Amantadine for Treatment of Symptoms of the Post-traumatic Confusional State
Condition: Traumatic Brain Injury; Posttraumatic Confusional State; Delirium
MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Delirium; Confusion
Study type: Interventional
Phase: Phase 4

Summary: 
      Patients with traumatic brain injury often experience a period of acute confusion that may
      include agitation as they recover from their injuries. While this confusion generally
      resolves with time, patients may pose increased risk of injury to themselves or others during
      this period. Their behavior may also increase stress for family members and interfere with
      their ability to benefit from rehabilitation therapies. A number of different medications
      have been used to treat confusion to decrease agitation, decrease risk of injury, and improve
      participation in rehabilitation therapies. To this point, there has not been a research or
      scientific basis for knowing which medication is the best for a specific patient. The overall
      goal of this study is to conduct a scientific investigation to help determine which
      medication works best to treat confusion.

      Study hypothesis: Amantadine will reduce the severity and number of symptoms of acute
      confusion after traumatic brain injury.
    

Detailed description: 
      Patients with TBI who require inpatient rehabilitation are frequently confused at the time of
      admission for rehabilitation. Our investigations of confusion conducted as part of the TBIMSM
      have clarified the nature of confusion in early recovery after TBI. Early confusion (PTCS)
      has been found to be a complex syndrome characterized by disorientation, cognitive
      impairment, restlessness, decreased level of daytime arousal, sleep disturbance, fluctuation
      of symptoms, and psychotic-type symptoms. PTCS complicates early management of patients with
      TBI, and may contribute to increased risk of injury to patients and hospital staff, increased
      stress among family members and staff, decreased participation in therapies, increased cost
      of care, and an increased likelihood of being discharged to psychiatric or long-term care
      settings. These facts indicate the need for effective management of PTCS. Consensus regarding
      optimal treatment of the cognitive and behavioral symptoms encountered among patients with
      PTCS does not exist currently. While many agents have been tried to address such symptoms in
      TBI, few have been investigated systematically. These circumstances indicate the need for
      appropriate clinical trials to provide guidance to clinicians for medical treatment of PTCS.
      In response, the NIDRR-Traumatic Brain Injury Model System of Mississippi proposed a
      randomized, double-blinded, placebo-controlled, parallel group trial for the pharmacological
      treatment of PTCS. The agent selected for this clinical trial is amantadine, an NMDA and
      indirect dopamine agonist. This agent will be compared to placebo on response measures of
      efficacy and safety.

      Study hypothesis: Amantadine will reduce the severity and number of symptoms of PTCS.
    

Intervention name(s): Amantadine hydrochloride; Placebo capsule
Intervention type(s): Drug; Drug
Intervention description(s): 100mg administered orally twice daily x 14 days; capsule, identical to amantadine hydrochloride capsule, administered twice daily x 14 days
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; Posttraumatic Confusional State; Delirium; Amantadine; Clinical trial