Rehabilitation Center

Clinical Trials

Repetitive Transcranial Magnetic Stimulation

An Experimental Treatment to Restore Function after Severe TBI

The purpose of this study is to address the need for targeted treatments that induce functional and structural changes in the brain to ultimately improve neurobehavioral functioning by examining the therapeutic effectiveness of repetitive Transcranial Magnetic Stimu-lation (rTMS). The rTMS protocol employed in the clinical trial is based on pilot data collected from 3 participants. Despite poor recovery likelihood, all three pilot participants made neurobehavioral gains during rTMS and each maintained these gains at follow-up. Although an incidence of seizure activity was apparent in one pilot subject, the safety data from the pilot subjects largely confirms a lack of adverse events related to rTMS (see rTMS Safety section for more details).

This project has IRB approval at the Santa Clara Valley Medical Center, and is funded by the Department of Defense and the Joint Warfighter Program. The study sponsor is Dr. Theresa Pape, with the Edward Hines Jr. VA Hospital. This study is simultaneously taking place at Northwestern University, the Edward Hines Jr. VA Hospital, and the Santa Clara Valley Medical Center. For further information on the study, its locations, and the sponsors and collaborators, please visit:
https://clinicaltrials.gov/ct2/show/NCT02366754?term=NCT02366754&rank=1

The study is a double-blind, randomized, placebo-controlled trial, lasting 10 weeks:
Week 1: Baseline Measures
Weeks 2-5: rTMS Intervention (30 active or placebo rTMS sessions)
Week 6: Endpoint Measurement/Discharge
Weeks 6-9: Weekly Safety Follow-up
Week 10: Final Endpoint Measurement

rTMS BACKGROUND
 

Repetitive TMS is a non-invasive and versatile neural stimulation technique achieved via electromagnetic induction. An insulated met-al 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. rTMS can be used to induce and modulate neural activity throughout the brain and within disconnected neural networks for these heterogeneous injuries.

Inclusion Criteria

Exclusion 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

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)

18 years of age or older

History of TBI, psychiatric illness (DSM criteria) and or organic brain syndrome (e.g. Alzheimer’s)

Traumatic Brain Injury etiology

Left dorsal lateral pre-frontal cortex (DLPFC) is not accessible (e.g., left frontal lobectomy)

Able to participate in all phases of study including fol-low-up re-admission

Incurred large cortically based ischemic infarction sub-sequent to TBI (size is determined collectively by neu-rosurgeon, neurologist, neuroradiologist and principal investigator)

Able to identify legally authorized representative/surrogate who is able to read and understand informed consent document and provide written consent

At study screening, patient is receiving anti-epileptic medications to control active seizures

≥ 110 pounds if participating in the blood sample study

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 CNS stimulants that cannot be safely dis-continued 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

rTMS SAFETY:

The safety data we collected with our three pilot participants largely confirms the lack of adverse events attributable to rTMS when used one time per day; however, one participant did have one seizure. Seizures are a known risk for rTMS in healthy persons and for persons with neurological conditions with the risk of inducing seizures in persons with neurological disorders thought to be < 1%. In our pilot study, after the seizure stopped without intervention, this participant safely tolerated a reduced dose of 19 more rTMS sessions while on Keppra. While Participant # 2 did not have any seizures, he was receiving Keppra during all rTMS sessions at the full dose. These find-ings indicate that the risk of seizures with this patient population is really unknown and it is important that we optimize each patient’s safety by admitting them to an acute bed during provision of rTMS sessions. We propose providing rTMS two times per day rather than one time per day because this will optimize feasibility when implemented in the future during daily medical rehabilitation.

The literature and our evidence suggest that some patients may incur rTMS related seizures, but that when seizures do occur the patients will likely be able to tolerate continuing with rTMS on a reduced dose and while receiving seizure prophylaxis. To inform future implementation of rTMS as a treatment, it is also important that we study safety in our proposed study. Given the paucity of safety trials of TMS with TBI and our findings with our three pilot participants, our fourth specific aim addresses the need to comprehensively evaluate safety of rTMS with severe TBI.

Stopping Neurostimulants: There are no known risks to weaning people off of medications thought to stimulate brain activity and that are referred to as neurostimulants. However, one study participant experienced increased congestion and secretions after being weaned off of a neurostimulant called Amantadine. This may have been related to the removal of Amantadine as required for participation in this study. If you were weaned from a neurostimulant you will be monitored for changes in respiratory status as part of the standard medical care provided dur-ing study participation. Any changes in respiratory symptoms will be monitored by the attend-ing physician for this study.

About Us

 

If you are interested in referring patients, need additional information​, or wish to refer us to other organizations or colleagues, please feel free to contact:

Dr. Thao Duong
Vice Chair,
Department of Physical Medicine & Rehabilitation, Brain Injury Medicine
Santa Clara Valley Medical Center
[email protected]
408-885-2100

Or

Mr. Ben Dirlikov
Interim Director,
Rehabilitation Research Center
Santa Clara Valley Medical Center
[email protected]
408-781-8175

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