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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00693121
Recruitment Status : Completed
First Posted : June 6, 2008
Last Update Posted : August 13, 2019
U.S. Department of Education
Information provided by:
Methodist Rehabilitation Center

Brief 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.

Condition or disease Intervention/treatment Phase
Traumatic Brain Injury Posttraumatic Confusional State Delirium Drug: Amantadine hydrochloride Drug: Placebo capsule Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 79 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Amantadine Hydrochloride for Treatment of Symptoms of the Post-traumatic Confusional State Among Neurorehabilitation Admissions With TBI: A Randomized, Double-Blind, Placebo-Controlled Trial
Study Start Date : April 2003
Actual Primary Completion Date : November 2007
Actual Study Completion Date : March 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Rehabilitation

Arm Intervention/treatment
Placebo Comparator: Placebo
Identical capsule to amantadine hydrochloride active intervention, administered twice daily x 14 days
Drug: Placebo capsule
capsule, identical to amantadine hydrochloride capsule, administered twice daily x 14 days

Active Comparator: Amantadine
Amantadine hydrochloride 100mg capsule administered twice daily x 14 days
Drug: Amantadine hydrochloride
100mg administered orally twice daily x 14 days

Primary Outcome Measures :
  1. Confusion Assessment Protocol (number of symptoms) [ Time Frame: 14 days ]

Secondary Outcome Measures :
  1. number of participants withdrawn from study due to fulfillment of "escape criteria" [ Time Frame: 14 days ]
  2. Time to reach "non-confused" Confusion Assessment Protocol score [ Time Frame: <14 days ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00693121

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United States, Mississippi
Methodist Rehabilitation Center
Jackson, Mississippi, United States, 39216
Sponsors and Collaborators
Methodist Rehabilitation Center
U.S. Department of Education
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Principal Investigator: Stuart A Yablon, M.D. Brain Injury Program, Methodist Rehabilitation Center
Study Director: Mark Sherer, Ph.D. Department of Research, Memorial Hermann/TIRR, Houston, TX
Study Director: Risa N Richardson, Ph.D. Polytrauma Program, James A. Haley Veterans Hospital, Tampa, FL
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Responsible Party: Theresa San Augustin, National Institute for Disability and Rehabilitation Research Identifier: NCT00693121    
Other Study ID Numbers: MethodistRC Project 1
NIDRR grant #: H133A020514
First Posted: June 6, 2008    Key Record Dates
Last Update Posted: August 13, 2019
Last Verified: June 2008
Keywords provided by Methodist Rehabilitation Center:
Traumatic Brain Injury
Posttraumatic Confusional State
Clinical trial
Additional relevant MeSH terms:
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Brain Injuries
Brain Injuries, Traumatic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Neurobehavioral Manifestations
Neurologic Manifestations
Neurocognitive Disorders
Mental Disorders
Antiparkinson Agents
Anti-Dyskinesia Agents
Antiviral Agents
Anti-Infective Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents