Amantadine for the Treatment of Traumatic Brain Injury Irritability and Aggression: A Multi-site Study
Condition: Brain Injury; Aggression
MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Wounds and Injuries; Aggression
Study type: Interventional

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

Detailed description: 
      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 subjects
      will begin the 1 month continuation phase of the study when all participants receive active
      amantadine.

      The following questionnaires will be used as measures of irritability for the subject and the
      informant: Neuropsychiatric Inventory (NPI), State Trait Anger Expression Inventory
      (STAXI-2), and Global Impression of Change.

      The following questionnaires will be dispensed to the subject only: Short Form -12,
      Satisfaction With Life Scale, Patient Health Questionnaire, Beck Depression Inventory, Brief
      Symptom Inventory, Family Assessment Device, Fatigue Impact Scale, and tests of cognitive
      function. The Glasgow Outcome Score-Extended will be completed by the research assistant
      using information obtained primarily from the informant.

      The Investigator will complete the Clinical Global Impression of change at Visits 1, 2, 3,
      and 4.

      History and Physical Exam, creatinine level (kidney function) will be obtained for safety and
      tolerability. Serum pregnancy tests will be drawn at screening for females of childbearing
      potential.
    

Intervention name(s): Amantadine Hydrochloride; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 100 mg every morning and noon; one placebo tablet every morning and 12 Noon
Other intervention name(s): Symmetrel
Intervention MeSH terms: Amantadine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: traumatic brain injury; irritability; aggression; amantadine; behavior