Utility of Amantadine Hydrochloride in the Treatment of Post-traumatic Irritability - Full Text View

Sponsor:	Carolinas Healthcare System
Collaborator:	U.S. Department of Education
Information provided by:	Carolinas Healthcare System
ClinicalTrials.gov Identifier:	NCT00627250

Purpose

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	Intervention
Irritable Mood Aggression Traumatic Brain Injury	Drug: Amantadine

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:

MedlinePlus related topics: Caregivers Traumatic Brain Injury

Drug Information available for: Amantadine sulfate Amantadine hydrochloride Amantadine

U.S. FDA Resources

Further study details as provided by Carolinas Healthcare System:

Primary Outcome Measures:

Neuropsychiatric Inventory (Irritability Domain frequency and severity) [ Time Frame: 28 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Neuropsychiatric Inventory Irritability and Aggression(Caregiver distress scores) [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Neuropsychiatric Inventory Aggression Domain (frequency and severity) [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Global Impression of Change rated by clinician, individual with brain injury and caregiver [ Time Frame: 28 days ] [ Designated as safety issue: No ]

Enrollment:	76
Study Start Date:	March 2003
Study Completion Date:	November 2007
Primary Completion Date:	November 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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.

Eligibility

Ages Eligible for Study:	16 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00627250

Sponsors and Collaborators

Carolinas Healthcare System

U.S. Department of Education

Investigators

Principal Investigator:

Flora M Hammond, M.D.

Carolinas Rehabilitation

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

Publications:

Gualtieri T, Chandler M, Coons TB, Brown LT. Amantadine: a new clinical profile for traumatic brain injury. Clin Neuropharmacol. 1989 Aug;12(4):258-70. Review. No abstract available.

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Schwab RS, England AC, Postkanzer DC, et al. Amantadine in the treatment of Parkinson's disease. JAMA 1969;208:1168-1170.

Beers SR, Skold A, Dixon CE, Adelson PD. Neurobehavioral effects of amantadine after pediatric traumatic brain injury: a preliminary report. J Head Trauma Rehabil. 2005 Sep-Oct;20(5):450-63.

Gianutsos G, Chute S, Dunn JP. Pharmacological changes in dopaminergic systems induced by long-term administration of amantadine. Eur J Pharmacol. 1985 Apr 16;110(3):357-61.

Aoki FY, Sitar DS. Clinical pharmacokinetics of amantadine hydrochloride. Clin Pharmacokinet. 1988 Jan;14(1):35-51. Review.

Allen RM. Role of amantadine in the management of neuroleptic-induced extrapyramidal syndromes: overview and pharmacology. Clin Neuropharmacol. 1983;6 Suppl 1:S64-73. Review. No abstract available.

Stone TW. Evidence for a non-dopaminergic action of amantadine. Neuroscience Letters 1977;4:343-346.

Weller M, Kornhuber J. A rationale for NMDA receptor antagonist therapy of the neuroleptic malignant syndrome. Med Hypotheses. 1992 Aug;38(4):329-33. Review.

Riederer P, Lange KW, Kornhuber J, Danielczyk W. Pharmacotoxic psychosis after memantine in Parkinson's disease. Lancet. 1991 Oct 19;338(8773):1022-3. No abstract available.

Edby K, Larsson J, Eek M, von Wendt L, Ostergård B. Amantadine treatment of a patient with anoxic brain injury. Childs Nerv Syst. 1995 Oct;11(10):607-9.

Chandler MC, Barnhill JL, Gualtieri CT. Amantadine for the agitated head-injury patient. Brain Inj. 1988 Oct-Dec;2(4):309-11.

Rosati DL. Early polyneuropharmacologic intervention in brain injury agitation. Am J Phys Med Rehabil. 2002 Feb;81(2):90-3.

Shiller AD, Burke DT, Kim HJ, Calvanio R, Dechman KG, Santini C. Treatment with amantadine potentiated motor learning in a patient with traumatic brain injury of 15 years' duration. Brain Inj. 1999 Sep;13(9):715-21.

Schneider WN, Drew-Cates J, Wong TM, Dombovy ML. Cognitive and behavioural efficacy of amantadine in acute traumatic brain injury: an initial double-blind placebo-controlled study. Brain Inj. 1999 Nov;13(11):863-72.

Van Reekum R, Bayley M, Garner S, Burke IM, Fawcett S, Hart A, Thompson W. N of 1 study: amantadine for the amotivational syndrome in a patient with traumatic brain injury. Brain Inj. 1995 Jan;9(1):49-53.

Zafonte RD, Watanabe T, Mann NR. Amantadine: a potential treatment for the minimally conscious state. Brain Inj. 1998 Jul;12(7):617-21.

Responsible Party:	Flora Hammond, M.D., Carolinas HealthCare System
ClinicalTrials.gov Identifier:	NCT00627250 History of Changes
Other Study ID Numbers:	12-02-06A, H133A020522
Study First Received:	February 21, 2008
Last Updated:	March 23, 2010
Health Authority:	United States: Institutional Review Board

Keywords provided by Carolinas Healthcare System:

Irritability
Aggression
Brain Injury
Amantadine
Irritability and Aggression Due to Traumatic Brain Injury

Additional relevant MeSH terms:

Aggression
Brain Injuries
Behavioral Symptoms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Amantadine
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents

Therapeutic Uses
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on February 09, 2012