A Single Site, Randomized, Double-blind, Placebo Controlled Trial of NIC5-15 in Subjects With Alzheimer's Disease

Humanetics

Status and phase

Completed

Phase 2

Conditions

Alzheimer's Disease

Dementia

Treatments

Drug: Placebo

Drug: Drug: NIC5-15

Study type

Interventional

Funder types

Industry

Other U.S. Federal agency

NIH

Identifiers

NCT01928420

MHBB-009-06S

NCT01928420

R21AT003302-01A1 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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

Full 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.

Enrollment

30 patients

Sex

All

Ages

40 to 95 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

NINCDS/ADRDA criteria for probable AD
MMSE between 12-27
Treatment with a cholinesterase inhibitor or an NMDA (N-methyl-D-asparate) antagonist with stable dose for at least 12 weeks
Home monitoring available for supervision of medications
Caregiver available to accompany patient to all visits and willing to participate in study as informant
Fluent in English or Spanish
Medical stability for this study as confirmed by review of records, internist's physical exam, neurological exam, and laboratory tests
Stable doses of non-excluded medication
No evidence of hepatic insufficiency
Able to swallow oral medications
Ability to participate in the informed consent process

Exclusion criteria

History of Diabetes Mellitus (OGTT criteria) requiring treatment with an excluded antidiabetic medication (see below) or history of hypoglycemia
Active hepatic or renal disease
Cardiac disease including history of congestive heart failure or current treatment for CHF; history of recent myocardial infarction
Use of another investigational drug within the past two months
History of clinically significant stroke
History of seizure or head trauma with disturbance of consciousness within the past two years
Major mental illness including psychotic disorders, bipolar disorder, or major depressive episode within the past two years Medication Exclusion
Current use of oral hypoglycemic agents including sulfonylureas and meglintinides
Current or past treatment with insulin for longer than two weeks
Current use of drugs with significant anticholinergic or antihistaminic properties