Tal Davidy , Iscka Yore , Tali Cukierman-Yaffe , Ramit Ravona-Springer , Abigail Livny , Orit H. Lesman-Segev , Yossi Azuri , Owen Carmichael , Dimitrios Kapogiannis , Henrik Zetterberg , HungMo Lin , Mary Sano , Michal Schnaider Beeri
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Since both INI and </span></span>dulaglutide<span> have beneficial effects on the cerebrovascular disease (CVD), we anticipate that improved CVD will underlie the hypothesized cognitive benefits.</span></span></p></div><div><h3>Methods</h3><p>This 12-months trial will include 80 older adults aged > 60 with MetS and MCI, randomized to 4 groups: INI/oral semaglutide, intranasal placebo/oral semaglutide, INI/oral placebo<span>, and intranasal placebo/oral placebo. Feasibility of combining INI with semaglutide will be tested by examining the ease of use of INI (20IU, twice/day) with semaglutide (14 once daily), adherence, and safety profile are the efficacy of combination therapy on global cognition and neurobiological markers: cerebral blood flow, cerebral glucose utilization<span>, white matter hyperintensities, Alzheimer’s related blood biomarkers and expression of insulin signaling proteins measured in brain-derived exosomes. 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引用次数: 0
摘要
引言我们介绍了一项双盲安慰剂对照可行性试验的原理和设计，该试验将鼻内胰岛素（INI）与 GLP-1 受体激动剂塞马鲁肽（semaglutide）相结合，以改善患有代谢综合征（MetS）和轻度认知障碍（MCI）的老年人的认知能力。由于INI和度拉鲁肽对脑血管疾病（CVD）都有益处，我们预计CVD的改善将是假设的认知益处的基础：INI/口服塞马鲁肽、鼻内安慰剂/口服塞马鲁肽、INI/口服安慰剂和鼻内安慰剂/口服安慰剂。将通过研究 INI（20IU，2 次/天）与塞马鲁肽（14 次/天）的易用性、依从性和安全性，测试 INI 与塞马鲁肽联合治疗的可行性，以及联合治疗对整体认知和神经生物学标志物的疗效：脑血流量、脑葡萄糖利用率、白质高密度、阿尔茨海默氏症相关血液生物标志物和脑源性外泌体中测量的胰岛素信号蛋白的表达。这项可行性研究预计将为多中心大规模随机临床试验（RCT）奠定基础，该试验将评估胰岛素诱导的心血管疾病和痴呆症高危人群联合使用semaglutide对认知的益处。
A feasibility study of the combination of intranasal insulin with oral semaglutide for cognition in older adults with metabolic syndrome at high dementia risk- Study rationale and design
Introduction
We present the rationale and design of a double-blind placebo-controlled feasibility trial combining intranasal insulin (INI) with semaglutide, a GLP-1 receptor agonist, to improve cognition in older adults with metabolic syndrome (MetS) and mild cognitive impairment (MCI). Since both INI and dulaglutide have beneficial effects on the cerebrovascular disease (CVD), we anticipate that improved CVD will underlie the hypothesized cognitive benefits.
Methods
This 12-months trial will include 80 older adults aged > 60 with MetS and MCI, randomized to 4 groups: INI/oral semaglutide, intranasal placebo/oral semaglutide, INI/oral placebo, and intranasal placebo/oral placebo. Feasibility of combining INI with semaglutide will be tested by examining the ease of use of INI (20IU, twice/day) with semaglutide (14 once daily), adherence, and safety profile are the efficacy of combination therapy on global cognition and neurobiological markers: cerebral blood flow, cerebral glucose utilization, white matter hyperintensities, Alzheimer’s related blood biomarkers and expression of insulin signaling proteins measured in brain-derived exosomes. Efficacy will be assessed for the intent-to-treat sample.
Discussion
This feasibility study is anticipated to provide the basis for a multi-center large-scale randomized clinical trial (RCT) of the cognitive benefits of the combination of INI with semaglutide in individuals enriched for CVD and at high dementia risk.
期刊介绍：
Mechanisms of Ageing and Development is a multidisciplinary journal aimed at revealing the molecular, biochemical and biological mechanisms that underlie the processes of aging and development in various species as well as of age-associated diseases. Emphasis is placed on investigations that delineate the contribution of macromolecular damage and cytotoxicity, genetic programs, epigenetics and genetic instability, mitochondrial function, alterations of metabolism and innovative anti-aging approaches. For all of the mentioned studies it is necessary to address the underlying mechanisms.
Mechanisms of Ageing and Development publishes original research, review and mini-review articles. The journal also publishes Special Issues that focus on emerging research areas. Special issues may include all types of articles following peered review. Proposals should be sent directly to the Editor-in-Chief.
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