Amantadine for the Treatment of Traumatic Brain Injury Irritability and Aggression: A Multi-site Study
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Purpose
The purpose of this study is to study the effect of amantadine on irritability and aggression caused by traumatic brain injury.
| Condition | Intervention |
|---|---|
|
Brain Injury Aggression |
Drug: Amantadine Hydrochloride Drug: Placebo |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | A Multi-Center, Parallel-Group, Randomized, Double-Blind, Placebo-Controlled Trial of Amantadine Hydrochloride in the Treatment of Chronic Traumatic Brain Injury Irritability and Aggression: A Replication Study |
- Neuropsychiatric Inventory Irritability Domain [ Time Frame: 28 days ] [ Designated as safety issue: No ]
- Neuropsychiatric Inventory Aggression Domain [ Time Frame: 28 days and 60 days ] [ Designated as safety issue: No ]
- State Anger Aggression Expression Inventory -- II [ Time Frame: 28 and 60 days ] [ Designated as safety issue: No ]
- Neuropsychiatric Inventory Irritability Domain [ Time Frame: 60 days ] [ Designated as safety issue: No ]
- Neuropsychiatric Inventory Caregiver Distress Score for Irritability and Aggression Domains [ Time Frame: 28 and 60 days ] [ Designated as safety issue: No ]
- Clinical Global Impressions [ Time Frame: 28 and 60 days ] [ Designated as safety issue: No ]
- Global Impression of Change [ Time Frame: 28 and 60 days ] [ Designated as safety issue: No ]
- Short Form-12 [ Time Frame: 28 and 60 days ] [ Designated as safety issue: No ]
- Glasgow Coma Scale - Extended [ Time Frame: 28 and 60 days ] [ Designated as safety issue: No ]
- Satisfaction With Life Scale [ Time Frame: 28 and 60 days ] [ Designated as safety issue: No ]
- Patient Health Questionnaire - 9 [ Time Frame: 28 and 60 days ] [ Designated as safety issue: No ]
- Beck Depression Inventory II [ Time Frame: 28 and 60 days ] [ Designated as safety issue: No ]
- Fatigue Impact Scale [ Time Frame: 28 and 60 days ] [ Designated as safety issue: No ]
- Family Assessment Device General Functioning Scale [ Time Frame: 28 and 60 days ] [ Designated as safety issue: No ]
- Neuropsychologic tests [ Time Frame: 28 and 60 days ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 168 |
| Study Start Date: | August 2009 |
| Estimated Study Completion Date: | June 2013 |
| Estimated Primary Completion Date: | June 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Amantadine
Amantadine 100 mg every morning and Noon
|
Drug: Amantadine Hydrochloride
100 mg every morning and noon
Other Name: Symmetrel
|
|
Placebo Comparator: Placebo
Placebo tablets
|
Drug: Placebo
one placebo tablet every morning and 12 Noon
|
Detailed Description:
PURPOSE OF PROJECT: To study the effect of amantadine 100 mg administered twice daily compared to placebo on irritability from baseline to treatment Day 28.
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.
Eligibility| Ages Eligible for Study: | 16 Years to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Closed head injury (defined as impaired brain function resulting from externally inflicted trauma without penetrating injury) at least 6 months prior to enrollment
- Age at time of enrollment: 16 to 65 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:
- Previous participation in the CTBIRRS amantadine irritability study
- 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 neuroleptic agents or phenelzine
- History of schizophrenia or psychosis
- Suicidal ideation
- Diagnosis of progressive or additional neurologic disease
- Previous allergy or adverse reaction to amantadine hydrochloride
Contacts and Locations| Contact: Flora M Hammond, MD | 704-355-9330 | flora.hammond@carolinashealthcare.org |
| Contact: Marybeth Whitney, RN | 704-355-1409 | marybeth.whitney@carolinashealthcare.org |
| United States, Indiana | |
| Indiana University and the Rehabilitation Hospital of Indiana | Recruiting |
| Indianapolis, Indiana, United States, 46254 | |
| Contact: Flora Hammond, MD flora.hammond@rhin.com | |
| Contact: Elena Gillespie 317-329-2212 elene.gillespie@rhin.com | |
| Principal Investigator: Flora Hammond, MD | |
| United States, Massachusetts | |
| Spaulding Rehabilitation | Recruiting |
| Boston, Massachusetts, United States, 02114 | |
| Contact: Ross Zafonte, DO RZAFONTE@PARTNERS.ORG | |
| Principal Investigator: Ross Zafonte, DO | |
| United States, North Carolina | |
| Carolinas Rehabilitation | Recruiting |
| Charlotte, North Carolina, United States, 28203 | |
| Contact: Marybeth Whitney, R.N. 704-355-1409 marybeth.whitney@carolinashealthcare.org | |
| Contact: Flora Hammond, M.D. 704-355-9330 flora.hammond@carolinashealthcare.org | |
| Principal Investigator: Flora M Hammond, M.D | |
| Sub-Investigator: Lori M Grafton, M.D. | |
| Sub-Investigator: Shilpa Kasuganti, MD | |
| Sub-Investigator: Jennifer Camp, MD | |
| United States, Ohio | |
| The Ohio State University | Not yet recruiting |
| Columbus, Ohio, United States, 43210 | |
| Contact: Jerry Mysiw, MD | |
| Principal Investigator: Jerry Mysiw, MD | |
| United States, Texas | |
| TIRR Memorial Herman | Recruiting |
| Houston, Texas, United States, 77030 | |
| Contact: Mark Sherer, PhD 713-799-7007 Mark.Sherer@memorialhermann.org | |
| Principal Investigator: Mark Sherer, PhD | |
| Sub-Investigator: Monika Shah, MD | |
| United States, Washington | |
| University of Washington | Recruiting |
| Seattle, Washington, United States, 98195 | |
| Contact: Kathy Bell, MD 206-685-0935 krbell@u.washington.edu | |
| Contact: Leslie Kempthorne 206-543-0219 ette@u.washington.edu | |
| Principal Investigator: Kathy Bell, MD | |
| Sub-Investigator: Sureyya Dikmen, PhD | |
| Principal Investigator: | Flora M Hammond, MD | Carolinas Rehabilitation |
More Information
Additional Information:
No publications provided
| Responsible Party: | Carolinas Healthcare System |
| ClinicalTrials.gov Identifier: | NCT00779324 History of Changes |
| Other Study ID Numbers: | 09-08-11B, NIDRR H133A080035 |
| Study First Received: | October 23, 2008 |
| Last Updated: | February 10, 2012 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by Carolinas Healthcare System:
|
traumatic brain injury irritability aggression amantadine behavior |
Additional relevant MeSH terms:
|
Aggression Brain Injuries Behavioral Symptoms Brain Diseases Central Nervous System Diseases Nervous System Diseases Craniocerebral Trauma Trauma, Nervous System Wounds and Injuries Amantadine Antiparkinson Agents Anti-Dyskinesia Agents Central Nervous System Agents |
Therapeutic Uses Pharmacologic Actions Antiviral Agents Anti-Infective Agents Dopamine Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents |
ClinicalTrials.gov processed this record on May 22, 2013