DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



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

Information source: Carolinas Healthcare System
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Irritable Mood; Aggression; Traumatic Brain Injury

Intervention: Amantadine (Drug)

Phase: N/A

Status: Completed

Sponsored by: Carolinas Healthcare System

Official(s) and/or principal investigator(s):
Flora M Hammond, M.D., Principal Investigator, Affiliation: Carolinas Rehabilitation

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.

Clinical Details

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

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: Neuropsychiatric Inventory (Irritability Domain frequency and severity)

Secondary outcome:

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

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

Minimum age: 16 Years. Maximum age: 65 Years. Gender(s): Both.

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

Locations and Contacts

Additional Information

Related 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.

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.

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, OstergÄrd 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.

Starting date: March 2003
Ending date: November 2007
Last updated: February 28, 2008

Page last updated: June 20, 2008

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2012