Effectiveness of Amantadine Hydrochloride for Treatment of Severe Traumatic Brain Injury (TBI)
|ClinicalTrials.gov Identifier: NCT00970944|
Recruitment Status : Completed
First Posted : September 3, 2009
Results First Posted : September 24, 2012
Last Update Posted : September 24, 2012
This is a controlled trial of amantadine to improve level of function following severe traumatic brain injury.
The purpose of this study is:
- To determine whether amantadine hydrochloride, given in a dose of 200-400 mg, improves functional recovery from the vegetative and minimally conscious states
- To determine whether amantadine-related gains in function persist following drug discontinuation
- To determine the safety profile of amantadine in patients with disorders of consciousness
|Condition or disease||Intervention/treatment||Phase|
|Traumatic Brain Injury||Drug: Amantadine Hydrochloride Drug: Placebo||Phase 2 Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||184 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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 Start Date :||February 2003|
|Actual Primary Completion Date :||March 2010|
|Actual Study Completion Date :||March 2010|
Experimental: Amantadine HCL
100mg BID administered for 2 weeks, then increased to 150mg BID in week 3 if change on primary outcome measure (ie Disability Rating Scale, DRS) was less than 2 points after week 2. If change in DRS score remained less than 2 points after week 3, dose was increased to 200mg BID in week 4.
Drug: 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) 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.
Other Name: Symmetrel
|Placebo Comparator: Placebo||
Placebo administered twice daily.
- Disability Rating Scale: Functional Status [ Time Frame: Randomization and weekly for 6 weeks. The primary study endpoint was week 4 and drug washout was week 6. ]Measure of function after traumatic brain injury (TBI) intended to measure function from "coma to community." Minimum score= 0; Maximum score= 29 (High scores are indicative of greater degree of disability).
- JFK Coma Recovery Scale-Revised: Neurobehavioral Status [ Time Frame: Week 4 (primary endpoint); Week 6 (post-washout) ]
Measure of neurobehavioral function and clinical change for individuals with severe alterations of consciousness.
Minimum score= 0; Maximum score= 23 (Higher scores are indicative of a higher-level of neurobehavioral function).
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00970944
|United States, Massachusetts|
|Braintree Rehabilitation Hospital|
|Braintree, Massachusetts, United States, 02184|
|United States, Mississippi|
|Methodist Rehabilitation Center|
|Jackson, Mississippi, United States, 39216|
|United States, New York|
|New York, New York, United States, 10032|
|Sunnyview Rehabilitation Hospital|
|Schenectady, New York, United States, 12308|
|United States, North Carolina|
|Charlotte Rehabilitation Center|
|Charlotte, North Carolina, United States, 28203|
|United States, Pennsylvania|
|Moss Rehabilitation Research Institute|
|Elkins Park, Pennsylvania, United States, 19027|
|Bryn Mawr Rehabilitation Hospital|
|Malvern, Pennsylvania, United States, 19355|
|United States, Texas|
|Texas NeuroRehabilitation Center|
|Austin, Texas, United States, 78745|
|Hvidovre University Hospital|
|Hvidovre, Denmark, DK 2650|
|Neurologische Klinik Bad Aibling|
|Bad Aibling, Germany, 83043|
|Neresheim, Germany, 73450|
|Principal Investigator:||Joseph T. Giacino, Ph.D.||Spaulding Rehabilitation Hospital|
|Principal Investigator:||John Whyte, MD, Ph.D.||Moss Rehabilitation Research Institute|