Amantadine + rTMS as a Neurotherapeutic for Disordered Consciousness

NCT02025439 | Completed Results DMC

• 1 other identifier: 1R21HD075192
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Traumatic Brain Injury

Keywords

Traumatic Brain Injury; Transcranial Magnetic Stimulation; Amantadine; Vegetative State; Minimally Conscious State

Outcome Measures

Primary Outcomes (1)

• Intensity of Adverse Event

  If an adverse event occurred, the intensity was also indicated. The intensity of an adverse event was determined using a scale from 1-5 with 5 being the worst. The purpose of the study is to examine safety of rTMS combined with AMA relative to rTMS Alone and AMA alone. Results are not reported "per arm" rather, the arms are combined so as to compare the outcome when the interventions are provided separately (i.e., rTMS alone and amantadine alone) vs interventions are combined (rTMS +Amantadine alone).

  30 days after treatment "alone" and an additional 30 days after treatment "combined" (i.e., 60 days)

Study Arms (2)

rTMS Alone followed by rTMS+AMA

EXPERIMENTAL

Subjects assigned to rTMS Alone will receive 30 sessions of rTMS. Two rTMS sessions will be provided per day, four days per week.After first completing rTMS Alone, subjects 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.

Device: rTMS; Drug: Amantadine

AMA Alone followed by rTMS+AMA

EXPERIMENTAL

Subjects who are assigned to the Amantadine Alone group will receive 28 doses of Amantadine (100mg BID) every day for 28 days. After first completing Amantadine Alone subjects 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.

Device: rTMS; Drug: Amantadine

Interventions

rTMS DEVICE

Also known as: Repetitive Transcranial Magnetic Stimulation

AMA Alone followed by rTMS+AMA; rTMS Alone followed by rTMS+AMA

Amantadine DRUG

Also known as: Symadine, Symmetrel

AMA Alone followed by rTMS+AMA; rTMS Alone followed by rTMS+AMA

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Edward Hines Jr. VA Hospital: lead

Study Sites (2)

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Edward Hines, Jr. VA Hospital

Hines, Illinois, 60141, United States

Location

Related Publications (2)

• 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. doi: 10.1097/00001199-200609000-00063.

  PMID: 16983227 BACKGROUND

• 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.

  PMID: 20633400 BACKGROUND

MeSH Terms

Conditions

Brain Injuries, Traumatic; Persistent Vegetative State

Interventions

Transcranial Magnetic Stimulation; Amantadine

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Brain Damage, Chronic; Unconsciousness; Consciousness Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Theresa Bender-Pape
• Organization: Edward Hines VA Hospital

Theresa.BenderPape@va.gov

708-202-4953

Study Officials

• Theresa BenderPape, DrPH

  Edward Hines Jr. VA Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: December 23, 2013
• First Posted: January 1, 2014
• Study Start: February 1, 2014
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: August 24, 2020
• Results First Posted: August 24, 2020

Record last verified: 2020-08

Locations

US (2)