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

Traumatic Brain Injury Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00693121
• Other study ID #: MethodistRC Project 1
• Secondary ID: NIDRR grant #: H
• Status: Completed
• Phase: Phase 4
• Start date: April 2003
• Est. completion date: March 2019

Study information

• Verified date: June 2008
• Source: Methodist Rehabilitation Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 79
• Est. completion date: March 2019
• Est. primary completion date: November 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• Confusion
• Delirium
• Posttraumatic Confusional State
• Traumatic Brain Injury

Intervention

Drug:
• Amantadine hydrochloride
100mg administered orally twice daily x 14 days
• Placebo capsule
capsule, identical to amantadine hydrochloride capsule, administered twice daily x 14 days

Locations

Country	Name	City	State
United States	Methodist Rehabilitation Center	Jackson	Mississippi

Sponsors (2)

Lead Sponsor	Collaborator
Methodist Rehabilitation Center	U.S. Department of Education

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. doi: 10.1136/jnnp.2006.104190. Epub 2006 Dec 18. — View Citation

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. doi: 10.1080/0269905031000149542. — View Citation

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. doi: 10.1016/j.apmr.2004.09.029. — View Citation

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. doi: 10.1016/j.apmr.2007.08.128. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Confusion Assessment Protocol (number of symptoms)		14 days
Secondary	number of participants withdrawn from study due to fulfillment of "escape criteria"		14 days
Secondary	Time to reach "non-confused" Confusion Assessment Protocol score		<14 days