艾塞那肽
医学
安慰剂
生物标志物
耐受性
临床试验
内科学
恶心
糖尿病
肿瘤科
药理学
2型糖尿病
不利影响
内分泌学
病理
替代医学
化学
生物化学
作者
Roger J. Mullins,Maja Mustapić,Chee W. Chia,Olga D. Carlson,Seema Gulyani,Joyce Tran,Yazhou Li,Mark P. Mattson,Susan M. Resnick,Josephine M. Egan,Nigel H. Greig,Dimitrios Kapogiannis
标识
DOI:10.2174/1567205016666190913155950
摘要
Background: Strong preclinical evidence suggests that exenatide, a glucagon-like peptide-1 (GLP- 1) receptor agonist used for treating type 2 diabetes, is neuroprotective and disease-modifying in Alzheimer’s Disease (AD). Objective: We performed an 18-month double-blind randomized placebo-controlled Phase II clinical trial to assess the safety and tolerability of exenatide and explore treatment responses for clinical, cognitive, and biomarker outcomes in early AD. Method: Eighteen participants with high probability AD based on cerebrospinal fluid (CSF) biomarkers completed the entire study prior to its early termination by the sponsor; partial outcomes were available for twentyone. Results: Exenatide was safe and well-tolerated, showing an expectedly higher incidence of nausea and decreased appetite compared to placebo and decreasing glucose and GLP-1 during Oral Glucose Tolerance Tests. Exenatide treatment produced no differences or trends compared to placebo for clinical and cognitive measures, MRI cortical thickness and volume, or biomarkers in CSF, plasma, and plasma neuronal extracellular vesicles (EV) except for a reduction of Aβ42 in EVs. Conclusion: The positive finding of lower EV Aβ42 supports emerging evidence that plasma neuronal EVs provide an effective platform for demonstrating biomarker responses in clinical trials in AD. The study was underpowered due to early termination and therefore we cannot draw any firm conclusions. However, the analysis of secondary outcomes shows no trends in support of the hypothesis that exenatide is diseasemodifying in clinical AD, and lowering EV Aβ42 in and of itself may not improve cognitive outcomes in AD.
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