A Single Site, Randomized, Double-blind, Placebo Controlled Trial of NIC5-15 in Subjects With Alzheimer's Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Change in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog)Score
研究概览
简要总结
The purpose of this study is to evaluate the safety and efficacy of NIC5-15 in the treatment of Alzheimer's Disease.
详细描述
Recent epidemiologic evidence, has suggested that diabetes mellitus significantly increases risk for the development of Alzheimer's disease, independent of vascular risk factors. Moreover, even patients who are simply insulin resistant, without frank diabetes, have been shown to share this elevated risk for the development of AD. As insulin's role as a neuromodulator in the brain has been revealed, several potential mechanisms for the interaction of diabetes or insulin resistance with AD have been suggested such as decreased cortical glucose utilization particularly in the hippocampus and entorhinal cortex; increased oxidative stress through the formation of advanced glycation end products; increased Tau phosphorylation and neurofibrillary tangle formation; and increased beta-amyloid aggregation through inhibition of insulin-degrading enzyme. The future treatment of AD might involve pharmacologic and dietary manipulations of insulin and glucose regulation
NIC5-15 is a single, small, naturally occurring molecule. Animal studies and some human trials have shown NIC5-15 to be safe and a potent insulin sensitizer at doses equivalent to 800-2000mg per day. In preclinical studies at doses higher than those previously studied in clinical trials, we found that NIC5-15 interferes with the accumulation of beta amyloid, an important step in the development of Alzheimer's pathology. These data suggest that NIC5-15 may be a reasonable therapeutic agent for the treatment of Alzheimer Disease for two reasons:
It is a -secretase inhibitor that is Notch-sparing. It is potentially an insulin-sensitizer.
However critical safety and human efficacy studies must be conducted. This application proposes to conduct these early critical human studies. The goal of the studies contained in this proposal is to establish safety and efficacy of NIC5-15 for the treatment of AD. The specific objectives of this study are to:
Specific Objective #1) Conduct a multiple dose safety study of NIC5-15 to establish safety in the doses that appear to block amyloid accumulation. These studies will characterize the safety profile, pharmacokinetics, and tolerability
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 95 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •NINCDS/ADRDA criteria for probable AD
- •MMSE between 12-27
- •Treatment with a cholinesterase inhibitor or an NMDA (N-methyl-D-asparate) antagonist with stable dose for at least 12 weeks
- •Home monitoring available for supervision of medications
- •Caregiver available to accompany patient to all visits and willing to participate in study as informant
- •Fluent in English or Spanish
- •Medical stability for this study as confirmed by review of records, internist's physical exam, neurological exam, and laboratory tests
- •Stable doses of non-excluded medication
- •No evidence of hepatic insufficiency
- •Able to swallow oral medications
- •Ability to participate in the informed consent process
排除标准
- •History of Diabetes Mellitus (OGTT criteria) requiring treatment with an excluded antidiabetic medication (see below) or history of hypoglycemia
- •Active hepatic or renal disease
- •Cardiac disease including history of congestive heart failure or current treatment for CHF; history of recent myocardial infarction
- •Use of another investigational drug within the past two months
- •History of clinically significant stroke
- •History of seizure or head trauma with disturbance of consciousness within the past two years
- •Major mental illness including psychotic disorders, bipolar disorder, or major depressive episode within the past two years Medication Exclusion
- •Current use of oral hypoglycemic agents including sulfonylureas and meglintinides
- •Current or past treatment with insulin for longer than two weeks
- •Current use of drugs with significant anticholinergic or antihistaminic properties
研究组 & 干预措施
Placebo
Subjects with Alzheimer's Disease Intervention: Drug: Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog)Score
时间窗: Over 6 months, measured at visits 2 (week 2), 6 (week 12), 8 (week 24)
A psychometric instrument that evaluates memory, attention, reasoning, language, orientation, and praxis.
次要结局
- APO-E genotyping(Collected at visit 2 (week 2))
- Change in Alzheimer's Disease Cooperative Study Clinician's Global Impression of Change (ADCS-CCGIC) Score(Over 6 months, measured at visits 2 (week 2), 6 (week 12), 8 (week 24))
- Change in Neuropsychiatric Inventory (NPI) Score(Over 6 months, measured at visits 2 (week 2), 6 (week 12), 8 (week 24))
- Changes in AD Biomarkers(Blood collected at visits 2 (week 2), 6 (week 12), 8 (week 24))
- Change in Mini-Mental State Examination (MMSE) Score(Over 6 months, measured at visits 2 (week 2), 6 (week 12), 8 (week 24))
- Change in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) Score(Over 6 months, measured at visits 2 (week 2), 6 (week 12), 8 (week 24))