NCT00627250

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.

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
76

participants targeted

Target at P50-P75 for not_applicable

Timeline
Completed

Started Mar 2003

Longer than P75 for not_applicable

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2003

Completed
4.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2007

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2007

Completed
4 months until next milestone

First Submitted

Initial submission to the registry

February 21, 2008

Completed
8 days until next milestone

First Posted

Study publicly available on registry

February 29, 2008

Completed
Last Updated

April 25, 2022

Status Verified

February 1, 2008

Enrollment Period

4.7 years

First QC Date

February 21, 2008

Last Update Submit

April 19, 2022

Conditions

Irritable MoodAggressionTraumatic Brain Injury

Keywords

IrritabilityAggressionBrain InjuryAmantadineIrritability and Aggression Due to Traumatic Brain Injury

Outcome Measures

Primary Outcomes (1)

  • Neuropsychiatric Inventory (Irritability Domain frequency and severity)

    28 days

Secondary Outcomes (3)

  • Neuropsychiatric Inventory Irritability and Aggression(Caregiver distress scores)

    28 days

  • Neuropsychiatric Inventory Aggression Domain (frequency and severity)

    28 days

  • Global Impression of Change rated by clinician, individual with brain injury and caregiver

    28 days

Study Arms (2)

A

EXPERIMENTAL

Amantadine 100 mg every morning and 12 noon

Drug: Amantadine

B

PLACEBO COMPARATOR

Placebo tablet every morning and 12 noon

Drug: Amantadine

Interventions

AmantadineDRUG

Amantadine 100 mg every morning and 12 noon

Also known as: Symmetrel
AB

Eligibility Criteria

Age16 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (17)

  • 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.

    PMID: 2680078BACKGROUND

  • 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.

    PMID: 14401357BACKGROUND

  • 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.

    PMID: 5818715BACKGROUND

  • 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.

    PMID: 16170253BACKGROUND

  • 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.

    PMID: 2861102BACKGROUND

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

    PMID: 3280212BACKGROUND

  • 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.

    PMID: 6196112BACKGROUND

  • 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.

    PMID: 19556187BACKGROUND

  • 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.

    PMID: 1337136BACKGROUND

  • 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.

    PMID: 1681331BACKGROUND

  • 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.

    PMID: 8556729BACKGROUND

  • 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.

    PMID: 3203176BACKGROUND

  • 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.

    PMID: 11807342BACKGROUND

  • 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.

    PMID: 10507453BACKGROUND

  • 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.

    PMID: 10579658BACKGROUND

  • 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.

    PMID: 7874096BACKGROUND

  • 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.

    PMID: 9653525BACKGROUND

Related Links

MeSH Terms

Conditions

AggressionBrain Injuries, TraumaticBrain Injuries

Interventions

Amantadine

Condition Hierarchy (Ancestors)

Aberrant Motor Behavior in DementiaBehavioral SymptomsBehaviorSocial BehaviorBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesCraniocerebral TraumaTrauma, Nervous SystemWounds and Injuries

Intervention Hierarchy (Ancestors)

AdamantaneBridged-Ring CompoundsHydrocarbons, CyclicHydrocarbonsOrganic Chemicals

Study Officials

  • Flora M Hammond, M.D.

    Carolinas Rehabilitation

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 21, 2008

First Posted

February 29, 2008

Study Start

March 1, 2003

Primary Completion

November 1, 2007

Study Completion

November 1, 2007

Last Updated

April 25, 2022

Record last verified: 2008-02