rTMS: A Treatment to Restore Function After Severe TBI

NCT02366754 | Unknown DMC

• 1 other identifier: CDMRP-PT130274
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 2

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.

Conditions

Traumatic Brain Injury

Keywords

Transcranial Magnetic Stimulation

Outcome Measures

Primary Outcomes (1)

• 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.

  Change from Baseline in DRS total score at an average 22 days

Secondary Outcomes (9)

• Disorders of Consciousness Scale-25

  Change from Baseline in DOCS-25 score at 7 days, 14 days, 21 days, 28 days and 50 days

• Coma Near Coma Scale

  Change from Baseline in CNC total score at an average 22 days

• Coma Recovery Scale-Revised

  Change from Baseline in CRS-R total score at an average 22 days

• Modified Tardieu Scale

  Change from Baseline in Modified Tardieu total score at an average 22 days

• Modified Ashworth Scale

  Change from Baseline in Modified Ashworth total score at an average 22 days

Study Arms (2)

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.

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.

Device: Placebo rTMS

Interventions

rTMS 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.

Active rTMS

Placebo rTMS 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.

Placebo rTMS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At study screening, persons have remained in states of Seriously Impaired Consciousness (SIC) for at least 3 and up to 24 months after TBI
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Edward Hines Jr. VA Hospital: lead
• Northwestern University: collaborator

Study Sites (2)

Northwestern University

Chicago, Illinois, 60141, United States

RECRUITING

Edward Hines, Jr. VA Hospital

Hines, Illinois, 60141, United States

RECRUITING

MeSH Terms

Conditions

Brain Injuries, Traumatic

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Study Officials

• Theresa Pape, DrPH, MA

  Edward Hines Jr. VA Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ann Guernon, MS

CONTACT

708-202-8387; ann.guernon@va.gov

Sandra Kletzel, PhD

CONTACT

708-202-5735; sandra.kletzel@va.gov

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Health Scientist

Study Record Dates

• First Submitted: January 26, 2015
• First Posted: February 19, 2015
• Study Start: February 1, 2016
• Primary Completion: February 1, 2020
• Study Completion: February 1, 2021
• Last Updated: September 6, 2019

Record last verified: 2019-09

Locations

US (2)