A Randomized, Double-Blind, Placebo-Controlled, Study to Evaluate the Preliminary Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of Bryostatin 1 in Patients With Alzheimer's Disease
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Number of Participants With Adverse Events as a Measure of Safety and Tolerability
研究概览
简要总结
This study is being done to evaluate the safety, tolerability and potential effectiveness of a new investigational drug, bryostatin 1, in patients with Alzheimer's disease (AD).
详细描述
This study is a single center, randomized, double-blind, placebo-controlled, parallel groups trial in patients with AD. Each subject enrolled in the trial will be randomized to receive a single IV dose of 0 (placebo) or 25 μg/m2 bryostatin. A total of 15 subjects (5 in the placebo arm and 10 in the treatment arm) will be enrolled in the study. The study consists of screening evaluations and on study evaluations divided into two segments, an inpatient segment and an outpatient segment. The four-day inpatient segment will consist of baseline evaluations and a 1-hour IV infusion of study drug followed by evaluations at multiple evaluations over the first 72 hrs post dose. During the outpatient segment, patients will be followed for AEs and have a final evaluation at 2 weeks post dose and a 4-week telephone safety follow up. Evaluations will include safety, efficacy, pharmacokinetics, and pharmacodynamics as assessed by PKC activity
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, age 50 - 85 yrs. Females are non-childbearing potential
- •Patient must have a cognitive deficit present for at least 1 year and meet diagnostic criteria for probable Alzheimer's Disease Dementia by NIA-AA criteria or prodromal Alzheimer's Disease
- •Mini Mental State Exam score of 16-26
- •Ability to walk, at least with an assistive device
- •Vision and hearing sufficient to comply with testing
- •Normal cognitive and social functioning prior to onset of dementia, with evidence of progressive symptoms from patient or informant
- •Consistent caregiver to accompany patient to visits
- •Sufficient basic education to be able to complete the cognitive assessments
- •Living outside an institution
排除标准
- •Dementia due to any condition other than AD, including vascular dementia
- •Significant neuroimaging abnormalities, previously known or discovered on screening MRI scan,
- •Evidence of clinically significant unstable cardiovascular, renal, hepatic, gastrointestinal, neurological, or metabolic disease within the past 6 months
- •Use of any drug within 14 days prior to randomization unless the dose of the drug and the condition being treated have been stable for at least 30 days and are expected to remain stable during the study
- •Use of tobacco products or nicotine-containing products within 3 months before Day 1
- •Use of high dose vitamin E, or valproic acid
- •Any medical or psychiatric condition that may require medication or surgical treatment during the study
- •Life expectancy less than 6 months
- •Use of an investigational drug within 2 months prior to the screening visit
- •Clinically significant neurological disease other than AD
- •Major depression, alcohol or drug dependence or suicidality
- •Psychotic episodes requiring hospitalization or antipsychotic therapy for more than 2 weeks within the past 10 years, not linked to AD
- •Agitation sufficient to preclude participation in this trial
- •Epilepsy or anti-epileptic drug therapy
- •Abnormal laboratory tests that might point to another etiology for dementia;
- •Acute or poorly controlled medical illness
- •Likelihood, according to clinical judgment, of being transferred to a nursing home within 6 months
研究组 & 干预措施
Bryostatin 1
single dose of 25 μg/m2 bryostatin, intravenous infusion over 1 hour
干预措施: Bryostatin 1 (Drug)
placebo
single dose of placebo, intravenous infusion over 1 hour
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
时间窗: Within 2 weeks of study drug dosing
Evaluate the safety and tolerability of bryostatin 1 (hereinafter referred to as bryostatin) in patients with Alzheimer's Disease (AD) following a single intravenous (IV) dose.
Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD
时间窗: 48 hours post start of study drug infusion
Hopkins Verbal Learning Test - Revised (HVLT-R) delayed recall; change from baseline. HVLT consists of a 12-item word list drawn from 3 semantic categories, presented in 3 learning trials. Score range = 0-12. The lower the number, the more impaired. Repeatable Battery of Assessments for Neuropsychological Status (RBANS) figure recall; change from baseline. Total Score Range: 0-20. Each portion of the drawing is scored 1 point for correctness and completeness and 1 point for being placed properly in relation to the rest of the drawing. Drawing and placement scores are summed for the item total. To obtain subtest total score, the drawing and placement scores are summed for each item. The lower the number, the more impaired.
次要结局
- Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD(Specified timepoints within 2 weeks post study drug infusion)