Amantadine for Treatment of Symptoms of the Post-traumatic Confusional State

Methodist Rehabilitation Center

Status and phase: Completed; Phase 4

Conditions: Traumatic Brain Injury; Posttraumatic Confusional State; Delirium

Treatments: Drug: Placebo capsule; Drug: Amantadine hydrochloride

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT00693121

MethodistRC Project 1

NIDRR grant #: H133A020514

Details and patient eligibility

About

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.

Full 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.

Enrollment: 79 patients

Sex: All

Ages: 16 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Acute Traumatic Brain Injury (≤90 days postinjury)
• Responsive (not fulfilling criteria for Minimally Conscious State)
• Meet PTCS criteria on 2 consecutive examinations (as determined by the Confusion Assessment Protocol)
• Initial neurorehabilitation hospital admission
• Anticipated ≥2 week length-of-stay after meeting PTCS criteria

Exclusion criteria

• Preexisting seizure disorder
• Prior history of hospitalization for psychiatric condition

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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79 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Identical capsule to amantadine hydrochloride active intervention, administered twice daily x 14 days

Treatment:

Drug: Placebo capsule

Amantadine

Active Comparator group

Description:

Amantadine hydrochloride 100mg capsule administered twice daily x 14 days

Treatment:

Drug: Amantadine hydrochloride