A Pilot Study of Exendin-4 in Alzheimer s Disease
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 57
- 试验地点
- 1
- 主要终点
- Number of Participants With Incidence of Nausea
研究概览
简要总结
Background:
Exendin-4 (or Exenatide) is a medication currently used to treat diabetes that has shown promising results in animal and cellular models of Alzheimer's disease. It is possible that Exendin-4 may be a treatment for Alzheimer's disease, which involves the gradual deterioration and death of neurons. Researchers are interested in studying the safety and comparing the effects of Exendin-4 with placebo on cognitive performance, clinical progression of dementia, various chemicals measured in blood and cerebrospinal fluid, and brain MRI, in individuals with early-stage Alzheimer's disease or mild cognitive impairment.
Objectives:
To determine the safety and tolerability of twice daily administration of Exendin-4, as well as to acquire preliminary evidence for effects on cognitive performance, clinical progression of dementia, various chemicals measured in blood and cerebrospinal fluid, and brain MRI, in individuals with early-stage Alzheimer's disease or mild cognitive impairment.
Eligibility:
Individuals at least 60 years of age who have objective evidence of early-stage Alzheimer's disease or mild cognitive impairment in screening testing.
Design:
- Participants will be screened.
- Following the telephone screening, two in-person screening visits to determine eligibility.
- The screening visit will involve a medical history and neurological examination, tests of memory and cognition, a lumbar puncture, collection of blood and saliva samples, and brain Magnetic Resonance Imagine (MRI) studies. Participants will be required to appoint a Durable Power of Attorney for research and medical care during this protocol.
- Eligible participants will be divided into two groups (double-blind randomization). One group will receive Exendin-4 SC twice daily, and the other will receive a placebo. Participants will keep a medication diary and will be scheduled for additional study visits 1 and 2 weeks after the start of the treatment.
- Participants will have regular followup visits with blood tests, cognitive tests, imaging studies, and other examinations 6, 12, and 18 months after the start of the treatment. Another lumbar puncture may be performed optionally at the 18-month followup visit.
详细描述
Objective
Exendin-4 (or exenatide) is a medication currently used in the treatment of diabetes mellitus (DM). Exendin-4 has generated promising results as an agent protecting neurons from a number of assaults both in the laboratory and in studies on animals. Specifically, there is pre-clinical evidence that Exendin-4 may be a treatment for Alzheimer's disease (AD). Based on these facts, we conducted a pilot Phase II double blind randomized placebo-controlled clinical study to assess the safety and provide proof of concept for exendin-4 treatment in early Alzheimer's disease (AD), by demonstrating a response of disease biomarkers to the intervention. Our main hypothesis is that long-term administration of Exendin-4 in participants with amnestic MCI/early AD in FDA-approved doses is safe and will induce a change over time in AD biomarkers. Subject population: We intend to screen up to 100 potential participants in order to ensure that at least 40 participants (enrolled based on a clinical diagnosis of amnestic MCI/early AD and Cerebrospinal Fluid (CSF) biomarker evidence of AD) will be enrolled into treatment and complete the study. Design: Enrolled participants will be randomly assigned into one of two groups (Exendin-4 vs. Placebo) and will be followed at regular intervals for 18 months. Outcome measures: Safety and tolerability will be the primary outcomes. In addition, we will measure and assess the change over time of a number of exploratory outcomes with the intervention, including CSF and plasma biomarkers (such as CSF A42, tau, p181-tau and plasma A42/A40), cognitive performance measures (such as the Alzheimer's Disease Assessment scale, cognitive sub-scale, and other tests), clinical progression of dementia measures (such as the Clinical Dementia Rating scale sum-of-boxes), volumetric changes on structural brain MRI and changes in resting fMRI. All research will be performed on the National Institute on Aging (NIA) Clinical Research Unit located on the 5th floor of Harbor Hospital.
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)
盲法说明
Double-blind study with code kept by NIA Pharmacist who did not share with Investigators and had no interaction with participants and caregivers.
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Exendin-4
Exenatide 5 mcg or 10 mcg SC twice daily
干预措施: Exendin-4 SC (Drug)
Placebo
Placebo SC twice daily
干预措施: Placebo SC (Drug)
结局指标
主要结局
Number of Participants With Incidence of Nausea
时间窗: 18 months
Tolerability of exenatide (nausea is the most common expected adverse event of exenatide)
次要结局
- Mini Mental State Examination (MMSE)(18 months)
- Cerebrospinal Fluid Amyloid-beta 42 (CSF Abeta42)(18 months)
- Body Mass Index (BMI)(18 months)
- Alzheimer's Disease Assessment Scale-cognitive Subscale (ADAS-cog70)(18 months)
- Clinical Dementia Rating (CDR) Global Score(18 months)
- Clinical Dementia Rating (CDR) Sum of Boxes(18 months)
- Cerebrospinal Fluid (CSF) Total Tau(18 months)
- Cerebrospinal Fluid phospho181-tau (CSF p181-tau)(18 months)