Clinical Trial: Amantadine for the Treatment of Traumatic Brain Injury Irritability and Aggression: A Multi-site Study

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Multi-Center, Parallel-Group, Randomized, Double-Blind, Placebo-Controlled Trial of Amantadine Hydrochloride in the Treatment of Chronic Traumatic Brain Injury Irritability and

Brief Summary: The purpose of this study is to study the effect of amantadine on irritability and aggression caused by traumatic brain injury.

Detailed Summary:

PURPOSE OF PROJECT: To study the effect of amantadine 100 mg administered twice daily compared to placebo on irritability from baseline to treatment Day 28.

SUMMARY OF PROJECT: It is anticipated that 168 subjects with 168 corresponding subject informants will be recruited for the study. Carolinas Rehabilitation, the lead center, and 5 collaborating centers will enroll approximately 28 subjects each.

Subjects will be recruited primarily from the clinics. Also, letters will be sent to patients in our data base. If the first encounter with research personnel is by telephone, the research assistant will obtain verbal (telephone) consent from the subject's informant for the Neuropsychiatric Inventory (NPI) for subject irritability. The score on this questionnaire must be ≥ 6 for qualification. This allows pre-screening to take place and avoid an unnecessary clinic visit.

Subjects who consent and qualify will be randomized in a 1:1 ratio, amantadine to placebo. Stratification to randomization group will occur based on the presence of depression defined by a Beck's Depression Inventory-II (BDI-II) score ≥ 13. Randomized subjects will receive amantadine or placebo 100 mg twice daily every morning and 12 Noon. There will be 4 clinic visits. Visits will occur at baseline, for consenting and screening, day 28, day 60 and day 90. At all 4 clinic visits, both the subject and the informant will be given questionnaires regarding the subject's behavior and mood. Follow up phone calls will occur each week that the subject is not seen in the clinic until the end of the study. Follow up phone calls will assess for study medication compliance, adverse events and concomitant medication changes. Day 60 ends the period of the Randomized Clinical Trial phase of the study and the subjec
Sponsor: Carolinas Healthcare System

Current Primary Outcome: Neuropsychiatric Inventory Irritability Domain [ Time Frame: 28 days ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Neuropsychiatric Inventory Aggression Domain [ Time Frame: 28 days and 60 days ]
  • State Anger Aggression Expression Inventory -- II [ Time Frame: 28 and 60 days ]
  • Neuropsychiatric Inventory Irritability Domain [ Time Frame: 60 days ]
  • Neuropsychiatric Inventory Caregiver Distress Score for Irritability and Aggression Domains [ Time Frame: 28 and 60 days ]
  • Clinical Global Impressions [ Time Frame: 28 and 60 days ]
  • Global Impression of Change [ Time Frame: 28 and 60 days ]
  • Short Form-12 [ Time Frame: 28 and 60 days ]
  • Satisfaction With Life Scale [ Time Frame: 28 and 60 days ]
  • Patient Health Questionnaire - 9 [ Time Frame: 28 and 60 days ]
  • Beck Depression Inventory II [ Time Frame: 28 and 60 days ]
  • Neuropsychologic tests [ Time Frame: 28 and 60 days ]
    Digit Span, Trail Making Test, Controlled Oral Word Association Test, California Verbal Learning Test, Processing Speed Index


Original Secondary Outcome:

  • Neuropsychiatric Inventory Aggression Domain [ Time Frame: 28 days and 60 days ]
  • State Anger Aggression Expression Inventory -- II [ Time Frame: 28 and 60 days ]
  • Neuropsychiatric Inventory Irritability Domain [ Time Frame: 60 days ]
  • Neuropsychiatric Inventory Caregiver Distress Score for Irritability and Aggression Domains [ Time Frame: 28 and 60 days ]
  • Clinical Global Impressions [ Time Frame: 28 and 60 days ]
  • Global Impression of Change [ Time Frame: 28 and 60 days ]
  • Short Form-12 [ Time Frame: 28 and 60 days ]
  • Glasgow Coma Scale - Extended [ Time Frame: 28 and 60 days ]
  • Satisfaction With Life Scale [ Time Frame: 28 and 60 days ]
  • Patient Health Questionnaire - 9 [ Time Frame: 28 and 60 days ]
  • Beck Depression Inventory II [ Time Frame: 28 and 60 days ]
  • Fatigue Impact Scale [ Time Frame: 28 and 60 days ]
  • Family Assessment Device General Functioning Scale [ Time Frame: 28 and 60 days ]
  • Neuropsychologic tests [ Time Frame: 28 and 60 days ]


Information By: Carolinas Healthcare System

Dates:
Date Received: October 23, 2008
Date Started: August 2009
Date Completion:
Last Updated: August 11, 2014
Last Verified: August 2014