Pilot studies of the nutritional supplement d-pinitol in Alzheimer's Disease

营养补充剂 d-松醇治疗阿尔茨海默病的初步研究

• 批准号: 7148117
• 负责人: HILLEL GROSSMAN
• 金额: $ 33.9万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-30 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7148117
• 关键词: Alzheimer' s disease; aspartic endopeptidases; biomarker; clinical research; food; glucose; human; insulin; pathology

DESCRIPTION (provided by applicant): D-pinitol is a natural product in the family of inositols. It is found in many foods as well as pine tree bark. D-pinitol is found naturally in many foods and is commercially available as an approved food supplement. D-pinitol 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 d-pinitol 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 d-pinitol for the treatment of AD. The specific aims are to 1) conduct a multiple dose safety study of d-pinitol to establish safety in the doses that appear to block amyloid accumulation; and 2) conduct a double blind placebo controlled pilot efficacy study of d-pinitol 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 d-pinitol 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.

描述（由申请人提供）：D-松醇是肌醇家族中的天然产物。它存在于许多食物以及松树皮中。D-松醇天然存在于许多食物中，并可作为批准的食品补充剂在商业上获得。在人体研究中，D-松醇在800- 2000毫克的剂量下显示出胰岛素增敏作用。在临床前研究中，剂量高于目前批准用于人类的剂量，它干扰β淀粉样蛋白的积累，这是阿尔茨海默病病理学发展的重要步骤。这些数据表明，d-松醇可能是一个合理的治疗剂，用于治疗阿尔茨海默病。然而，必须进行关键的安全性和人体功效研究。本申请建议使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人体研究。 该提案中包含的研究目标是确定d-松醇治疗AD的安全性和有效性。具体目的是：1）进行d-松醇的多剂量安全性研究，以确定似乎阻断淀粉样蛋白蓄积的剂量的安全性; 2）在AD患者中进行d-松醇的双盲安慰剂对照初步疗效研究。这些研究将描述安全性特征、药代动力学，并检查对潜在外周生物标志物（血浆和CSF A-β; CSF Tau）的影响。此外，在受试者的一个子集，我们建议检查D-松醇对葡萄糖代谢率的影响，反映了FDG PET扫描。虽然资源不允许确定疗效，但本研究将用于证明多中心试验的可行性，并将用于指导未来更大规模试验的设计。可行性的证明将包括确保招募和维持方案受试者的能力，缺乏短期毒性，在认知功能和日常生活活动的次要结局、护理人员负担和生物标志物方面的有效性的潜在早期初步证据。