The Effects of Rosiglitazone in Patients with MCI

描述(申请人提供)：拟议的安慰剂对照临床试验将测试罗格列酮的假设，即罗格列酮是一种具有胰岛素敏化和抗炎特性的过氧体增殖物激活受体-伽马(PPAR-伽马)激动剂，可以改善遗忘性轻度认知障碍(MCI)患者的记忆力。100名参与者将被随机分配接受18个月的罗格列酮或安慰剂治疗，每隔6个月进行一次认知评估。他们还将在治疗前和治疗结束时进行系列结构磁共振成像(MRI)，以确定罗格列酮是否改善支持记忆的内侧颞叶(MTL)结构的萎缩速度。一部分参与者将在治疗前和治疗后接受腰椎穿刺术，以确定罗格列酮是否影响与AD相关的生物标志物的脑脊液(CSF)水平。这项试验将提供有价值的数据，说明改善胰岛素敏感性、降低外周胰岛素水平和减少炎症对遗忘型MCI的认知功能和生物标记物的影响。遗忘型MCI可能是阿尔茨海默病(AD)的前驱阶段。最重要的是，这项试验将阐明一种可能预防或推迟AD发病的新疗法的可行性和潜在疗效。通过这样做，我们将为未来PPAR-伽马激动剂的全面临床试验奠定基础。

DESCRIPTION (provided by applicant): The proposed placebo-controlled clinical trial will test the hypothesis that rosiglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist with insulin-sensitizing and anti-inflammatory properties, improves memory in persons with amnestic mild cognitive impairment (MCI). One hundred participants will be randomly assigned to receive 18 months of treatment with rosiglitazone or placebo, with cognitive assessment at 6 month intervals. They will also undergo serial structural magnetic resonance imaging (MRI) prior to and at the end of treatment to determine whether rosiglitazone ameliorates the rate of atrophy in medial temporal lobe (MTL) structures supporting memory. A subset of participants will receive lumbar punctures before and following treatment to determine whether rosiglitazone affects cerebrospinal fluid (CSF) levels of biomarkers associated with AD. This trial will provide valuable data regarding the effects of improved insulin sensitivity, reduced peripheral insulin levels, and reduced inflammation on cognitive function and biological markers in amnestic MCI, a likely prodromal phase of Alzheimer's disease (AD). Most importantly, this trial will elucidate the feasibility and potential efficacy of a novel treatment that may prevent or postpone the onset of AD. In doing so, we will lay the groundwork for future full-scale clinical trials of PPAR-gamma, agonists.