Clinical trial NCT02366754: rTMS: A Treatment to Restore Function After Severe TBI
Official title: rTMS: A Treatment to Restore Function After Severe TBI
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Traumatic Brain Injury
Keywords: Transcranial Magnetic Stimulation
Lead sponsor: Edward Hines Jr. VA Hospital
Sponsor class: FED
Collaborators: name: Northwestern University
First posted: 2015-02-19
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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). 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* 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

Primary outcomes:
measure: Disability Rating Scale
timeFrame: Change from Baseline in DRS total score at an average 22 days
Secondary outcomes:
measure: Disorders of Consciousness Scale-25
timeFrame: Change from Baseline in DOCS-25 score at 7 days, 14 days, 21 days, 28 days and 50 days
measure: Coma Near Coma Scale
timeFrame: Change from Baseline in CNC total score at an average 22 days
measure: Coma Recovery Scale-Revised
timeFrame: Change from Baseline in CRS-R total score at an average 22 days
measure: Modified Tardieu Scale
timeFrame: Change from Baseline in Modified Tardieu total score at an average 22 days
measure: Modified Ashworth Scale
timeFrame: Change from Baseline in Modified Ashworth total score at an average 22 days
measure: Spaulding Limb Movement Protocol
timeFrame: Change from Baseline in Spaudling Limb Movement total score at an average 22 days
measure: Consciousness Screening Algorithm
timeFrame: Change from Baseline in consciousness level at 7 days, 14 days, 21 days, 28 days and 50 days
measure: Functional Neuroimaging
timeFrame: Change from Baseline in amount of activation and connectivity at an average 22 days
measure: EEG Power Spectrum
timeFrame: Change Baseline in EEG frequency power at an average 22 days
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Hines
country: United States
facility: Edward Hines, Jr. VA Hospital
state: Illinois
Study officials:
affiliation: Edward Hines Jr. VA Hospital
name: Theresa Pape, DrPH, MA
role: PRINCIPAL_INVESTIGATOR
References: