Development of NIC5-15 in the Treatment of Alzheimer's Disease
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Development of NIC5-15 in the Treatment of Alzheimer's Disease|
- Pharmacokinetic analysis, Safety Assessments including vital signs, physical exam, Symptom Checklist (see below), complete blood count, serum chemistries, urinalysis, and electrocardiogram, Symptom Checklist, ADAScog [ Time Frame: Safety Labs, Physical Exams: 6 times over 7 weeks. Adverse Events assessed 21 times over the course of 7 weeks ] [ Designated as safety issue: Yes ]
- Clinician's Global Impression of Change (ADCS-CGIC), Mini-Mental Status Exam (MMSE), Activities of Daily Living (ADCS-ADL), Neuropsychiatric Inventory, Insulin Sensitivity and Secretion, Biomarkers. APO-E genotyping. [ Time Frame: safety assessed 7 times over 7 weeks, secondary outcomes assessed three times over 7 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||January 2007|
|Study Completion Date:||March 2010|
|Primary Completion Date:||August 2008 (Final data collection date for primary outcome measure)|
Subjects with Alzheimer's Disease
a natural product, found in many foods and plants with mild insulin sensitizing effects
Placebo Comparator: Arm 2
Subjects with Alzheimer's Disease
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
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00470418
|United States, New York|
|VA Medical Center, Bronx|
|Bronx, New York, United States, 10468|
|Principal Investigator:||Hillel Grossman||VA Medical Center, Bronx|