Pilot studies of the nutritional supplement NIC5-15 in Alzheimers Disease

描述（由申请人提供）：NIC5-15是肌醇家族中的天然产物。它存在于许多食物和松树皮中。NIC5-15天然存在于许多食物中，是一种经批准的食品补充剂。在人体研究中，NIC5-15在800-2000mg的剂量下显示出胰岛素增敏作用。在临床前研究中，剂量高于目前批准的人类使用剂量，它会干扰β淀粉样蛋白的积累，这是阿尔茨海默病病理发展的重要一步。这些数据提示NIC5-15可能是治疗阿尔茨海默病的合理药物。然而，必须进行关键的安全性和人体功效研究。本申请建议利用西奈山综合临床研究中心的设施和资源进行这些早期关键的人体研究。提案中包含的研究目标是确定NIC5-15治疗AD的安全性和有效性。具体目的是：1)开展NIC5-15的多剂量安全性研究，以确定似乎可以阻断淀粉样蛋白积累的剂量的安全性；2)开展NIC5-15在AD患者中的双盲安慰剂对照先导疗效研究。这些研究将描述安全性、药代动力学，并检查对潜在的外周生物标志物（血浆和脑脊液a - β；脑脊液Tau）的影响。此外，在一部分受试者中，我们建议通过FDG PET扫描来检测NIC5-15对葡萄糖代谢率的影响。虽然资源不允许权力建立效力，但这项研究将用于证明多地点试验的可行性，并将用于指导未来更大努力的设计。可行性论证将包括确保招募和维持该方案受试者的能力、缺乏短期毒性、在认知功能和日常生活活动的次要结果、护理人员负担和生物标志物方面的潜在早期初步疗效证据。

DESCRIPTION (provided by applicant): NIC5-15 is a natural product in the family of inositols. It is found in many foods as well as pine tree bark. NIC5-15 is found naturally in many foods and is commercially available as an approved food supplement. NIC5-15 has been shown to have insulin-sensitizing effects in human studies at doses of 800-2000mg. In preclinical studies at doses higher than those currently approved for human use, it interferes with the accumulation of beta amyloid, an important step in the development of Alzheimer's pathology. These data suggest that NIC5-15 may be a reasonable therapeutic agent for the treatment of Alzheimer's Disease. However, critical safety and human efficacy studies must be conducted. This application proposes to conduct these early critical human studies, using the facilities and resources of the Mount Sinai General Clinical Research Center. The goal of the studies contained in the proposal is to establish safety and efficacy of NIC5-15 for the treatment of AD. The specific aims are to 1) conduct a multiple dose safety study of NIC5-15 to establish safety in the doses that appear to block amyloid accumulation; and 2) conduct a double blind placebo controlled pilot efficacy study of NIC5-15 in patients with AD. These studies will characterize the safety profile, pharmacokinetics, and examine the effect upon potential peripheral biomarkers (plasma and CSF A-beta; CSF Tau). In addition, in a subset of subjects, we propose to examine the effects of NIC5-15 upon glucose metabolic rate as reflected by FDG PET scanning. While resources will not permit power to establish efficacy, this study will be used to demonstrate feasibility for a multi-site trial and will be used to guide the design of a future larger effort. Demonstration of feasibility will include insuring ability to recruit and maintain subjects on the regimen, lack of short term toxicity, potential early preliminary evidence of efficacy in terms of cognitive function and secondary outcomes of activities of daily living, caregiver burden and biomarkers.