Utility of Amantadine Hydrochloride in the Treatment of Post-traumatic Irritability
Information source: Carolinas Healthcare System
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Irritable Mood; Aggression; Traumatic Brain Injury
Intervention: Amantadine (Drug)
Sponsored by: Carolinas Healthcare System
Official(s) and/or principal investigator(s):
Flora M Hammond, M.D., Principal Investigator, Affiliation: Carolinas Rehabilitation
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.
Official title: Utility of Amantadine Hydrochloride in the Treatment of Post-traumatic Irritability: A Randomized, Double-Blind, Placebo-Controlled Trial
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Neuropsychiatric Inventory (Irritability Domain frequency and severity)
Neuropsychiatric Inventory Irritability and Aggression(Caregiver distress scores)
Neuropsychiatric Inventory Aggression Domain (frequency and severity)
Global Impression of Change rated by clinician, individual with brain injury and caregiver
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
Minimum age: 16 Years.
Maximum age: 65 Years.
- 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
- 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.
- 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
- Clinical signs of active infection
Locations and Contacts
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Starting date: March 2003
Last updated: March 23, 2010