Improving Beta-2 Adrenergic Signaling in Alzheimer's Disease
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Cognition Evaluation
研究概览
简要总结
The purpose of this study is to test the effects of long-term therapeutic doses of formoterol, on a) cerebrospinal fluid (CSF) tau levels, and Amyloid Beta protein 40/42 levels in the CSF, and b) cognitive function in people with mild to moderate Alzheimer' Disease (AD).
详细描述
The purpose of this study is to test the effects of long-term therapeutic doses of formoterol, on a) cerebrospinal fluid CSF tau levels, and A-beta amyloid protein 40/42 levels, and b) cognitive function: NE-ergic neurons undergo significant degeneration in AD. This system plays a significant role in cognition. Recent studies have indicated that increasing NE levels in the brain would significantly improve microglia migration and clearance of A-beta amyloid protein 40/42 levels in mouse models of AD. The investigators plan to test whether long- term daily treatment with inhaled formoterol solution would improve the structure and function of hippocampal neurons in AD. Study Design: Randomization and initiation of experimental treatment: All participants will be given formoterol daily for 52 weeks. The active regimen will be initiated as (20 micro gram, BID). The dose will be decreased if there is evidence of side effects, including cardiac or respiratory alteration changes, gastro-intestinal disturbances or neurological issues.
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
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females between the ages of 50-85,
- •Mild-to-moderate AD (NINCDS/ADRDA criteria for probable AD will be used to establish AD diagnosis).
- •MMSE 16-26.
排除标准
- •Non-AD dementia or significant neurological disease such as Parkinson's disease, stroke, brain tumor,multiple sclerosis, seizure disorder, focal brain lesion, or head injury with loss of consciousness.
- •Hypothyroidism, congestive heart failure (New York Heart Association Class III or IV), significant extrapyramidal symptoms on neurological examination, serum creatinine>1.3 mg/dl, significant arrhythmias or conduction defect abnormalities on ECG,
- •Use of another beta2 adrenergic drug within the last 2 months.
- •Residence in a long-term care facility.
- •Evidence of any significant clinical disorder or laboratory finding that renders the person unsuitable for receiving an investigational new drug.
- •Known hypersensitivity or prior exposure to formoterol.
- •Active asthma or family history of asthma.
研究组 & 干预措施
Formoterol A
12 months, formoterol, 20microgram/2ml, inhaler, BID
干预措施: Formoterol A (Drug)
Formoterol B
12 months, normal saline, 2ml, inhaler, BID
干预措施: Formoterol B (placebo) (Other)
结局指标
主要结局
Cognition Evaluation
时间窗: 1 Month
Participants will be administered the CANTAB every month for 16 months
Brain-derived neurotrophic factor (BDNF) Evaluation
时间窗: Baseline and month 16
Samples of Plasma and Cerebral Spinal Fluid Biomarkers will be taken at baseline and month 16
次要结局
- Amyloid accumulation(Baseline and month 16)
研究者
J. Wesson Ashford
Clinical Professor
VA Palo Alto Health Care System