rTMS: A Treatment to Restore Function After Severe TBI

NCT ID: NCT02366754

Last Updated: 2019-09-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

58 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-02-29

Study Completion Date

2021-02-28

Brief Summary

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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

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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

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Traumatic Brain Injury

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Active rTMS

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.

Group Type EXPERIMENTAL

rTMS

Intervention Type DEVICE

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 rTMS

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.

Group Type SHAM_COMPARATOR

Placebo rTMS

Intervention Type DEVICE

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.

Interventions

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rTMS

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.

Intervention Type DEVICE

Placebo rTMS

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.

Intervention Type DEVICE

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Northwestern University

OTHER

Sponsor Role collaborator

Edward Hines Jr. VA Hospital

FED

Sponsor Role lead

Responsible Party

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Theresa Pape

Research Health Scientist

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Theresa Pape, DrPH, MA

Role: PRINCIPAL_INVESTIGATOR

Edward Hines Jr. VA Hospital

Locations

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Northwestern University

Chicago, Illinois, United States

Site Status RECRUITING

Edward Hines, Jr. VA Hospital

Hines, Illinois, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Ann Guernon, MS

Role: CONTACT

708-202-8387 ext. 23114

Sandra Kletzel, PhD

Role: CONTACT

708-202-5735

Facility Contacts

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Elyse Walsh, PT, DPT, NCS

Role: primary

708-968-0427

Ann Guernon, MS, CCC-SLP/L, CCRC

Role: backup

708-202-8387 ext. 23114

Theresa Pape, DrPH

Role: primary

708-202-4953

Elyse Walsh, PT, DPT, NCS

Role: backup

708-968-0427

Other Identifiers

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CDMRP-PT130274

Identifier Type: -

Identifier Source: org_study_id

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