The Effects of Rosiglitazone in Patients with MCI

描述（由申请方提供）：拟定的安慰剂对照临床试验将检验罗格列酮（一种具有胰岛素增敏和抗炎特性的过氧化物酶体增殖物激活受体-γ（PPAR-gamma）激动剂）改善遗忘型轻度认知障碍（MCI）患者记忆力的假设。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接受一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）结构的萎缩率。一部分受试者将在治疗前后接受腰椎穿刺，以确定罗格列酮是否影响与AD相关的脑脊液（CSF）生物标志物水平。这项试验将提供关于改善胰岛素敏感性、降低外周胰岛素水平和减少炎症对遗忘型MCI（阿尔茨海默病（AD）的可能前驱期）的认知功能和生物标志物的影响的有价值的数据。最重要的是，这项试验将阐明一种可能预防或推迟AD发作的新型治疗方法的可行性和潜在疗效。在这样做的过程中，我们将为未来全面的PPAR-gamma激动剂临床试验奠定基础。

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.