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Amantadine + rTMS as a Neurotherapeutic for Disordered Consciousness

Information source: Edward Hines Jr. VA Hospital
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Traumatic Brain Injury

Intervention: rTMS (Device); Amantadine (Drug)

Phase: N/A

Status: Recruiting

Sponsored by: Edward Hines Jr. VA Hospital

Official(s) and/or principal investigator(s):
Theresa Pape, DrPH, Principal Investigator, Affiliation: Edward Hines Jr. VA Hospital

Overall contact:
Ann Guernon, MS, CCRC, Phone: 708-202-8387, Ext: 23114, Email: Ann.Guernon@va.gov

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.

Clinical Details

Official title: Amantadine + rTMS as a Neurotherapeutic for Disordered Consciousness

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Safety

Secondary outcome:

Disorders of Consciousness Scale (DOCS) Neurobehavioral Growth Trajectories

Change from Baseline in Functional magnetic resonance imaging (fMRI)

Detailed 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.

Eligibility

Minimum age: 18 Years. Maximum age: 64 Years. Gender(s): Both.

Criteria:

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

Locations and Contacts

Ann Guernon, MS, CCRC, Phone: 708-202-8387, Ext: 23114, Email: Ann.Guernon@va.gov

Northwestern Memorial Hospital, Chicago, Illinois 60611, United States; Recruiting
Theresa Pape, DrPH, Email: Theresa.Pape@va.gov
Joshua Rosenow, MD, Sub-Investigator

Edward Hines, Jr. VA Hospital, Hines, Illinois 60141, United States; Recruiting
Theresa Pape, DrPH, Phone: 708-202-4953, Email: Theresa.Pape@va.gov
Theresa Pape, DrPH, Principal Investigator

Additional Information

Related publications:

Pape TL, Rosenow J, Lewis G. Transcranial magnetic stimulation: a possible treatment for TBI. J Head Trauma Rehabil. 2006 Sep-Oct;21(5):437-51. Review.

Louise-Bender Pape T, Rosenow J, Lewis G, Ahmed G, Walker M, Guernon A, Roth H, Patil V. Repetitive transcranial magnetic stimulation-associated neurobehavioral gains during coma recovery. Brain Stimul. 2009 Jan;2(1):22-35. doi: 10.1016/j.brs.2008.09.004. Epub 2008 Oct 23.

Starting date: February 2014
Last updated: August 3, 2015

Page last updated: August 23, 2015

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