NCT00970944

Effectiveness of Amantadine Hydrochloride for Treatment of Severe Traumatic Brain Injury (TBI)

A Multicenter Prospective Randomized Controlled Trial of the Effectiveness of Amantadine Hydrochloride in Promoting Recovery of Function Following Severe Traumatic Brain Injury

• Status: Completed
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 184 (actual)
• Sponsor: JFK Medical Center · Academic / Other
• Sex: All
• Age: 16 Years – 65 Years
• Healthy volunteers: Not accepted

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

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.

Conditions

• Traumatic Brain Injury

Interventions

Type	Name	Description
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.
DRUG	Placebo	Placebo administered twice daily.

Timeline

• Start date: 2003-02-01
• Primary completion: 2010-03-01
• Completion: 2010-03-01
• First posted: 2009-09-03
• Last updated: 2012-09-24
• Results posted: 2012-09-24

Locations

11 sites across 3 countries: United States, Denmark, Germany