Effectiveness of Amantadine Hydrochloride for Treatment of Severe Traumatic Brain Injury (TBI)
Information source: JFK Medical Center
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Traumatic Brain Injury
Intervention: Amantadine Hydrochloride (Drug); Placebo (Drug)
Phase: Phase 2/Phase 3
Status: Completed
Sponsored by: JFK Medical Center Official(s) and/or principal investigator(s): Joseph T. Giacino, Ph.D., Principal Investigator, Affiliation: Spaulding Rehabilitation Hospital John Whyte, MD, Ph.D., Principal Investigator, Affiliation: Moss Rehabilitation Research Institute
Summary
This is a controlled trial of amantadine to improve level of function following severe
traumatic brain injury.
The purpose of this study is:
1. To determine whether amantadine hydrochloride, given in a dose of 200-400 mg, improves
functional recovery from the vegetative and minimally conscious states
2. To determine whether amantadine-related gains in function persist following drug
discontinuation
3. To determine the safety profile of amantadine in patients with disorders of
consciousness
Clinical Details
Official title: A Multicenter Prospective Randomized Controlled Trial of the Effectiveness of Amantadine Hydrochloride in Promoting Recovery of Function Following Severe Traumatic Brain Injury
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Disability Rating Scale: Functional Status
Secondary outcome: JFK Coma Recovery Scale-Revised: Neurobehavioral Status
Detailed description:
Severe traumatic brain injury may result in severe disorders of consciousness (DOC),
including coma, the vegetative state (VS) and the minimally conscious state (MCS). The
longer the duration of impaired consciousness, the worse the ultimate functional prognosis,
with only about half of those individuals who remain unconscious for a month post-TBI
regaining consciousness within a year. The severe functional disability associated with
prolonged DOC places enormous emotional, financial, ethical, and logistical strains on
caregivers and major resource demands on society. Numerous treatments have been recommended
to hasten the return of consciousness or improve the ultimate level of recovery, including
various psychotropic drugs, "coma stimulation" therapy and others. However, none of these
treatments has proven efficacy in well-controlled research. The main obstacles to Class I
evidence in this area have been the small samples of individuals with serious DOC in
individual facilities, the variability of recovery trajectories within this heterogeneous
population, and the reluctance to undertake placebo controlled trials.
In the proposed study, 7 facilities (including two with TBI Model Systems designations) that
participated in a multi-center research network called the Consciousness Consortium, join
with four additional brain injury rehabilitation centers (two in the U. S. and two in Europe)
and a Data Coordinating Center at Columbia University, to conduct a prospective double blind
randomized controlled trial of amantadine hydrochloride. 184 patients who remain in VS or
MCS 4 - 16 weeks post-TBI will be randomized in a stratified fashion to 4 weeks of
amantadine (200 - 400 mg/day) vs. placebo, followed by a 2-week washout period. The
Disability Rating Scale (DRS) will be the primary dependent variable with the Coma Recovery
Scale-Revised (CRS-R) serving as a supplementary measure. We hypothesize superior recovery
in the amantadine group and maintenance of that advantage after washout. We will also
explore whether treatment response differs by time post-injury and by diagnosis (i. e., VS or
MCS) at treatment onset, and whether specific outcomes of importance to caregivers are
achieved more often in the amantadine group. We have developed plans for intensive education
of caregivers and clinicians about this study to address perceived barriers to enrollment
and will also use the information gathered during these interactions to develop
consumer-oriented dissemination activities. Project outputs and findings will be
disseminated to appropriate consumer and professional audiences using a variety of formats
and will include: (1) improved family member understanding of DOC which will facilitate
improved adjustment and caregiving and (2) clear guidance to clinicians regarding the
effectiveness of amantadine for persons with DOC.
Eligibility
Minimum age: 16 Years.
Maximum age: 65 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Individuals between ages 16 and 65 with traumatic brain injury as defined by the TBI
Model System syllabus (i. e., damage to brain tissue caused by an external mechanical
force as evidenced by loss of consciousness or post-traumatic amnesia due to brain
trauma, skull fracture, or objective neurological findings that can be reasonably
attributed to TBI on physical or mental status examination).
- Individuals are at least 4 weeks but less than 16 weeks post-injury and have a
Disability Rating Scale (DRS) score at enrollment of 12 or greater, and no consistent
command following or functional communication (as defined by the JFK.
Exclusion Criteria:
- Women who are pregnant,
- Individuals with missile-type penetrating brain injury,
- Premorbid major CNS/developmental abnormality (e. g., mental retardation, prior
significant brain damage, etc.),
- History of more than 1 seizure (clinical or electrographic, but not including
epileptiform or other irritative discharges) in the 4 weeks prior to enrollment
(individuals with premorbid idiopathic epilepsy are eligible to enroll under two
conditions: a) if their pre-injury seizure frequency was less than once/month and
they have had no more than 1 seizure/month since injury and b) if a clear provocation
was present that would otherwise disqualify a subject, the subject can be enrolled,
since these events would not be considered idiopathic),
- Prior exposure to AH post-TBI,
- Unwillingness to discontinue or change confounding psychotropic drugs prior to
enrollment, OR
- Allergy or medical contraindication to AH and significant impairment of renal
function (as evidenced by a calculated creatinine clearance of < 60 ml/min).
Locations and Contacts
Hvidovre University Hospital, Hvidovre DK 2650, Denmark
Neurologische Klinik Bad Aibling, Bad Aibling 83043, Germany
Fachkrankenhaus Neresheim, Neresheim 73450, Germany
Braintree Rehabilitation Hospital, Braintree, Massachusetts 02184, United States
Methodist Rehabilitation Center, Jackson, Mississippi 39216, United States
Columbia University, New York, New York 10032, United States
Sunnyview Rehabilitation Hospital, Schenectady, New York 12308, United States
Charlotte Rehabilitation Center, Charlotte, North Carolina 28203, United States
Moss Rehabilitation Research Institute, Elkins Park, Pennsylvania 19027, United States
Bryn Mawr Rehabilitation Hospital, Malvern, Pennsylvania 19355, United States
Texas NeuroRehabilitation Center, Austin, Texas 78745, United States
Additional Information
Starting date: February 2003
Last updated: September 11, 2012
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