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

NCT ID: NCT00693121

Last Updated: 2023-10-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 79 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-04-30
• Study Completion Date: 2019-03-31

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.

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.

Conditions

Traumatic Brain Injury; Posttraumatic Confusional State; Delirium

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo capsule

Intervention Type: DRUG

capsule, identical to amantadine hydrochloride capsule, administered twice daily x 14 days

Amantadine

Amantadine hydrochloride 100mg capsule administered twice daily x 14 days

Group Type: ACTIVE_COMPARATOR

Amantadine hydrochloride

Intervention Type: DRUG

100mg administered orally twice daily x 14 days

Interventions

Amantadine hydrochloride

100mg administered orally twice daily x 14 days

Intervention Type: DRUG

Placebo capsule

capsule, identical to amantadine hydrochloride capsule, administered twice daily x 14 days

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

U.S. Department of Education

FED

Sponsor Role: collaborator

Methodist Rehabilitation Center

OTHER

Sponsor Role: lead

Responsible Party

National Institute for Disability and Rehabilitation Research

Principal Investigators

Stuart A Yablon, M.D.

Role: PRINCIPAL_INVESTIGATOR

Brain Injury Program, Methodist Rehabilitation Center

Mark Sherer, Ph.D.

Role: STUDY_DIRECTOR

Department of Research, Memorial Hermann/TIRR, Houston, TX

Risa N Richardson, Ph.D.

Role: STUDY_DIRECTOR

Polytrauma Program, James A. Haley Veterans Hospital, Tampa, FL

Locations

Methodist Rehabilitation Center

Jackson, Mississippi, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 18164329 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17178822 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15895334 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 14660226 (View on PubMed)

Other Identifiers

NIDRR grant #: H133A020514

Identifier Type: -

Identifier Source: secondary_id

MethodistRC Project 1

Identifier Type: -

Identifier Source: org_study_id