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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00627250
Recruitment Status : Completed
First Posted : February 29, 2008
Last Update Posted : March 24, 2010
U.S. Department of Education
Information provided by:
Atrium Health

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Irritable Mood Aggression Traumatic Brain Injury Drug: Amantadine Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 76 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Utility of Amantadine Hydrochloride in the Treatment of Post-traumatic Irritability: A Randomized, Double-Blind, Placebo-Controlled Trial
Study Start Date : March 2003
Actual Primary Completion Date : November 2007
Actual Study Completion Date : November 2007

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: A
Amantadine 100 mg every morning and 12 noon
Drug: Amantadine
Amantadine 100 mg every morning and 12 noon
Other Name: Symmetrel

Placebo Comparator: B
Placebo tablet every morning and 12 noon
Drug: Amantadine
Amantadine 100 mg every morning and 12 noon
Other Name: Symmetrel

Primary Outcome Measures :
  1. Neuropsychiatric Inventory (Irritability Domain frequency and severity) [ Time Frame: 28 days ]

Secondary Outcome Measures :
  1. Neuropsychiatric Inventory Irritability and Aggression(Caregiver distress scores) [ Time Frame: 28 days ]
  2. Neuropsychiatric Inventory Aggression Domain (frequency and severity) [ Time Frame: 28 days ]
  3. Global Impression of Change rated by clinician, individual with brain injury and caregiver [ Time Frame: 28 days ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   16 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00627250

Sponsors and Collaborators
Atrium Health
U.S. Department of Education
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Principal Investigator: Flora M Hammond, M.D. Carolinas Rehabilitation
Additional Information:
Herrman EC, Grabliks J, Engle C, et al. Antiviral activity of L-adamantanamine (amantadine). Proc Soc Exp Biol Med 1960;103:625

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Responsible Party: Flora Hammond, M.D., Carolinas HealthCare System Identifier: NCT00627250    
Other Study ID Numbers: 12-02-06A
First Posted: February 29, 2008    Key Record Dates
Last Update Posted: March 24, 2010
Last Verified: February 2008
Keywords provided by Atrium Health:
Brain Injury
Irritability and Aggression Due to Traumatic Brain Injury
Additional relevant MeSH terms:
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Brain Injuries
Brain Injuries, Traumatic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Behavioral Symptoms
Antiparkinson Agents
Anti-Dyskinesia Agents
Antiviral Agents
Anti-Infective Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents