A Single Site, Randomized, Double-blind, Placebo Controlled Trial of NIC5-15 in Subjects With Alzheimer's Disease
Condition: Alzheimer's Disease; Dementia
MeSH terms: Alzheimer Disease; Dementia
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to evaluate the safety and efficacy of NIC5-15 in the treatment
      of Alzheimer's Disease.
    

Detailed description: 
      Recent epidemiologic evidence, has suggested that diabetes mellitus significantly increases
      risk for the development of Alzheimer's disease, independent of vascular risk factors.
      Moreover, even patients who are simply insulin resistant, without frank diabetes, have been
      shown to share this elevated risk for the development of AD. As insulin's role as a
      neuromodulator in the brain has been revealed, several potential mechanisms for the
      interaction of diabetes or insulin resistance with AD have been suggested such as decreased
      cortical glucose utilization particularly in the hippocampus and entorhinal cortex; increased
      oxidative stress through the formation of advanced glycation end products; increased Tau
      phosphorylation and neurofibrillary tangle formation; and increased beta-amyloid aggregation
      through inhibition of insulin-degrading enzyme. The future treatment of AD might involve
      pharmacologic and dietary manipulations of insulin and glucose regulation

      NIC5-15 is a single, small, naturally occurring molecule. Animal studies and some human
      trials have shown NIC5-15 to be safe and a potent insulin sensitizer at doses equivalent to
      800-2000mg per day. In preclinical studies at doses higher than those previously studied in
      clinical trials, we found that NIC5-15 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 Disease for two reasons:

      It is a -secretase inhibitor that is Notch-sparing. It is potentially an insulin-sensitizer.

      However critical safety and human efficacy studies must be conducted. This application
      proposes to conduct these early critical human studies. The goal of the studies contained in
      this proposal is to establish safety and efficacy of NIC5-15 for the treatment of AD. The
      specific objectives of this study are to:

      Specific Objective #1) Conduct a multiple dose safety study of NIC5-15 to establish safety in
      the doses that appear to block amyloid accumulation. These studies will characterize the
      safety profile, pharmacokinetics, and tolerability

      This objective was met with completion of the initial study ID#NCT00470418.

      The current study continues investigations of NIC5-15 in Alzheimer's disease with the
      following objective:

      Specific Objective #2) Conduct a double blind placebo controlled pilot efficacy study of
      NIC5-15 in patients with AD. The goals of this study are to:

      A) Demonstrate feasibility for a multi-site trial that will be used to guide the design of a
      future larger effort. Demonstration of feasibility will include examination of accrual rate,
      overall recruitment, adherence to protocol, compliance with medication and willingness to
      complete a randomized trial, and lack of short term toxicity.

      B) Collect preliminary evidence of efficacy in terms of cognitive and global measures as well
      as secondary efficacy outcomes of activities of daily living, behavioral disturbances and AD
      biomarkers.
    

Intervention name(s): Drug: NIC5-15; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): A natural product, found in many foods and plants with mild insulin sensitizing effects; Subjects with Alzheimer's Disease placebo comparator
Other intervention name(s): Pinitol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Alzheimer Disease; Alzheimer Type Senile Dementia; Alzheimer's Disease; clinical trial; dementia; diabetes; dietary supplements; Senile Dementia, Alzheimer; Therapeutics; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Delirium, Dementia, Amnestic, Cognitive; Disorders; Mental Disorders