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

NCT ID: NCT00627250

Last Updated: 2022-04-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

76 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-03-31

Study Completion Date

2007-11-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Irritable Mood Aggression Traumatic Brain Injury

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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A

Amantadine 100 mg every morning and 12 noon

Group Type EXPERIMENTAL

Amantadine

Intervention Type DRUG

Amantadine 100 mg every morning and 12 noon

B

Placebo tablet every morning and 12 noon

Group Type PLACEBO_COMPARATOR

Amantadine

Intervention Type DRUG

Amantadine 100 mg every morning and 12 noon

Interventions

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Amantadine

Amantadine 100 mg every morning and 12 noon

Intervention Type DRUG

Other Intervention Names

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Symmetrel

Eligibility Criteria

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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
Minimum Eligible Age

16 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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U.S. Department of Education

FED

Sponsor Role collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Flora M Hammond, M.D.

Role: PRINCIPAL_INVESTIGATOR

Carolinas Rehabilitation

References

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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. No abstract available.

Reference Type BACKGROUND
PMID: 2680078 (View on PubMed)

HERRMANN EC Jr, GABLIKS J, ENGLE C, PERLMAN PL. Agar diffusion method for detection and bioassay of antiviral antibiotics. Proc Soc Exp Biol Med. 1960 Mar;103:625-8. doi: 10.3181/00379727-103-25617. No abstract available.

Reference Type BACKGROUND
PMID: 14401357 (View on PubMed)

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. No abstract available.

Reference Type BACKGROUND
PMID: 5818715 (View on PubMed)

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. doi: 10.1097/00001199-200509000-00006.

Reference Type BACKGROUND
PMID: 16170253 (View on PubMed)

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. doi: 10.1016/0014-2999(85)90564-3.

Reference Type BACKGROUND
PMID: 2861102 (View on PubMed)

Aoki FY, Sitar DS. Clinical pharmacokinetics of amantadine hydrochloride. Clin Pharmacokinet. 1988 Jan;14(1):35-51. doi: 10.2165/00003088-198814010-00003.

Reference Type BACKGROUND
PMID: 3280212 (View on PubMed)

Allen RM. Role of amantadine in the management of neuroleptic-induced extrapyramidal syndromes: overview and pharmacology. Clin Neuropharmacol. 1983;6 Suppl 1:S64-73. doi: 10.1097/00002826-198300061-00009. No abstract available.

Reference Type BACKGROUND
PMID: 6196112 (View on PubMed)

Stone TW. Evidence for a non-dopaminergic action of amantadine. Neurosci Lett. 1977 May;4(6):343-6. doi: 10.1016/0304-3940(77)90181-1.

Reference Type BACKGROUND
PMID: 19556187 (View on PubMed)

Weller M, Kornhuber J. A rationale for NMDA receptor antagonist therapy of the neuroleptic malignant syndrome. Med Hypotheses. 1992 Aug;38(4):329-33. doi: 10.1016/0306-9877(92)90027-a.

Reference Type BACKGROUND
PMID: 1337136 (View on PubMed)

Riederer P, Lange KW, Kornhuber J, Danielczyk W. Pharmacotoxic psychosis after memantine in Parkinson's disease. Lancet. 1991 Oct 19;338(8773):1022-3. doi: 10.1016/0140-6736(91)91888-2. No abstract available.

Reference Type BACKGROUND
PMID: 1681331 (View on PubMed)

Edby K, Larsson J, Eek M, von Wendt L, Ostergard B. Amantadine treatment of a patient with anoxic brain injury. Childs Nerv Syst. 1995 Oct;11(10):607-9. doi: 10.1007/BF00301001.

Reference Type BACKGROUND
PMID: 8556729 (View on PubMed)

Chandler MC, Barnhill JL, Gualtieri CT. Amantadine for the agitated head-injury patient. Brain Inj. 1988 Oct-Dec;2(4):309-11. doi: 10.3109/02699058809150901.

Reference Type BACKGROUND
PMID: 3203176 (View on PubMed)

Rosati DL. Early polyneuropharmacologic intervention in brain injury agitation. Am J Phys Med Rehabil. 2002 Feb;81(2):90-3. doi: 10.1097/00002060-200202000-00003.

Reference Type BACKGROUND
PMID: 11807342 (View on PubMed)

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. doi: 10.1080/026990599121269.

Reference Type BACKGROUND
PMID: 10507453 (View on PubMed)

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. doi: 10.1080/026990599121061.

Reference Type BACKGROUND
PMID: 10579658 (View on PubMed)

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. doi: 10.3109/02699059509004571.

Reference Type BACKGROUND
PMID: 7874096 (View on PubMed)

Zafonte RD, Watanabe T, Mann NR. Amantadine: a potential treatment for the minimally conscious state. Brain Inj. 1998 Jul;12(7):617-21. doi: 10.1080/026990598122386.

Reference Type BACKGROUND
PMID: 9653525 (View on PubMed)

Related Links

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Other Identifiers

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H133A020522

Identifier Type: -

Identifier Source: secondary_id

12-02-06A

Identifier Type: -

Identifier Source: org_study_id

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