Traumatic Brain InjuryNCT02366754
rTMS: A Treatment to Restore Function After Severe TBI
A study testing rTMS in people with Traumatic Brain Injury, run by Edward Hines Jr. VA Hospital at 2 sites in United States.
Trial summary
The purpose of this study is to address the need for targeted treatments that induce functional and structural changes in the brain, ultimately improving neurobehavioral functioning, the investigators propose examining the therapeutic effectiveness of repetitive Transcranial Magnetic Stimulation (rTMS). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Traumatic Brain 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
- 58 participants
- Where
- 2 sitesUnited States
- Study dates
- Feb 2016to Feb 2021
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- At study screening, persons have remained in states of Seriously Impaired Consciousness (SIC) for at least 3 and up to 24 months after TBI
- 18 years of age or older
- Traumatic Brain Injury etiology
- Able to participate in all phases of study including follow-up re-admission
- Able to identify legally authorized representative/surrogate who is able to read and understand informed consent document and provide written consent
Who cannot join
- Primary injury is a non-traumatic brain injury (and is not secondary to TBI) (e.g., inflammatory, infectious, toxic and metabolic encephalopathies, anoxia, cancer, ischemic and hemorrhagic stroke)
- History of TBI, psychiatric illness (DSM criteria) and or organic brain syndrome (e.g. Alzheimer's)
- Left dorsal lateral pre-frontal cortex (DLPFC) is not accessible (e.g., left frontal lobectomy)
- Incurred large cortically based ischemic infarction subsequent to TBI (size is determined collectively by neurosurgeon, neurologist, neuroradiologist and principal investigator)
- At study screening, patient is receiving anti-epileptic medications to control active seizures
- Have had a documented seizure within 3 months of study screening
Show all 14Show fewer
- Are ventilator dependent at time of study screening
- Have recovered full consciousness at time of study screening as indicated by a Motor Function scale score of 6 and/or a Communication scale score of 2 on the CRS-R
- Receiving central nervous system (CNS) stimulants that cannot be safely discontinued via titration
- Patient did not speak English prior to injury (bedside testing is conducted in English)
- Pregnant
- Have implanted cardiac pacemaker or defibrillator, cochlear implant or nerve stimulator
- Have MRI or TMS contraindications such as pre-injury claustrophobia, metal in eyes/face or brain
- Other medical conditions, that in investigator's opinion, would preclude subject from completing study
Trial locations and contacts
2 sites in 1 country.
United States2 sites, 2 recruiting
- Recruiting
Northwestern University
Chicago, Illinois, 60141
Elyse Walsh, PT, DPT, NCS, 708-968-0427, Elyse.Walsh@va.gov
Ann Guernon, MS, CCC-SLP/L, CCRC, 708-202-8387 ext. 23114, Ann.Guernon@va.gov
- Recruiting
Edward Hines, Jr. VA Hospital
Hines, Illinois, 60141
Theresa Pape, DrPH, 708-202-4953, Theresa.BenderPape@va.gov
Elyse Walsh, PT, DPT, NCS, 708-968-0427, Elyse.Walsh@va.gov
About this study
The purpose of this study is to address the need for targeted treatments that induce functional and structural changes in the brain, ultimately improving neurobehavioral functioning, the investigators propose examining the therapeutic effectiveness of repetitive Transcranial Magnetic Stimulation (rTMS). The objective is to improve functional recovery for persons remaining in vegetative (VS) and minimally conscious (MCS) states 3 to 24 months after severe TBI. The approach is to determine the neurobehavioral effect of rTMS, the relationship between neurobehavioral changes and net neural effects, and to identify and define the neural mechanisms related to neurobehavioral improvements by providing 30 active or placebo rTMS sessions.
Read the detailed description
The specific aims (SA) of the CDMRP study are:
SA-1: To determine presence, direction and sustainability of rTMS induced neurobehavioral effects using the DRS (lower scores indicate more function).
SA-2: To determine presence, direction and sustainability of rTMS-induced changes in functional neural activation and whether these changes correlate with improving neurobehavioral function.
SA-3: To determine the rTMS effect on white fiber tracts and whether rTMS-related effects correlate with neurobehavioral gains. White fiber tracts will be examined according to changes in Fractional Anisotropy (FA), Mean Diffusivity (MD), Radial Diffusivity (RD), and Axial Diffusivity (AD).
SA-4: To confirm rTMS safety for severe TBI. The investigators hypothesize that there will be no difference between active and placebo groups according to average number of research related adverse events (AE) during treatment.
To accomplish these aims, the investigators will conduct a double blind, randomized, placebo controlled clinical trial where 58 persons remaining in states of disordered consciousness for 3 to 24 months after TBI are randomized to the active rTMS group or the placebo rTMS group.
The primary outcome is neurobehavioral recovery slope as measured by the total Disability Rating Scale (DRS), which will be collected at bedside at Baseline, Midpoint (15th rTMS Session) and Endpoint (30th rTMS Session). The DRS-PI will be collected weekly via telephone interview for the three weeks between Endpoint and Follow up (3 weeks after 30th rTMS session). Secondary outcomes include four measures of functional neural activation: task related functional magnetic resonance imaging (fMRI), functional connectivity MRI (fcMRI), EEG-Rest and EEG-Task. The functional neural activation measures will be collected at baseline, endpoint and follow up. Motor Threshold Testing and Neurobehavioral measures in addition to the DRS and physical measures will also be collected as secondary outcomes. Motor Threshold testing, neurobehavioral and physical measures will be collected at baseline, midpoint, endpoint and follow up. The additional Neurobehavioral and physical measures are the Disorders of Consciousness Scale-25 (DOCS-25), Coma Recovery Scale Revised (CRS-R), Coma Near Coma Scale (CNC), Modified Tardieu Scale, Modified Ashworth Scale, Spaulding Limb Movement Protocol and the Consciousness Screening Algorithm.
- Conditions
- Traumatic Brain Injury
- Being tested
- rTMS, Placebo rTMS
- Keywords
- Transcranial Magnetic Stimulation
- Medical subject headings
- Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rTMSDevice
Repetitive TMS is a non-invasive neural stimulation technique achieved via electromagnetic induction. An insulated metal coil is placed on the scalp and short discharges of electric current are directed through the coil producing a magnetic field. This magnetic field is accompanied by an electric field that passes through the skull inducing currents in the tissue beneath the coil. If a cell beneath the coil is viable, then rTMS initiates or inhibits an action potential affecting ongoing neural activity. 30 sessions of active rTMS are provided.
Placebo rTMSDevice
The placebo coil simulates magnetic stimulation, but does not actually emit a pulse. The placebo coil looks, sounds and feels like an active rTMS coil. The placebo coil, visually identical to the active coil, provides a slight sensory sensation and discharge noise (i.e., clicking) nearly identical to that of the active coil.
| Study group | Role | What they receive |
|---|---|---|
| Active rTMS | Experimental | The intervention consists of 30 active rTMS sessions. Each session is comprised of 300 trains of paired pulses with the following parameters: 100µs paired pulses separated by 100ms inter-pulse-intervals and a five second inter-train-interval. Pulse intensity will be set at 110% of each participant's motor threshold. Active rTMS sessions will be provided two times per day with a 70mm figure-of-eight coil over the left dorsolateral prefrontal cortex. Two Magstim-2002 units and a Bistim2 module will be used to administer active rTMS. Participants assigned to the active rTMS group will receive a total of 1.8 seconds of stimulation. Active rTMS will be administered 2 times daily with the following weekly schedule: 2 days of rTMS, 1 day of rest, 2 days of rTMS, 2 days of rest. Receives: Device: rTMS |
| Placebo rTMS | Sham comparator | The intervention consists of 30 placebo rTMS sessions. Each session is comprised of 300 paired-pulse trains with the following parameters: 100µs paired pulses separated by 100ms inter-pulse-intervals and a five second inter-train-interval. Placebo rTMS sessions will be provided two times per day with a 70mm figure-of-eight coil over the left DLPFC. Two Magstim-2002 units and a Bistim2 module will be used to administer placebo rTMS. The placebo coil simulates magnetic stimulation, but does not actually emit a pulse. Participants assigned to the placebo rTMS group will receive 0 seconds of stimulation. Placebo rTMS will be administered with the following weekly schedule: 2 days of rTMS, 1 day of rest, 2 days of rTMS, 2 days of rest. Receives: Device: Placebo rTMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disability Rating Scale
The DRS consists of 8 items that address: arousability, awareness and responsivity; cognitive ability for self-care; dependence on others; and psychosocial adaptability. Scores on the DRS range from 0 to 29 with higher scores indicating greater levels of disability.
Measured: Change from Baseline in DRS total score at an average 22 days
Secondary outcomes (9)
Disorders of Consciousness Scale-25
Neurobehavioral measure that evaluates the subject's responses to sounds, touch, objects, people, tastes, movements and smells
Measured: Change from Baseline in DOCS-25 score at 7 days, 14 days, 21 days, 28 days and 50 days
Coma Near Coma Scale
Neurobehavioral measure that evaluates the subject's responses to sounds, touch, objects, people, tastes, movements and smells
Measured: Change from Baseline in CNC total score at an average 22 days
Coma Recovery Scale-Revised
Neurobehavioral measure that evaluates the subject's responses to sounds, touch, objects, people, tastes, movements and smells
Measured: Change from Baseline in CRS-R total score at an average 22 days
Modified Tardieu Scale
Spasticity measure for the following muscles: shoulder flexion, elbow flexion/extension, wrist flexion/extension, hip flexion/extension, knee flexion/extension and ankle extension. The scoring is based on 3 velocities of movement where the higher the rating, the higher degree of muscle tone.
Measured: Change from Baseline in Modified Tardieu total score at an average 22 days
Modified Ashworth Scale
Spasticity measure for the following muscles: shoulder flexion, elbow flexion/extension, wrist flexion/extension, hip flexion/extension, knee flexion/extension and ankle extension. The individual muscle scores will be compared between time points. The higher the rating on the Modified Ashworth the greater degree of muscle tone demonstrated during testing.
Measured: Change from Baseline in Modified Ashworth total score at an average 22 days
Spaulding Limb Movement Protocol
Measures limb movement in response to execution of motor commands in response to 1-step commands that engage upper extremity movements with and without object use.
Measured: Change from Baseline in Spaudling Limb Movement total score at an average 22 days
Consciousness Screening Algorithm
Measured: Change from Baseline in consciousness level at 7 days, 14 days, 21 days, 28 days and 50 days
Functional Neuroimaging
Activation in response to a task, resting state and diffusion tensor imaging
Measured: Change from Baseline in amount of activation and connectivity at an average 22 days
EEG Power Spectrum
Measured: Change Baseline in EEG frequency power at an average 22 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2015 (estimated)
- Study startFeb 2016
- Primary completionFeb 2020 (estimated)
- Study completionFeb 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- 58 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Edward Hines Jr. VA Hospital
- Sponsor type
- US federal agency
- Collaborators
- Northwestern University
- Responsible party
- Principal investigator, Theresa Pape, Edward Hines Jr. VA Hospital
- Investigators
- Theresa Pape, DrPH, MA, Principal investigator, Edward Hines Jr. VA Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02366754
- Sponsor's protocol ID
- CDMRP-PT130274
- Status last verified
- Sep 2019
- First submitted
- 26 Jan 2015
- Last updated
- 6 Sep 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- rTMS: A Treatment to Restore Function After Severe TBI
- ClinicalTrials.gov ID
- NCT02366754
- Acronym / sponsor ID
- CDMRP-PT130274
- Conditions
- Traumatic Brain Injury
- Keywords
- Transcranial Magnetic Stimulation
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 58 participants (estimated)
- Lead sponsor
- Edward Hines Jr. VA HospitalUS federal agency
- Collaborators
- Northwestern University
- Study start
- Feb 2016 (actual)
- Primary completion
- Feb 2020 (estimated)
- Study completion
- Feb 2021 (estimated)
- First posted
- 19 Feb 2015 (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.
The purpose of this study is to address the need for targeted treatments that induce functional and structural changes in the brain, ultimately improving neurobehavioral functioning, the investigators propose examining the therapeutic effectiveness of repetitive Transcranial Magnetic Stimulation (rTMS). The objective is to improve functional recovery for persons remaining in vegetative (VS) and minimally conscious (MCS) states 3 to 24 months after severe TBI. The approach is to determine the neurobehavioral effect of rTMS, the relationship between neurobehavioral changes and net neural effects, and to identify and define the neural mechanisms related to neurobehavioral improvements by providing 30 active or placebo rTMS sessions.
Detailed description
The specific aims (SA) of the CDMRP study are:
SA-1: To determine presence, direction and sustainability of rTMS induced neurobehavioral effects using the DRS (lower scores indicate more function).
SA-2: To determine presence, direction and sustainability of rTMS-induced changes in functional neural activation and whether these changes correlate with improving neurobehavioral function.
SA-3: To determine the rTMS effect on white fiber tracts and whether rTMS-related effects correlate with neurobehavioral gains. White fiber tracts will be examined according to changes in Fractional Anisotropy (FA), Mean Diffusivity (MD), Radial Diffusivity (RD), and Axial Diffusivity (AD).
SA-4: To confirm rTMS safety for severe TBI. The investigators hypothesize that there will be no difference between active and placebo groups according to average number of research related adverse events (AE) during treatment.
To accomplish these aims, the investigators will conduct a double blind, randomized, placebo controlled clinical trial where 58 persons remaining in states of disordered consciousness for 3 to 24 months after TBI are randomized to the active rTMS group or the placebo rTMS group.
The primary outcome is neurobehavioral recovery slope as measured by the total Disability Rating Scale (DRS), which will be collected at bedside at Baseline, Midpoint (15th rTMS Session) and Endpoint (30th rTMS Session). The DRS-PI will be collected weekly via telephone interview for the three weeks between Endpoint and Follow up (3 weeks after 30th rTMS session). Secondary outcomes include four measures of functional neural activation: task related functional magnetic resonance imaging (fMRI), functional connectivity MRI (fcMRI), EEG-Rest and EEG-Task. The functional neural activation measures will be collected at baseline, endpoint and follow up. Motor Threshold Testing and Neurobehavioral measures in addition to the DRS and physical measures will also be collected as secondary outcomes. Motor Threshold testing, neurobehavioral and physical measures will be collected at baseline, midpoint, endpoint and follow up. The additional Neurobehavioral and physical measures are the Disorders of Consciousness Scale-25 (DOCS-25), Coma Recovery Scale Revised (CRS-R), Coma Near Coma Scale (CNC), Modified Tardieu Scale, Modified Ashworth Scale, Spaulding Limb Movement Protocol and the Consciousness Screening Algorithm.
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: rTMSThe intervention consists of 30 active rTMS sessions. Each session is comprised of 300 trains of paired pulses with the following parameters: 100µs paired pulses separated by 100ms inter-pulse-intervals and a five second inter-train-interval. Pulse intensity will be set at 110% of each participant's motor threshold. Active rTMS sessions will be provided two times per day with a 70mm figure-of-eight coil over the left dorsolateral prefrontal cortex. Two Magstim-2002 units and a Bistim2 module will be used to administer active rTMS. Participants assigned to the active rTMS group will receive a total of 1.8 seconds of stimulation. Active rTMS will be administered 2 times daily with the following weekly schedule: 2 days of rTMS, 1 day of rest, 2 days of rTMS, 2 days of rest. |
| Placebo rTMS | Sham comparator | Device: Placebo rTMSThe intervention consists of 30 placebo rTMS sessions. Each session is comprised of 300 paired-pulse trains with the following parameters: 100µs paired pulses separated by 100ms inter-pulse-intervals and a five second inter-train-interval. Placebo rTMS sessions will be provided two times per day with a 70mm figure-of-eight coil over the left DLPFC. Two Magstim-2002 units and a Bistim2 module will be used to administer placebo rTMS. The placebo coil simulates magnetic stimulation, but does not actually emit a pulse. Participants assigned to the placebo rTMS group will receive 0 seconds of stimulation. Placebo rTMS will be administered with the following weekly schedule: 2 days of rTMS, 1 day of rest, 2 days of rTMS, 2 days of rest. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- At study screening, persons have remained in states of Seriously Impaired Consciousness (SIC) for at least 3 and up to 24 months after TBI
- 18 years of age or older
- Traumatic Brain Injury etiology
- Able to participate in all phases of study including follow-up re-admission
- Able to identify legally authorized representative/surrogate who is able to read and understand informed consent document and provide written consent
Key exclusion criteria (14 listed)
- Primary injury is a non-traumatic brain injury (and is not secondary to TBI) (e.g., inflammatory, infectious, toxic and metabolic encephalopathies, anoxia, cancer, ischemic and hemorrhagic stroke)
- History of TBI, psychiatric illness (DSM criteria) and or organic brain syndrome (e.g. Alzheimer's)
- Left dorsal lateral pre-frontal cortex (DLPFC) is not accessible (e.g., left frontal lobectomy)
- Incurred large cortically based ischemic infarction subsequent to TBI (size is determined collectively by neurosurgeon, neurologist, neuroradiologist and principal investigator)
- At study screening, patient is receiving anti-epileptic medications to control active seizures
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 |
|---|---|---|
| rTMSRepetitive TMS is a non-invasive neural stimulation technique achieved via electromagnetic induction. An insulated metal coil is placed on the scalp and short discharges of electric current are directed through the coil producing a magnetic field. This magnetic field is accompanied by an electric field that passes through the skull inducing currents in the tissue beneath the coil. If a cell beneath the coil is viable, then rTMS initiates or inhibits an action potential affecting ongoing neural activity. 30 sessions of active rTMS are provided. | Device | Active rTMS |
| Placebo rTMSThe placebo coil simulates magnetic stimulation, but does not actually emit a pulse. The placebo coil looks, sounds and feels like an active rTMS coil. The placebo coil, visually identical to the active coil, provides a slight sensory sensation and discharge noise (i.e., clicking) nearly identical to that of the active coil. | Device | Placebo rTMS |
Primary outcome
Disability Rating Scale
Time frame: Change from Baseline in DRS total score at an average 22 days
The DRS consists of 8 items that address: arousability, awareness and responsivity; cognitive ability for self-care; dependence on others; and psychosocial adaptability. Scores on the DRS range from 0 to 29 with higher scores indicating greater levels of disability.
9 secondary outcomes
Disorders of Consciousness Scale-25
Time frame: Change from Baseline in DOCS-25 score at 7 days, 14 days, 21 days, 28 days and 50 days
Coma Near Coma Scale
Time frame: Change from Baseline in CNC total score at an average 22 days
Coma Recovery Scale-Revised
Time frame: Change from Baseline in CRS-R total score at an average 22 days
Modified Tardieu Scale
Time frame: Change from Baseline in Modified Tardieu total score at an average 22 days
Modified Ashworth Scale
Time frame: Change from Baseline in Modified Ashworth total score at an average 22 days
Spaulding Limb Movement Protocol
Time frame: Change from Baseline in Spaudling Limb Movement total score at an average 22 days
Consciousness Screening Algorithm
Time frame: Change from Baseline in consciousness level at 7 days, 14 days, 21 days, 28 days and 50 days
Functional Neuroimaging
Time frame: Change from Baseline in amount of activation and connectivity at an average 22 days
EEG Power Spectrum
Time frame: Change Baseline in EEG frequency power at an average 22 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Sep 2019.
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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.
Theresa Pape, DrPH, MA principal investigator
Edward Hines Jr. VA Hospital
2 sites 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 Traumatic Brain Injury, run by Edward Hines Jr. VA Hospital 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 5 inclusion and 14 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: status not confirmed, as of the sponsor's last update on 6 Sep 2019. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ann Guernon, MS (708-202-8387 ext. 23114, ann.guernon@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disability Rating Scale (time frame: Change from Baseline in DRS total score at an average 22 days). 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 6 Sep 2019.