Network-Level Mechanisms for Preclinical Alzheimer's Disease Development
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Functional Connectivity Strengths of Neural Networks
研究概览
简要总结
The purpose of this project is to test the hypothesis that AGB101 low dose levetiracetam extended release formulation can reduce abnormal hyperfunctional activity in the hippocampus in normal, healthy adults. The investigators will compare the functional connectivity results after taking AGB101 or placebo.
详细描述
In this study the investigators want to find out whether the use of a perturbation, such as AGB101 low dose of levetiracetam extended release formulation, in healthy adults can reduce abnormal hippocampal network activity. The investigators also want to study whether this low dose of LEV can improve memory function.
Generic levetiracetam is a type of drug called an anti-epileptic or anti-seizure medication. It is FDA approved worldwide for adults and children as young as one month with seizures. It is a generic drug used in long-term epilepsy treatment. It is relatively safe and has an acceptable side-effect profile.
AGB101 has been developed as a novel extended release formulation of low dose levetiracetam (below clinically marketed doses for epilepsy) for slowing the progression of amnestic mild cognitive impairment.
It is known that age and the APOE 4 gene are important risk factors for late-onset Alzheimer's disease. Further studies have shown that cognitively normal, older adults have more hyperfunctional brain network activity, increased alpha beta accumulation, decreased memory function, and decreased brain volume, which is consistent with Alzheimer's disease patterns.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 55 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Fluent in English
- •At least eight (8) years of education
- •Geriatric Depression Scale (GDS) (62) score < 6
- •Hachinski Ischemic Score ≤ 4
- •Normal general cognitive function as well as 1) normal memory function, documented by MOCA score of 23 or greater, and a RBANS Delayed Memory Index score of 85 or greater.
排除标准
- •Neurological disease, such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or a history of significant head trauma or known structural brain abnormalities
- •Major psychiatric disease or chronic unstable medical conditions
- •History of drug abuse
- •History of alcohol abuse (4 or greater drinks per day on average)
- •Unable to complete MRI scans (no Pacemaker/Defibrillator)
- •Known clinically significant abnormalities in B12 or thyroid function tests
- •End Stage Renal Disease (ESRD)
- •Hemodialysis (HD)
研究组 & 干预措施
AGB101 220 mg, then Placebo
AGB101 220 mg/day capsule, once daily dosing for 2 weeks. After a 4 week washout, to be followed by Placebo, given as a capsule, once daily dosing for 2 weeks.
干预措施: AGB101 220 mg (Drug)
AGB101 220 mg, then Placebo
AGB101 220 mg/day capsule, once daily dosing for 2 weeks. After a 4 week washout, to be followed by Placebo, given as a capsule, once daily dosing for 2 weeks.
干预措施: Placebo (Other)
Placebo, then AGB101 220 mg
Placebo, given as a capsule, once daily for 2 weeks. After a 4 week washout, to be followed by AGB101 220 mg/day capsule, once daily dosing for 2 weeks.
干预措施: AGB101 220 mg (Drug)
Placebo, then AGB101 220 mg
Placebo, given as a capsule, once daily for 2 weeks. After a 4 week washout, to be followed by AGB101 220 mg/day capsule, once daily dosing for 2 weeks.
干预措施: Placebo (Other)
结局指标
主要结局
Functional Connectivity Strengths of Neural Networks
时间窗: 2 weeks after treatment between AGB101 and Placebo
The seed-based functional connectivity strengths of the hippocampus network and the default mode network will be employed to measure the changes between AGB101 and Placebo perturbation. The functional connectivity strengths will be measured with the median of the Pearson cross-correlation coefficients over entire brain regions.
次要结局
- Rey Auditory Verbal Learning Test (AVLT), Delayed Recall Scaled Integer. The Higher is the Better(Placebo vs AGB101 2 weeks after treatment paired t-test)
研究者
Yang Wang
Professor
Medical College of Wisconsin