Traumatic Brain InjuryNCT03523507
fMRI-neuronavigated rTMS Treatment for Symptoms of Depression Associated With Concussive TBI in the Military Population
A study testing Active: rTMS in people with Traumatic Brain Injury and Concussion, Mild, run by Henry M. Jackson Foundation for the Advancement of Military Medicine at 2 sites in United States.
Trial summary
This study aims to investigate the efficacy and tolerability of fMRI-targeted repetitive transcranial magnetic stimulation (rTMS) in the treatment of depressive symptoms in service members with a history of concussive traumatic brain injury (TBI). Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Traumatic Brain Injury, Concussion, Mild, Depressive Symptoms
- What is being tested?
- Active: rTMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Jul 2019to 27 Oct 2020
- 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 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age 18-64
- Current or former US military service member
- Eligible for care at DoD facilities
- Able to provide written, informed consent in English
- History of concussive TBI:
- >6 months prior to consent
Show all 9Show fewer
- Documented previously in medical records and/or as confirmed by the TBI Screener
- Must meet Criterion A of the DSM-5 criteria for Major Depressive Disorder as determined by a trained assessor
- Baseline MADRS >10
Who cannot join
- Elevated risk of seizures:
- Prior history of unprovoked seizures other than within 24 hours of concussive TBI
- Family history of seizures
- History of TBI resulting in penetrating trauma based on the TBI Screener
- Presence of intracranial tumor or intraparenchymal hemorrhage based on the structural MRI scan
- Heavy alcohol consumption within 48 hours, prior to any treatment session
Show all 24Show fewer
- Receiving tricyclic antidepressants or neuroleptics at doses that lower seizure threshold
- Contraindications to awake 3T MRI without contrast:
- Ferromagnetic implants or metallic shrapnel
- Severe claustrophobia
- Unable to lie awake, supine, stationary, with reasonable comfort in the scanner for approximately 45 minutes
- Markedly distorted functional brain anatomy such that rsfMRI targeting cannot be performed
- History of severe or recent uncontrolled heart disease
- Presence of a cardiac pacemaker or intracardiac lines
- Implanted neurostimulators and medication pumps
- Presence of rapidly progressive illnesses such as late stage cancer, neurodegenerative conditions, major organ failure, etc.
- History of Bipolar Disorder, Schizophrenia Spectrum Disorders, or Moderate/Severe Substance Use Disorders, with the exception of nicotine use disorders
- Increased risk of suicide as clinically evaluated
- Current evidence of substance-induced mood disorder, active psychosis, and/or depression secondary to general medical illness (other than TBI)
- Concomitant or previous history of receiving open-label TMS, other neurostimulatory treatment, or electroconvulsive therapy
- Pregnancy
- Female participants of childbearing potential must agree to use an effective method of birth control during the course of the study, or to remain abstinent from sex, to ensure they do not become pregnant during the course of the study
- Unilateral or bilateral upper extremity amputation or other condition precluding motor threshold calibration
- Any considerations that, in the opinion of the investigator, may adversely affect patient safety, participation, or the scientific validity of the data being collected (e.g., planned hospitalization halfway through the initial treatment period, limited life expectancy, etc.)
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889
Fort Belvoir Community Hospital
Fort Belvoir, Virginia, 22060
About this study
Official title: A Randomized, Sham-controlled, Double-blinded Study of Bilateral Prefrontal Individual Connectome-targeted Repetitive Transcranial Magnetic Stimulation to Treat the Symptoms of Depression Associated With Concussive Traumatic Brain Injury.
This study aims to investigate the efficacy and tolerability of fMRI-targeted repetitive transcranial magnetic stimulation (rTMS) in the treatment of depressive symptoms in service members with a history of concussive traumatic brain injury (TBI).
Up to ninety participants will be randomized to active or sham treatment. Participants randomized into the active group will receive 20 sessions of left-sided dorsolateral prefrontal cortex (DLFPC) high-frequency rTMS, followed by right-sided DLFPC low-frequency rTMS. The DLPFC treatment area will be identified by using individual subject-level resting state network estimation (Hacker et al., 2013). Participants randomized into the sham treatment group will receive 20 sham treatments designed to have similar sound and tactile sensation, without producing active treatment. Participants will also be asked to complete regular follow-up evaluations for up to a total of six follow-up sessions. Those who do not respond to the treatment will have the option to receive active treatment through this study regardless of group assignment to active or sham.
Read the detailed description
This study aims to investigate the efficacy and tolerability of individual connectome-targeted repetitive transcranial magnetic stimulation (ICT-rTMS) treatment to enhance the rehabilitation of service members with symptoms of depression and history of concussive traumatic brain injury (TBI).
This will be a multi-site, double-blinded, sham-controlled, prospective, randomized interventional trial. Up to ninety participants will be block randomized to active (ICT-rTMS) or sham treatment. Participants will receive 20 sessions of ICT-rTMS over approximately 5 weeks.
Resting-state functional magnetic resonance imaging (rsfMRI) and structural MRI will be obtained at baseline to allow for the calculation of connectome-targeted treatment coordinates and ensure the absence of structural abnormalities. The rsfMRI scan at baseline will also be used to establish the baseline for the secondary imaging outcome measures.
Treatment sessions will consist of high-frequency left dorsolateral prefrontal cortex (DLPFC) stimulation for 4,000 pulses followed by low-frequency right DLPFC stimulation for 1,000 pulses for a total stimulation time of approximately one hour per session. This protocol was chosen based on a recent meta-analysis (Brunoni et al., 2017) indicating that amongst the various treatment protocols, priming the low frequency right hemisphere stimulation with a high frequency left hemisphere stimulation led to the greatest efficacy for treatment of Major Depressive Episodes. Additionally, the overwhelming majority of the literature in TMS for depression targets the stimulation to DLPFC and the FDA has approved repetitive transcranial magnetic stimulation (rTMS) to DLPFC for the treatment of medication-resistant major depressive disorder (MDD).
The primary outcome will be change in depression severity from baseline to post-treatment. The primary analysis will be a comparison between the ICT-rTMS and sham groups. Secondary outcome measures utilized will include cognitive, quality of life, and emotional regulation measures, as well as imaging changes. Additional analyses will include durability of effects during the 6 months following treatment.
- Being tested
- Active: rTMS, Sham: rTMS
- Keywords
- Repetitive Transcranial Magnetic Stimulation, Military
- Medical subject headings
- Brain Injuries, Traumatic, Brain Concussion, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active: rTMSDevice
Daily sessions will consist of 3000 left-sided excitatory pulses at 10 Hz (with 4-second trains and 26-second inter-train interval) followed by 1000 right-sided inhibitory pulses at 1 Hz (in a single train). The DLPFC treatment target will be determined using individualized resting-state network mapping.
Sham: rTMSDevice
Daily sessions will consist of the same total number of sham pulses, designed to have similar sound and tactile sensation, without producing active stimulation.
| Study group | Role | What they receive |
|---|---|---|
| Active: rTMS | Experimental | Participants will receive 20 bilateral treatment sessions provided over approximately a 5-week period. Daily sessions entail approximately 60 minutes of time. Receives: Device: Active: rTMS |
| Sham: rTMS | Sham comparator | Sham: Repetitive Transcranial Magnetic Stimulation; Participants will receive sham treatment designed to have similar sound and tactile sensation, without producing active stimulation. Receives: Device: Sham: rTMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement in Depressive Symptoms
Compare change in overall Montgomery-Asberg Depression Rating Scale (MADRS) scores between participants randomized to ICT-rTMS and those randomized to blinded sham stimulation. The overall score ranges from 0 to 60 with a higher overall score indicating more severe depression.
Measured: Change between baseline, post-treatment (i.e., within 10 days of treatement completion), and 6-month follow-up
Secondary outcomes (7)
Changes in Cognitive Function
Assess changes in cognitive function and emotion processing as measured by the Automated Neuropsychological Assessment Metric (ANAM).
Measured: Change between baseline, post-treatment (i.e., within 10 days of treatement completion), and 6-month follow-up
Changes in TBI-related Symptoms
Assess changes in TBI-related symptoms as reflected by the TBI-QOL.
Measured: Change between baseline, post-treatment (i.e., within 10 days of treatement completion), and 6-month follow-up
Changes in PTSD-related Symptoms
Assess changes in PTSD-related symptoms as reflected by the PTSD Checklist for DSM-5 (PCL-5).
Measured: Change between baseline, post-treatment (i.e., within 10 days of treatement completion), and 6-month follow-up
Changes in Tinnitus-related Symptoms
To assess changes in tinnitus-related symptoms as reflected by the Mini Tinnitus Questionnaire (Mini TQ-12).
Measured: Change between baseline, post-treatment (i.e., within 10 days of treatement completion), and 6-month follow-up
Frequency of Adverse Effects
Compare the frequency and severity of adverse effects between those randomized to ICT-rTMS and those randomized to blinded sham stimulation.
Measured: Change between baseline, post-treatment (i.e., within 10 days of treatement completion), and 6-month follow-up
Changes in Psychotherapeutic Changes
Compare the number, dose, and/or type of adjunctive treatments undertaken by those randomized to ICT-rTMS as compared to those randomized to blinded sham stimulation.
Measured: Change between baseline, post-treatment (i.e., within 10 days of treatement completion), and 6-month follow-up
Changes in Resting-state fMRI
Assess changes in resting-state functional connectivity using functional magnetic resonance imaging (fMRI).
Measured: Change between baseline, post-treatment (i.e., within 10 days of treatement completion), and 6-month follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2018
- Study start1 Jul 2019
- Primary completion27 Oct 2020
- Study completion27 Oct 2020
Why it stopped: Study terminated due to COVID-19 restrictions
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Traumatic Brain InjuryStudies 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Henry M. Jackson Foundation for the Advancement of Military Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Center for Neuroscience and Regenerative Medicine (CNRM)
- Responsible party
- Sponsor
- Investigators
- David L Brody, MD, PhD, Principal investigator, Center for Neuroscience and Regenerative Medicine (CNRM)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03523507
- Sponsor's protocol ID
- 898115
- Status last verified
- Jul 2019
- First submitted
- 20 Dec 2017
- Last updated
- 3 Nov 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: Coded data will be deposited into the following repositories: the Center for Neuroscience and Regenerative Medicine (CNRM) Data Repository and the Federal Interagency Traumatic Brain Injury Research (FITBIR) Database.
Publications
Hacker CD, Laumann TO, Szrama NP, Baldassarre A, Snyder AZ, Leuthardt EC, Corbetta M. Resting state network estimation in individual subjects. Neuroimage. 2013 Nov 15;82:616-633. doi: 10.1016/j.neuroimage.2013.05.108. Epub 2013 Jun 2.
PubMed 23735260Brunoni AR, Chaimani A, Moffa AH, Razza LB, Gattaz WF, Daskalakis ZJ, Carvalho AF. Repetitive Transcranial Magnetic Stimulation for the Acute Treatment of Major Depressive Episodes: A Systematic Review With Network Meta-analysis. JAMA Psychiatry. 2017 Feb 1;74(2):143-152. doi: 10.1001/jamapsychiatry.2016.3644.
PubMed 28030740
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Sham-controlled, Double-blinded Study of Bilateral Prefrontal Individual Connectome-targeted Repetitive Transcranial Magnetic Stimulation to Treat the Symptoms of Depression Associated With Concussive Traumatic Brain Injury.
- ClinicalTrials.gov ID
- NCT03523507
- Acronym / sponsor ID
- 898115
- Keywords
- Repetitive Transcranial Magnetic Stimulation, Military
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study terminated due to COVID-19 restrictions
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Henry M. Jackson Foundation for the Advancement of Military MedicineUniversity, hospital or other
- Collaborators
- Center for Neuroscience and Regenerative Medicine (CNRM)
- Study start
- 1 Jul 2019 (actual)
- Primary completion
- 27 Oct 2020 (actual)
- Study completion
- 27 Oct 2020 (actual)
- First posted
- 14 May 2018 (actual)
- 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.
This study aims to investigate the efficacy and tolerability of fMRI-targeted repetitive transcranial magnetic stimulation (rTMS) in the treatment of depressive symptoms in service members with a history of concussive traumatic brain injury (TBI).
Up to ninety participants will be randomized to active or sham treatment. Participants randomized into the active group will receive 20 sessions of left-sided dorsolateral prefrontal cortex (DLFPC) high-frequency rTMS, followed by right-sided DLFPC low-frequency rTMS. The DLPFC treatment area will be identified by using individual subject-level resting state network estimation (Hacker et al., 2013). Participants randomized into the sham treatment group will receive 20 sham treatments designed to have similar sound and tactile sensation, without producing active treatment. Participants will also be asked to complete regular follow-up evaluations for up to a total of six follow-up sessions. Those who do not respond to the treatment will have the option to receive active treatment through this study regardless of group assignment to active or sham.
Detailed description
This study aims to investigate the efficacy and tolerability of individual connectome-targeted repetitive transcranial magnetic stimulation (ICT-rTMS) treatment to enhance the rehabilitation of service members with symptoms of depression and history of concussive traumatic brain injury (TBI).
This will be a multi-site, double-blinded, sham-controlled, prospective, randomized interventional trial. Up to ninety participants will be block randomized to active (ICT-rTMS) or sham treatment. Participants will receive 20 sessions of ICT-rTMS over approximately 5 weeks.
Resting-state functional magnetic resonance imaging (rsfMRI) and structural MRI will be obtained at baseline to allow for the calculation of connectome-targeted treatment coordinates and ensure the absence of structural abnormalities. The rsfMRI scan at baseline will also be used to establish the baseline for the secondary imaging outcome measures.
Treatment sessions will consist of high-frequency left dorsolateral prefrontal cortex (DLPFC) stimulation for 4,000 pulses followed by low-frequency right DLPFC stimulation for 1,000 pulses for a total stimulation time of approximately one hour per session. This protocol was chosen based on a recent meta-analysis (Brunoni et al., 2017) indicating that amongst the various treatment protocols, priming the low frequency right hemisphere stimulation with a high frequency left hemisphere stimulation led to the greatest efficacy for treatment of Major Depressive Episodes. Additionally, the overwhelming majority of the literature in TMS for depression targets the stimulation to DLPFC and the FDA has approved repetitive transcranial magnetic stimulation (rTMS) to DLPFC for the treatment of medication-resistant major depressive disorder (MDD).
The primary outcome will be change in depression severity from baseline to post-treatment. The primary analysis will be a comparison between the ICT-rTMS and sham groups. Secondary outcome measures utilized will include cognitive, quality of life, and emotional regulation measures, as well as imaging changes. Additional analyses will include durability of effects during the 6 months following treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active: rTMS | Experimental | Device: Active: rTMSParticipants will receive 20 bilateral treatment sessions provided over approximately a 5-week period. Daily sessions entail approximately 60 minutes of time. |
| Sham: rTMS | Sham comparator | Device: Sham: rTMSSham: Repetitive Transcranial Magnetic Stimulation; Participants will receive sham treatment designed to have similar sound and tactile sensation, without producing active stimulation. |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Age 18-64
- Current or former US military service member
- Eligible for care at DoD facilities
- Able to provide written, informed consent in English
- History of concussive TBI:
Key exclusion criteria (24 listed)
- Elevated risk of seizures:
- Contraindications to awake 3T MRI without contrast:
- History of severe or recent uncontrolled heart disease
- Presence of a cardiac pacemaker or intracardiac lines
- Implanted neurostimulators and medication pumps
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 |
|---|---|---|
| Active: rTMSDaily sessions will consist of 3000 left-sided excitatory pulses at 10 Hz (with 4-second trains and 26-second inter-train interval) followed by 1000 right-sided inhibitory pulses at 1 Hz (in a single train). The DLPFC treatment target will be determined using individualized resting-state network mapping. | Device | Active: rTMS |
| Sham: rTMSDaily sessions will consist of the same total number of sham pulses, designed to have similar sound and tactile sensation, without producing active stimulation. | Device | Sham: rTMS |
Primary outcome
Improvement in Depressive Symptoms
Time frame: Change between baseline, post-treatment (i.e., within 10 days of treatement completion), and 6-month follow-up
Compare change in overall Montgomery-Asberg Depression Rating Scale (MADRS) scores between participants randomized to ICT-rTMS and those randomized to blinded sham stimulation. The overall score ranges from 0 to 60 with a higher overall score indicating more severe depression.
7 secondary outcomes
Changes in Cognitive Function
Time frame: Change between baseline, post-treatment (i.e., within 10 days of treatement completion), and 6-month follow-up
Changes in TBI-related Symptoms
Time frame: Change between baseline, post-treatment (i.e., within 10 days of treatement completion), and 6-month follow-up
Changes in PTSD-related Symptoms
Time frame: Change between baseline, post-treatment (i.e., within 10 days of treatement completion), and 6-month follow-up
Changes in Tinnitus-related Symptoms
Time frame: Change between baseline, post-treatment (i.e., within 10 days of treatement completion), and 6-month follow-up
Frequency of Adverse Effects
Time frame: Change between baseline, post-treatment (i.e., within 10 days of treatement completion), and 6-month follow-up
Changes in Psychotherapeutic Changes
Time frame: Change between baseline, post-treatment (i.e., within 10 days of treatement completion), and 6-month follow-up
Changes in Resting-state fMRI
Time frame: Change between baseline, post-treatment (i.e., within 10 days of treatement completion), and 6-month follow-up
Results and safety
The study was stopped early (reason given: Study terminated due to COVID-19 restrictions). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2020.
- Background: PubMed 23735260Hacker CD, Laumann TO, Szrama NP, Baldassarre A, Snyder AZ, Leuthardt EC, Corbetta M. Resting state network estimation in individual subjects. Neuroimage. 2013 Nov 15;82:616-633. doi: 10.1016/j.neuroimage.2013.05.108. Epub 2013 Jun 2.
- Background: PubMed 28030740Brunoni AR, Chaimani A, Moffa AH, Razza LB, Gattaz WF, Daskalakis ZJ, Carvalho AF. Repetitive Transcranial Magnetic Stimulation for the Acute Treatment of Major Depressive Episodes: A Systematic Review With Network Meta-analysis. JAMA Psychiatry. 2017 Feb 1;74(2):143-152. doi: 10.1001/jamapsychiatry.2016.3644.
- Individual participant dataSharing planned: Yes. Coded data will be deposited into the following repositories: the Center for Neuroscience and Regenerative Medicine (CNRM) Data Repository and the Federal Interagency Traumatic Brain Injury Research (FITBIR) Database.
Related trials for Traumatic Brain Injury
Active, not recruitingObservational study
Transforming Research and Clinical Knowledge in Traumatic Brain Injury Epileptogenesis Project (TRACK-TBI EPI)
Traumatic Brain Injury, Post-traumatic Epilepsy
Enrolling by invitationPhase 1
Pilot Safety and Exploratory Efficacy of PSC-05 for the Treatment of Chronic Mild Traumatic Brain Injury
Mild Traumatic Brain Injury
RecruitingObservational study
Intracranial Pressure Monitoring in Moderate Traumatic Brain Injury
Moderate Traumatic Brain Injury
Not yet recruitingPhase 1
Nanopulse Laser Therapy
TBI (Traumatic Brain Injury)
RecruitingObservational study
Effect of Different Intravenous Fluids on Post-operative Chronic Subdural Hematoma Size and Recurrence
Chronic Subdural Hematoma
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.
David L Brody, MD, PhD principal investigator
Center for Neuroscience and Regenerative Medicine (CNRM)
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active: rTMS in people with Traumatic Brain Injury and Concussion, Mild, run by Henry M. Jackson Foundation for the Advancement of Military Medicine at 2 sites in United States.
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 9 inclusion and 24 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: stopped early, as of the sponsor's last update on 3 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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 was stopped early (reason given: Study terminated due to COVID-19 restrictions). Results are not available in the source record.
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?
Improvement in Depressive Symptoms (time frame: Change between baseline, post-treatment (i.e., within 10 days of treatement completion), and 6-month follow-up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03523507, which also lists 2 linked publications.
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 3 Nov 2020.