury, as in some individuals with depression. Various brain stimulation techniques, including transcranial magnetic stimulation (TMS) have been shown to have a positive effect on cognition. We also intend to investigate whether a therapeutic effect on cognitive deficits is present following TMS, in addition to any effects on depression. New treatment protocols will be developed, and understanding of the pathology and treatment of post traumatic brain injury depression will be enhanced.
Read the 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%.
- Conditions
- Depression, Closed Head Injury
- Being tested
- rTMS, Sham rTMS
- Keywords
- Depression, TBI, TMS, Major Depression resulting from a mild to moderate closed head injury
- Medical subject headings
- Depression, Head Injuries, Closed
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rTMSDevice
Bilateral rTMS
Sham rTMSDevice
sham rTMS
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Not described Receives: Device: rTMS |
| 2 | Placebo comparator | Not described Receives: Device: Sham rTMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Depression Symptom Severity
Measured: 4 weeks
Secondary outcomes (1)
Cognitive Tasks
Measured: 4 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2007 (estimated)
- Study startJan 2008
- Primary completionMay 2015
- Study completionMay 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DepressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bayside Health
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Paul B Fitzgerald, MBBS, FRANZCP, PhD, Principal investigator, Alfred Psychiatry Research Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00531258
- Sponsor's protocol ID
- 011007
- Status last verified
- Oct 2020
- First submitted
- 17 Sep 2007
- Last updated
- 14 Oct 2020
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Use of Non Invasive Brain Stimulation in the Treatment of the Sequelae of Closed Brain Injury
- ClinicalTrials.gov ID
- NCT00531258
- Acronym / sponsor ID
- 011007
- Conditions
- Depression, Closed Head Injury
- Keywords
- Depression, TBI, TMS, Major Depression resulting from a mild to moderate closed head injury
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Bayside HealthOther government
- Study start
- Jan 2008 (actual)
- Primary completion
- May 2015 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 18 Sep 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Depression is very common in people who have experienced a traumatic brain injury. Few treatments have been found to be effective in treating depression in this situation. We intend to investigate the effectiveness of a form of brain stimulation, transcranial magnetic stimulation, which has been found to be effective in treating depression in people who have not undergone a brain injury. By evaluating new methods of treating depression in this population, we hope to increase the options available for treating people in this difficult situation. Furthermore, problems with aspects of thinking are also commonly present post brain injury, as in some individuals with depression. Various brain stimulation techniques, including transcranial magnetic stimulation (TMS) have been shown to have a positive effect on cognition. We also intend to investigate whether a therapeutic effect on cognitive deficits is present following TMS, in addition to any effects on depression. New treatment protocols will be developed, and understanding of the pathology and treatment of post traumatic brain injury depression will be enhanced.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Device: rTMS |
| 2 | Placebo comparator | Device: Sham rTMS |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rTMSBilateral rTMS | Device | 1 |
| Sham rTMSsham rTMS | Device | 2 |
Primary outcome
Depression Symptom Severity
Time frame: 4 weeks
1 secondary outcome
Cognitive Tasks
Time frame: 4 Weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul B Fitzgerald, MBBS, FRANZCP, PhD principal investigator
Alfred Psychiatry Research Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing rTMS in people with Depression and Closed Head Injury, run by Bayside Health at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Depression Symptom Severity (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2020.