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.?