Amantadine for the Treatment of Traumatic Brain Injury Irritability and Aggression: A Multi-site Study
NCT ID: NCT00779324
Last Updated: 2022-07-12
Study Results
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View full resultsBasic Information
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COMPLETED
NA
168 participants
INTERVENTIONAL
2009-08-31
2013-05-31
Brief Summary
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Detailed Description
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SUMMARY OF PROJECT: It is anticipated that 168 subjects with 168 corresponding subject informants will be recruited for the study. Carolinas Rehabilitation, the lead center, and 5 collaborating centers will enroll approximately 28 subjects each.
Subjects will be recruited primarily from the clinics. Also, letters will be sent to patients in our data base. If the first encounter with research personnel is by telephone, the research assistant will obtain verbal (telephone) consent from the subject's informant for the Neuropsychiatric Inventory (NPI) for subject irritability. The score on this questionnaire must be ≥ 6 for qualification. This allows pre-screening to take place and avoid an unnecessary clinic visit.
Subjects who consent and qualify will be randomized in a 1:1 ratio, amantadine to placebo. Stratification to randomization group will occur based on the presence of depression defined by a Beck's Depression Inventory-II (BDI-II) score ≥ 13. Randomized subjects will receive amantadine or placebo 100 mg twice daily every morning and 12 Noon. There will be 4 clinic visits. Visits will occur at baseline, for consenting and screening, day 28, day 60 and day 90. At all 4 clinic visits, both the subject and the informant will be given questionnaires regarding the subject's behavior and mood. Follow up phone calls will occur each week that the subject is not seen in the clinic until the end of the study. Follow up phone calls will assess for study medication compliance, adverse events and concomitant medication changes. Day 60 ends the period of the Randomized Clinical Trial phase of the study and the subjects will begin the 1 month continuation phase of the study when all participants receive active amantadine.
The following questionnaires will be used as measures of irritability for the subject and the informant: Neuropsychiatric Inventory (NPI), State Trait Anger Expression Inventory (STAXI-2), and Global Impression of Change.
The following questionnaires will be dispensed to the subject only: Short Form -12, Satisfaction With Life Scale, Patient Health Questionnaire, Beck Depression Inventory, Brief Symptom Inventory, Family Assessment Device, Fatigue Impact Scale, and tests of cognitive function. The Glasgow Outcome Score-Extended will be completed by the research assistant using information obtained primarily from the informant.
The Investigator will complete the Clinical Global Impression of change at Visits 1, 2, 3, and 4.
History and Physical Exam, creatinine level (kidney function) will be obtained for safety and tolerability. Serum pregnancy tests will be drawn at screening for females of childbearing potential.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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Amantadine
Amantadine 100 mg every morning and Noon
Amantadine Hydrochloride
100 mg every morning and noon
Placebo
Placebo tablets
Placebo
one placebo tablet every morning and 12 Noon
Interventions
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Amantadine Hydrochloride
100 mg every morning and noon
Placebo
one placebo tablet every morning and 12 Noon
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Irritability that is either new or worse than the level of irritability before the traumatic brain injury, by report of the Observer or person with TBI
* Age at time of enrollment: 16 to 75 years
* Voluntary informed consent and authorization of participant and informant
* Subject and informant willing to comply with the protocol
* Informant-rated NPI Irritability Domain score 6 or greater (moderate-to-severe irritability)
* 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 or during the 90-day participation
* No change in therapies or medications planned during the 90-day participation
* No surgeries planned during the 90-day participation
* Vision, hearing, speech, motor function, and comprehension sufficient to complete interviews
* Observer (e.g.: family member, close friend, employer) with whom subject interacts sufficiently to observe occurrences of irritability. The observer interacts with the participant for a period long enough and of a nature to be able to judge the participant's irritability. The interactions would need to be adequate to judge observer distress over the irritability, severity of irritability and frequency of irritability on the following scale: \< once weekly; once per week; several times per week, but not every day; essentially continuous.
Exclusion Criteria
* Ingestion of amantadine hydrochloride during the month prior to enrollment
* Potential subject without a reliable informant
* Penetrating head injury as defined by head injury due to gunshot, projectile or foreign object
* Injury \< 6 months prior to enrollment
* Inability to interact sufficiently for communication with caregiver
* Clinical signs of active infection
* Diagnosis of seizure in the month prior to enrollment
* Creatinine clearance \<60 mL/min
* Pregnancy (Beta-HCG + females of child-bearing potential) and lactating females
* Concurrent use of first generation neuroleptic agents or phenelzine
* History of schizophrenia or psychosis
* Active concern of schizophrenia or psychosis
* Diagnosis of progressive or additional neurologic disease that affects brain function, except stroke that occurs at th same time as the TBI
* Previous allergy or adverse reaction to amantadine hydrochloride
16 Years
75 Years
ALL
No
Sponsors
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Indiana University
OTHER
University of Washington
OTHER
The Institute for Rehabilitaion and Research Foundation
OTHER
Spaulding Rehabilitation Hospital
OTHER
Ohio State University
OTHER
Icahn School of Medicine at Mount Sinai
OTHER
Wake Forest University Health Sciences
OTHER
Responsible Party
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Principal Investigators
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Flora M Hammond, MD
Role: PRINCIPAL_INVESTIGATOR
Carolinas Rehabilitation
Locations
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Indiana University and the Rehabilitation Hospital of Indiana
Indianapolis, Indiana, United States
Spaulding Rehabilitation
Boston, Massachusetts, United States
Carolinas Rehabilitation
Charlotte, North Carolina, United States
The Ohio State University
Columbus, Ohio, United States
TIRR Memorial Herman
Houston, Texas, United States
University of Washington
Seattle, Washington, United States
Countries
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References
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Hammond FM, Sherer M, Malec JF, Zafonte RD, Dikmen S, Bogner J, Bell KR, Barber J, Temkin N. Amantadine Did Not Positively Impact Cognition in Chronic Traumatic Brain Injury: A Multi-Site, Randomized, Controlled Trial. J Neurotrauma. 2018 Oct 1;35(19):2298-2305. doi: 10.1089/neu.2018.5767. Epub 2018 Jun 7.
Hammond FM, Malec JF, Zafonte RD, Sherer M, Bogner J, Dikmen S, Whitney MP, Bell KR, Perkins SM, Moser EA. Potential Impact of Amantadine on Aggression in Chronic Traumatic Brain Injury. J Head Trauma Rehabil. 2017 Sep/Oct;32(5):308-318. doi: 10.1097/HTR.0000000000000342.
Hammond FM, Sherer M, Malec JF, Zafonte RD, Whitney M, Bell K, Dikmen S, Bogner J, Mysiw J, Pershad R; Amantadine Irritability Multisite Study Group. Amantadine Effect on Perceptions of Irritability after Traumatic Brain Injury: Results of the Amantadine Irritability Multisite Study. J Neurotrauma. 2015 Aug 15;32(16):1230-8. doi: 10.1089/neu.2014.3803. Epub 2015 Mar 31.
Related Links
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Carolinas Rehabilitation
Carolinas HealthCare System
Other Identifiers
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H133A080035
Identifier Type: OTHER_GRANT
Identifier Source: secondary_id
09-08-11B
Identifier Type: -
Identifier Source: org_study_id
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