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: 7447321
• 负责人: HILLEL GROSSMAN
• 金额: $ 16.13万
• 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 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7447321
• 关键词: AP40; Accounting; Activities of Daily Living; Adherence; Advanced Glycosylation End Products; Alzheimer' s Disease; Amyloid; Amyloid Proteins; Amyloid beta-Protein; Animals; Behavioral; Biological Factors; Biological Markers; Blood Vessels; Brain; Caregiver Burden; Cerebrum; Cessation of life; Cleaved cell; Clinical Research; Clinical Trials; Cognitive; Data; Dementia; Development; Diabetes Mellitus; Dose; Double-Blind Method; Drug Kinetics; Fabaceae; Family; Food; Food Supplements; Future; Glucose; Glycine max; Goals; Hippocampus (Brain); Human; Inositol; Insulin; Insulin Resistance; Insulinase; Measures; Metabolic; Minority; Monosaccharides; Neurofibrillary Tangles; Neuromodulator; Neurons; Outcome; Oxidative Stress; Pathology; Patients; Peptide Fragments; Peripheral; Pharmaceutical Preparations; Pilot Projects; Pinus (genus); Placebo Control; Plasma; Positron-Emission Tomography; Process; Protein Precursors; Protocol Compliance; Randomized Controlled Clinical Trials; Rate; Recruitment Activity; Research Personnel; Resources; Risk; Risk Factors; Role; Safety; Senile Plaques; Site; Soybeans; Therapeutic Agents; Therapeutic Human Experimentation; Toxic effect; Treatment Protocols; abeta accumulation; cerebrovascular; cognitive function; design; dietary supplements; entorhinal cortex; fluorodeoxyglucose positron emission tomography; human study; inhibitor/antagonist; insulin sensitizing drugs; neurofibrillary tangle formation; notch protein; pinitol; preclinical study; programs; secretase; tau Proteins; tau phosphorylation; theories; willingness

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.

描述（由申请人提供）：NIC 5 -15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。NIC 5 -15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，NIC 5 -15在800- 2000 mg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，NIC 5 -15可能是治疗阿尔茨海默病的合理治疗剂。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。提案中包含的研究目标是确定NIC 5 -15治疗AD的安全性和有效性。具体目的是1）进行NIC 5 -15的多次给药安全性研究，以确定似乎阻断淀粉样蛋白蓄积的剂量的安全性;和2）在AD患者中进行NIC 5 -15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中，我们建议检查NIC 5 -15对葡萄糖代谢率的影响，如FDG PET扫描所反映的。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。