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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Amantadine Hydrochloride for Treatment of Symptoms of the Post-traumatic Confusional State Among Neurorehabilitation Admissions With TBI: A Randomized, Double-Blind, Placebo-Controlled Trial

Conditions
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Traumatic Brain Injury, Posttraumatic Confusional State, Delirium

Intervention / Treatment
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* Drug: Amantadine hydrochloride
* Drug: Placebo capsule


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Identical capsule to amantadine hydrochloride active intervention, administered twice daily x 14 days | Drug: Placebo capsule<br>* capsule, identical to amantadine hydrochloride capsule, administered twice daily x 14 days<br>|
| Active Comparator: Amantadine<br>Amantadine hydrochloride 100mg capsule administered twice daily x 14 days | Drug: Amantadine hydrochloride<br>* 100mg administered orally twice daily x 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confusion Assessment Protocol (number of symptoms) |  | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of participants withdrawn from study due to fulfillment of escape criteria |  | 14 days | 
| Time to reach non-confused Confusion Assessment Protocol score |  | <14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Traumatic Brain Injury, Posttraumatic Confusional State, Delirium, Amantadine, Clinical trial