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

Traumatic Brain Injury Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00627250
• Other study ID #: 12-02-06A
• Secondary ID: H133A020522
• Status: Completed
• Phase: N/A
• Start date: March 2003
• Est. completion date: November 2007

Study information

• Verified date: February 2008
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 76
• Est. completion date: November 2007
• Est. primary completion date: November 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Aggression
• Brain Injuries
• Brain Injuries, Traumatic
• Irritable Mood
• Traumatic Brain Injury

Intervention

Drug:
• Amantadine
Amantadine 100 mg every morning and 12 noon

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences	U.S. Department of Education

References & Publications (17)

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

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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Riederer P, Lange KW, Kornhuber J, Danielczyk W. Pharmacotoxic psychosis after memantine in Parkinson's disease. Lancet. 1991 Oct 19;338(8773):1022-3. — View Citation

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

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. — View Citation

Schwab RS, England AC Jr, Poskanzer DC, Young RR. Amantadine in the treatment of Parkinson's disease. JAMA. 1969 May 19;208(7):1168-70. — View Citation

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. — View Citation

Stone TW. Evidence for a non-dopaminergic action of amantadine. Neurosci Lett. 1977 May;4(6):343-6. — View Citation

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. — View Citation

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

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neuropsychiatric Inventory (Irritability Domain frequency and severity)		28 days
Secondary	Neuropsychiatric Inventory Irritability and Aggression(Caregiver distress scores)		28 days
Secondary	Neuropsychiatric Inventory Aggression Domain (frequency and severity)		28 days
Secondary	Global Impression of Change rated by clinician, individual with brain injury and caregiver		28 days

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