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
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 168
- 试验地点
- 6
- 主要终点
- Proportion of Participants With >2-point Increase on Neuropsychiatric Inventory - Irritability Domain Rated by Observer Day 28
研究概览
简要总结
The purpose of this study is to study the effect of amantadine on irritability and aggression caused by traumatic brain injury.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 16 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Closed head injury (defined as impaired brain function resulting from externally inflicted trauma without penetrating injury) at least 6 months prior to enrollment
- •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.
排除标准
- •Previous participation in the Carolinas TBI Model System 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 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
研究组 & 干预措施
Amantadine
Amantadine 100 mg every morning and Noon
干预措施: Amantadine Hydrochloride (Drug)
Placebo
Placebo tablets
干预措施: Placebo (Drug)
结局指标
主要结局
Proportion of Participants With >2-point Increase on Neuropsychiatric Inventory - Irritability Domain Rated by Observer Day 28
时间窗: Day 28
The Neuropsychiatric Inventory (NPI) is a 40-item rating scale developed to assess 12 behavioral domains. Only the NPI-Irritability (NPI-I) domain was used for this study. NPI-I measures irritability with items including: bad temper, rapid mood changes, sudden anger, impatience, crankiness, argumentative. The rater selects the frequency (1-3) and severity (1-4) of the most problematic of these behavioral aspect(s) over the preceding month. The NPI score is the product of the frequency and severity for the NPI most problematic item score. The primary outcome measure was the proportion of participants with greater than two-point increase on the Neuropsychiatric Inventory Irritability domain. The total range is 1 (least irritability) - 12 (worst irritability).
次要结局
- Change in Neuropsychiatric Inventory - Irritability Domain Assessed by Participants Day 28(Day 28)
- Change in Neuropsychiatric Inventory - Irritability Domain Assessed by Participants Day 60(Day 60)
- Change in Neuropsychiatric Inventory - Irritability Domain Assessed by Observer Day 28(Day 28)
- Proportion of Participants With >2-point Increase on Neuropsychiatric Inventory - Irritability Domain Rated by Participant Day 28(Day 28)
- Clinical Global Impressions Day 60(60 days)
- Clinical Global Impressions Day 28(28 Days)
- Proportion of Participants With >2-point Increase on Neuropsychiatric Inventory Irritability Domain Rated by Observers Day 60(60 days)
- Proportion of Participants With >2-point Increase on Neuropsychiatric Inventory - Irritability Domain Rated by Participant Day 60(Day 60)
- Change in Neuropsychiatric Inventory - Irritability Domain Assessed by Observers Day 60(Day 60)