Clinical trial NCT01928420: A Single Site, Randomized, Double-blind, Placebo Controlled Trial of NIC5-15 in Subjects With Alzheimer's Disease
Official title: A Single Site, Randomized, Double-blind, Placebo Controlled Trial of NIC5-15 in Subjects With Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alzheimer's Disease
Dementia
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
Lead sponsor: Humanetics Corporation
Sponsor class: INDUSTRY
Collaborators: name: National Center for Complementary and Integrative Health (NCCIH)
name: James J. Peters Veterans Affairs Medical Center
First posted: 2013-08-26
Enrollment: 30
Sex: ALL
Minimum age (years): 40
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog)Score
timeFrame: Over 6 months, measured at visits 2 (week 2), 6 (week 12), 8 (week 24)
Secondary outcomes:
measure: Change in Alzheimer's Disease Cooperative Study Clinician's Global Impression of Change (ADCS-CCGIC) Score
timeFrame: Over 6 months, measured at visits 2 (week 2), 6 (week 12), 8 (week 24)
measure: Change in Mini-Mental State Examination (MMSE) Score
timeFrame: Over 6 months, measured at visits 2 (week 2), 6 (week 12), 8 (week 24)
measure: Change in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) Score
timeFrame: Over 6 months, measured at visits 2 (week 2), 6 (week 12), 8 (week 24)
measure: Change in Neuropsychiatric Inventory (NPI) Score
timeFrame: Over 6 months, measured at visits 2 (week 2), 6 (week 12), 8 (week 24)
measure: Changes in AD Biomarkers
timeFrame: Blood collected at visits 2 (week 2), 6 (week 12), 8 (week 24)
measure: APO-E genotyping
timeFrame: Collected at visit 2 (week 2)
Other outcomes:
measure: Symptoms Checklist and Adverse Event Assessment
timeFrame: 6 Months, conducted at visits 3 (week 2), 4 (week 4), 5 (week 8), 6 (week 12), 7 (week 18), 8 (week 24)
measure: Safety Laboratory Assessments
timeFrame: 6 Months, conducted at visits 1 (week 1), 3 (week 2), 4 (week 4), 5 (week 8), 6 (week 12), 7 (week 18), 8 (week 24)
measure: Neurological examination
timeFrame: 6 Months, conducted at visits 1 (week 1), 6 (week 12), 8 (week 24)
measure: Physical examination
timeFrame: 6 Months, conducted at visits 1 (week 1), 3 (week 2), 5 (week 8), 6 (week 12), 7 (week 18), 8 (week 24)
measure: Pharmacokinetic analysis
timeFrame: 6 Months, conducted at visits 2 (week 2), 8 (week 24)
Locations:
city: Bronx
country: United States
facility: James J Peters Veterans Affairs Medical Center
state: New York
Study officials:
affiliation: James J. Peters Veterans Affairs Medical Center
name: Hillel Grossman, MD
role: PRINCIPAL_INVESTIGATOR
References: