Overview

This trial is active, not recruiting.

Condition traumatic brain injury
Treatments rtms, amantadine
Sponsor Edward Hines Jr. VA Hospital
Start date February 2014
End date August 2016
Trial size 4 participants
Trial identifier NCT02025439, 1R21HD075192

Summary

The purpose of this study is to examine the safety and efficacy of repetitive transcranial magnetic stimulation (rTMS) combined with Amantadine relative to rTMS Alone and Amantadine Alone for persons in chronic states of seriously impaired consciousness. The hypothesis is that provision of rTMS+Amantadine will provide a safe yet synergistic effect that induces or accelerates functional recovery.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model factorial assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Active Comparator)
Subjects assigned to rTMS Alone will receive 30 sessions of rTMS. Two rTMS sessions will be provided per day, four days per week.
rtms Repetitive Transcranial Magnetic Stimulation
(Active Comparator)
Subjects who are assigned to the Amantadine Alone group will receive 28 doses of Amantadine (100mg BID) every day for 28 days.
amantadine Symadine
(Active Comparator)
All subjects, after first completing Amantadine Alone arm or rTMS Alone arm, will receive rTMS plus Amantadine. A total of 30 rTMS sessions are provided, 2 rTMS sessions per day, four days per week, while receiving 200mg of Amantadine daily.
rtms Repetitive Transcranial Magnetic Stimulation
amantadine Symadine

Primary Outcomes

Measure
Safety
time frame: Daily for 7 weeks

Secondary Outcomes

Measure
Disorders of Consciousness Scale (DOCS) Neurobehavioral Growth Trajectories
time frame: Change from baseline measured weekly for 7 weeks
Change from Baseline in Functional magnetic resonance imaging (fMRI)
time frame: Change from baseline fMRI measured at 3 weeks and 6 weeks

Eligibility Criteria

Male or female participants from 18 years up to 64 years old.

Inclusion Criteria: - 18-64 years of age - Suffered a severe brain injury of traumatic origin at least 1-year prior to study enrollment - Remain in a state of disordered consciousness - Brain injuries will include injury with resulting coup-contre-coup injuries, excluding persons with trauma due to blunt injuries and/or non-traumatic encephalopathy Exclusion Criteria: - Have 1 or more Amantadine contraindications: On monoamino oxidase inhibitor-B, hypersensitivity/idiosyncrasy to sympathomimetic amines, uncontrolled hypertension, glaucoma or Congestive Heart Failure - Have contraindications to Amantadine Dose of 200 mg Daily as determined by estimated Glomerular Filtration Rate (eGFR) ≤ 60 (ml/min) - Abnormal results of Liver Function Test at screening - Receiving anti-epileptic medications to control active seizures or have had a documented seizure within three months of study enrollment - Incurred large cortically based ischemic infarction/encephalomalacia subsequent to TBI - Have documented history of previous TBI, psychiatric illness (DSM criteria) and/or organic brain syndrome such as Alzheimer's - Are using medications which may interfere with Amantadine and cannot be safely titrated or discontinued - Are pregnant - Have implanted cardiac pacemaker or defibrillator, cochlear implant, nerve stimulator, intracranial metal clips - Have MRI and/or TMS contraindications such as: History of claustrophobia, metal in eyes/face, shrapnel/bullet remnants in brain - Are fully conscious as indicated by a score of 6 on the Motor Function scale and/or a score of 2 on the Communication scale of the CRS-R, - Are within first year of injury - Are <18 years of age and > 65 years of age - Have an injury or condition due to blunt trauma only or non-traumatic encephalopathy - Have programmable CSF shunt or are ventilator dependent

Additional Information

Official title Amantadine + rTMS as a Neurotherapeutic for Disordered Consciousness
Principal investigator Theresa Pape, DrPH
Description The R21 research objective is to examine the safety and efficacy of repetitive transcranial magnetic stimulation (rTMS) combined with Amantadine (TMS + Amantadine) relative to rTMS Alone and Amantadine Alone for persons in chronic states of seriously impaired consciousness. The hypothesis is that provision of rTMS+Amantadine will provide a safe yet synergistic effect that induces or accelerates functional recovery. This hypothesis is based on (a) preliminary data indicating partially improved neurobehavioral functioning mechanistically related to rTMS-induced neural activity and connectivity as well as improved integrity of white fiber tracts, (b) relationship between dopamine (DA) and common traumatic brain injury (TBI) impairments, (c) role of DA in mediating consciousness, (d) the commonality between and DA and rTMS-targeted pathways, (e) clinical efficacy and safety of Amantadine, (f) mechanisms of action of Amantadine, and (g) the association between rTMS and Amantadine with up-regulating brain derived neurotrophic factor. The rationale is that pairing rTMS with Amantadine will have a complementary and synergistic effect on factors promoting conscious behavior. The specific aims are to: (1) Demonstrate that rTMS+Amantadine is safely tolerated, (2) Determine neurobehavioral effect of rTMS+Amantadine, and (3) Characterize pre-and post-treatment neural changes in neural activation. Aim 1 is based on our preliminary safety data and safety data regarding Amantadine. To address Aims 2 & 3 we use a repeated measures baseline control design with randomized treatment orders yielding three treatment groups; rTMS + Amantadine, rTMS Alone and Amantadine Alone. Analyses for Aims 2 and 3 involve comparing these treatment groups according to neurobehavioral growth trajectories, mean amount of neural activation and connectivity within and between brain regions, and indices of fiber tract directionality.
Trial information was received from ClinicalTrials.gov and was last updated in April 2016.
Information provided to ClinicalTrials.gov by Edward Hines Jr. VA Hospital.