Utility of Amantadine Hydrochloride in the Treatment of Post-traumatic Irritability

April 19, 2022 updated by: Wake Forest University Health Sciences

Utility of Amantadine Hydrochloride in the Treatment of Post-traumatic Irritability: A Randomized, Double-Blind, Placebo-Controlled Trial

The purpose of this study is to determine if amantadine hydrochloride given 100 mg in the morning and at noon is safe and effective in the treatment of mood and behavior changes (i.e. irritability) after sustaining traumatic brain injury.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Amantadine hydrochloride is a drug used commonly in clinical practice at the Carolinas Rehabilitation for the treatment of mood and behavior changes following traumatic brain injury. Clinical observation suggests that the use of amantadine improves caregiver report of "irritability" though there are no studies to validate this observation. This study investigates the efficacy and side effect profile of amantadine hydrochloride given in 2 doses of 100 mgs each. Subjects are screened during regularly scheduled clinic appointments for the presence of irritability. If they are interested in possible participation in the study, they will be invited to meet with the research coordinator who will obtain informed consent. If the subject meets all the inclusion/exclusion requirements, they will leave clinic with study medication and begin taking the drug the next day. There will be a safety call between day 3 and 5 where the dose may be reduced to once per day. Follow-up assessment occurs at day 14 (by phone) and day 28 (in clinic). At study completion, the subject will have the opportunity to receive a prescription for amantadine as part of ongoing clinical care.

Study Type

Interventional

Enrollment (Actual)

76

Phase

  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 65 years (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Closed head injury (defined as brain injury or impaired brain function resulting from externally inflicted trauma without penetrating injury) at least 6 months prior to enrollment.
  • Age at time of enrollment: 16 - 65 inclusive (i.e., on or after 16th birthday, up to day before 66th birthday).
  • Voluntary informed consent of patient and informant.
  • Subject and informant willing to comply with the protocol, & are available for all scheduled clinic visits.
  • Neuropsychiatric Inventory (NPI) Irritability Domain score > 2.
  • Medically and neurologically stable during the month prior to enrollment.
  • If taking antidepressant, anxiolytic, hypnotic, or stimulant medications, no change anticipated in these medications during the month prior to enrollment.
  • No change in therapies or medications planned during the 28-day participation.
  • No surgeries planned during the 28-day participation.
  • Vision, hearing, speech, motor function, and comprehension must be sufficient for compliance with all testing procedures. Ability to interact and verbalize sufficient to participate in assessments.
  • Informant (family member or close friend) who lives with the participant with daily interaction in order to observe occurrences of irritability.

Exclusion Criteria:

  • Patients without a reliable informant
  • Penetrating head injury
  • Injury < 6 months prior to enrollment
  • Inability to interact sufficient for communication with caregiver
  • Acute and rehabilitation records unavailable or incomplete
  • DSM-IV diagnosis of schizophrenia or psychosis
  • Diagnosis of progressive or additional neurologic disease (such as, Alzheimer's disease, parkinson's disease, multi-infarct dementia, other cerebrovascular disorders with dementia, prior cerebrovascular accident, Huntington's disease, olivopontocerebellar atrophy, multisystem atrophy, multiple sclerosis, ALS, CNS tumor, progressive supranuclear palsy).
  • Diagnosis of seizure in the month prior to enrollment.
  • Previous allergy or adverse reaction to study drug
  • Ingestion of amantadine hydrochloride during the month prior to enrollment.
  • Concomitant use of neuroleptic agents or phenelzine
  • Creatinine clearance <60
  • Pregnancy (Beta-HCG performed on all females of child-bearing potential) and lactating females.
  • Clinical signs of active infection

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: A
Amantadine 100 mg every morning and 12 noon
Drug: Amantadine
Amantadine 100 mg every morning and 12 noon
Other Names:
  • Symmetrel
PLACEBO_COMPARATOR: B
Placebo tablet every morning and 12 noon
Drug: Amantadine
Amantadine 100 mg every morning and 12 noon
Other Names:
  • Symmetrel

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Neuropsychiatric Inventory (Irritability Domain frequency and severity)
Time Frame: 28 days
28 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Neuropsychiatric Inventory Irritability and Aggression(Caregiver distress scores)
Time Frame: 28 days
28 days
Neuropsychiatric Inventory Aggression Domain (frequency and severity)
Time Frame: 28 days
28 days
Global Impression of Change rated by clinician, individual with brain injury and caregiver
Time Frame: 28 days
28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Wake Forest University Health Sciences

Collaborators

U.S. Department of Education

Investigators

  • Principal Investigator: Flora M Hammond, M.D., Carolinas Rehabilitation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2003

Primary Completion (ACTUAL)

November 1, 2007

Study Completion (ACTUAL)

November 1, 2007

Study Registration Dates

First Submitted

February 21, 2008

First Submitted That Met QC Criteria

February 28, 2008

First Posted (ESTIMATE)

February 29, 2008

Study Record Updates

Last Update Posted (ACTUAL)

April 25, 2022

Last Update Submitted That Met QC Criteria

April 19, 2022

Last Verified

February 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 12-02-06A
  • H133A020522

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Aggression

Clinical Trials on Amantadine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Paraguay

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe