Amantadine for Treatment of Symptoms of the Post-Traumatic Confusional State - Full Text View

Sponsors and Collaborators:	Methodist Rehabilitation Center Department of Education
Information provided by:	Methodist Rehabilitation Center
ClinicalTrials.gov Identifier:	NCT00693121

Purpose

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	Intervention	Phase
Traumatic Brain Injury Posttraumatic Confusional State Delirium	Drug: Amantadine hydrochloride Drug: Placebo capsule	Phase IV

MedlinePlus related topics: Rehabilitation Traumatic Brain Injury

Drug Information available for: Amantadine Amantadine hydrochloride Amantadine sulfate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
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

Further study details as provided by Methodist Rehabilitation Center:

Primary Outcome Measures:

Confusion Assessment Protocol (number of symptoms) [ Time Frame: 14 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

number of participants withdrawn from study due to fulfillment of "escape criteria" [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
Time to reach "non-confused" Confusion Assessment Protocol score [ Time Frame: <14 days ] [ Designated as safety issue: No ]

Enrollment:	79
Study Start Date:	April 2003
Estimated Study Completion Date:	June 2008
Primary Completion Date:	November 2007 (Final data collection date for primary outcome measure)

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

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.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00693121

Locations

United States, Mississippi
Methodist Rehabilitation Center
Jackson, Mississippi, United States, 39216

Sponsors and Collaborators

Methodist Rehabilitation Center

Department of Education

Investigators

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

More Information

Publications:

Sherer M, Yablon SA, Nakase-Richardson R, Nick TG. Effect of severity of post-traumatic confusion and its constituent symptoms on outcome after traumatic brain injury. Arch Phys Med Rehabil. 2008 Jan;89(1):42-7.

Nakase-Richardson R, Yablon SA, Sherer M. Prospective comparison of acute confusion severity with duration of post-traumatic amnesia in predicting employment outcome after traumatic brain injury. J Neurol Neurosurg Psychiatry. 2007 Aug;78(8):872-6. Epub 2006 Dec 18.

Sherer M, Nakase-Thompson R, Yablon SA, Gontkovsky ST. Multidimensional assessment of acute confusion after traumatic brain injury. Arch Phys Med Rehabil. 2005 May;86(5):896-904.

Nakase-Thompson R, Sherer M, Yablon SA, Nick TG, Trzepacz PT. Acute confusion following traumatic brain injury. Brain Inj. 2004 Feb;18(2):131-42.

Responsible Party:	National Institute for Disability and Rehabilitation Research ( Theresa San Augustin )
Study ID Numbers:	MethodistRC Project 1, NIDRR grant #: H133A020514
Study First Received:	June 4, 2008
Last Updated:	June 5, 2008
ClinicalTrials.gov Identifier:	NCT00693121
Health Authority:	United States: Institutional Review Board

Keywords provided by Methodist Rehabilitation Center:

Traumatic Brain Injury
Posttraumatic Confusional State
Delirium
Amantadine
Clinical trial

Study placed in the following topic categories:

Craniocerebral Trauma
Wounds and Injuries
Disorders of Environmental Origin
Central Nervous System Diseases
Confusion
Trauma, Nervous System
Brain Diseases
Cognition Disorders
Signs and Symptoms

Dopamine
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Neurologic Manifestations
Amantadine
Brain Injuries
Dementia
Neurobehavioral Manifestations
Delirium

Additional relevant MeSH terms:

Anti-Infective Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anti-Dyskinesia Agents
Nervous System Diseases
Physiological Effects of Drugs
Antiparkinson Agents
Antiviral Agents

Pharmacologic Actions
Sensory System Agents
Analgesics, Non-Narcotic
Therapeutic Uses
Dopamine Agents
Peripheral Nervous System Agents
Analgesics
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009