A Prospective, Randomized, Multi-Center, Double-Blind, 26 Week, Placebo-Controlled Trial of Memantine (10mg BID) for the Frontal and Temporal Subtypes of Frontotemporal Dementia
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 81
- 试验地点
- 9
- 主要终点
- Change in Neuropsychiatric Inventory (NPI)
研究概览
简要总结
The primary objective of the study is to determine whether memantine is effective in slowing the rate of behavioral decline in frontotemporal dementia.
The secondary objective of the study is to assess the safety and tolerability of long-term treatment with memantine in patients with frontotemporal dementia (FTD) or semantic dementia (SD). To determine whether memantine is effective in slowing the rate of cognitive decline in frontotemporal dementia. To evaluate whether memantine delays or decreases the emergence of parkinsonism in frontotemporal dementia.
The tertiary objective of the study is to determine whether treatment with memantine affects changes in weight
详细描述
This is a multicenter, randomized, double-blind, placebo-controlled trial of memantine 10 mg twice daily versus placebo, at a ratio of 1:1, to receive active drug or placebo. Screening and enrollment is planned to last approximately one year. A Data and Safety Monitoring Board, consisting of a clinical pharmacist and 3 neurologists will review all AE reports approximately every 3 months after study initiation. The DSMB will notify the principal investigator, the study sponsor and the CHR if significant concerns are raised by their review of the AE data. An interim analysis of efficacy data will be conducted after 50% of the targeted enrollment population has completed 26 weeks of drug treatment.
Including screening and off-drug follow up, each subject will participate in the study for approximately 34 weeks.
The entire study is anticipated to last 86 weeks if enrollment is completed within one year of study initiation.
The targeted enrollment is 140.
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
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A subject must meet ALL of the following criteria to be considered for enrollment in this study:
- •Signed and dated written informed consent obtained from the subject and the subject's caregiver in accordance with local IRB regulations.
- •Must meet criteria Neary et al. criteria for frontotemporal dementia (FTD) or semantic dementia (SD)
- •CT or MRI of brain within 12 months consistent with a diagnosis of FTD or SD.
- •MMSE ≥ 15 at screening visit.
- •Judged by investigator to be able to comply with neuropsychological evaluation at baseline.
- •Must have reliable caregiver accompany subject to all study visits. Caregiver must read, understand and speak English fluently in order to ensure comprehension of informed consent form and informant-based assessments of subject. Caregiver must also have frequent contact with subject (at least 3 times per week for one hour) and be willing to monitor study medication compliance and the subject's health and concomitant medications throughout the study.
- •In the opinion of the investigator, the patient and the caregiver will be compliant with the protocol and have a high probability of completing the study.
排除标准
- •Any one of the following will exclude a subject from being enrolled into the study:
- •Insufficient fluency in English to complete neuropsychological and functional assessments.
- •Concurrent Motor Neuron Disease judged by investigator to have bulbar or upper extremity impairments at baseline that would interfere with neuropsychological assessment, or that are expected to lead to such impairments within one month.
- •Exclusion criteria as listed in Neary criteria. Diagnosis of progressive nonfluent aphasia by Neary criteria.
- •Use of memantine within 4 weeks prior to randomization.
- •Evidence of other neurological or psychiatric disorders which preclude diagnosis of FTD (including, but not limited to, stroke, Parkinson's disease, any psychotic disorder, severe bipolar or unipolar depression, seizure disorder, or head injury with loss of consciousness) within the past year.
- •Concurrent treatment with acetylcholinesterase inhibitors, antipsychotic agents, mood stabilizers (valproate or lithium) or benzodiazepines (other than temazepam or zolpidem), or use of any of these agents within 4 weeks prior to randomization. Atypical antipsychotic agents may be started after the baseline visit if felt to be medically necessary by the investigator and will be recorded as a secondary outcome measure.
- •History of alcohol or substance abuse within 1 year prior to screening, if deemed clinically significant by investigator.
- •Any current malignancy, or any clinically significant hematological, endocrine, cardiovascular, renal, hepatic, gastrointestinal or neurological disease. If the condition has been stable for at least the past year and is judged by the investigator not to interfere with the patient's participation in the study, the patient may be included.
- •Clinically significant lab abnormalities at screening, including Creatinine ≥ 1.7, B12 below laboratory normal reference range or TSH above site's laboratory normal reference range. Subjects with abnormal B12 or TSH levels at screening may be included per investigator's discretion.
- •CT or MRI evidence of any of the following: hydrocephalus, stroke, space-occupying lesion, cerebral infection or any clinically significant CNS disease other than FTD.
- •10.Systolic blood pressure greater than 180 or less than 90 mm Hg. Diastolic blood pressure greater than 105 or less than 50 mm Hg.
- •Abnormal ECG at screening judged to be clinically significant by the investigator.
- •Use of investigational drugs or participation in investigational drug study within 60 days of screening.
研究组 & 干预措施
1
Memantine 10mg BID
干预措施: memantine (Drug)
2
Placebo condition
干预措施: Placebo pill (Drug)
结局指标
主要结局
Change in Neuropsychiatric Inventory (NPI)
时间窗: Baseline, 26 weeks
NPI:12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating, nighttime behavior. A screening question is asked about each sub-domain. If the responses to these questions indicate that the patient has problems with a particular sub-domain of behavior, the caregiver is only then asked all the questions about that domain, rating the frequency of the symptoms on a 4-point scale, their severity on a 3-point scale, and the distress the symptom causes them on a 5-point scale. Severity(1=Mild to 3=Severe),frequency(1=occasionally to 4=very frequently) scales recorded for each domain; frequency\*severity=each domain score(range 0-12). Total score=sum of each domain score(range 0-144);higher score=greater behavioral disturbances;negative change score from baseline=improvement.
Clinical Global Impression of Change (CGIC)
时间窗: 26 Weeks
The scale is rated on a 7-point scale, using a range of responses from 1 (very much improved) through 7 (very much worse). The clinician compares the participant's current condition to the condition at admission to the project.
次要结局
- Longitudinal Changes From Baseline to 26 Weeks for Test Battery: CDR-SB, FAQ, TFLS, MMSE, EXIT25, UPDRS, Boston Naming Test(Baseline and 26 Weeks)
- Longitudinal Changes From Baseline to 26 Weeks for Test Battery: Letter Fluency, Category Fluency, Digit Symbol, Digits Backwards(Baseline and 26 Weeks)
- Number of Participants Starting Antipsychotic Therapy(26 weeks)