Alzheimer's DiseasePhase 2NCT01928420
A Single Site, Randomized, Double-blind, Placebo Controlled Trial of NIC5-15 in Subjects With Alzheimer's Disease
A Phase 2 study testing Drug: NIC5-15 in people with Alzheimer's Disease and Dementia, run by Humanetics Corporation at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the safety and efficacy of NIC5-15 in the treatment of Alzheimer's Disease. Read more about this study
- Who is it for?
- Ages 40 to 95 years
- Conditions the study is for
- Alzheimer's Disease, Dementia
- What is being tested?
- Drug: NIC5-15
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2007to Jun 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 95 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
James J Peters Veterans Affairs Medical Center
The Bronx, New York, 10468
About this study
The purpose of this study is to evaluate the safety and efficacy of NIC5-15 in the treatment of Alzheimer's Disease.
Read the 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:
- 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.
- 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.
- Conditions
- Alzheimer's Disease, Dementia
- Being tested
- Drug: NIC5-15, Placebo
- 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
- Medical subject headings
- Alzheimer Disease, Dementia, Diabetes Mellitus, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Neurodegenerative Diseases, Delirium
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Drug: NIC5-15Drug
Also called Pinitol
A natural product, found in many foods and plants with mild insulin sensitizing effects
PlaceboDrug
Subjects with Alzheimer's Disease placebo comparator
| Study group | Role | What they receive |
|---|---|---|
| NIC5-15 | Experimental | Subjects with Alzheimer's Disease Intervention: Drug: NIC5-15 Receives: Drug: Drug: NIC5-15 |
| Placebo | Placebo comparator | Subjects with Alzheimer's Disease Intervention: Drug: Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog)Score
A psychometric instrument that evaluates memory, attention, reasoning, language, orientation, and praxis.
Measured: Over 6 months, measured at visits 2 (week 2), 6 (week 12), 8 (week 24)
Secondary outcomes (6)
Change in Alzheimer's Disease Cooperative Study Clinician's Global Impression of Change (ADCS-CCGIC) Score
A systematic method for assessing clinically significant change in a clinical trial as viewed by an independent skilled and experienced clinician . The ADCS-CGIC focuses on clinician's observations of change in the subject's cognitive, functional, and behavioral performance since the beginning of a trial. It relies on both direct examination of the subject and an interview of an informant. Unlike a targeted symptom scale, it takes into account a subject's overall function in the cognitive, behavioral, and functional activity domains.
Measured: Over 6 months, measured at visits 2 (week 2), 6 (week 12), 8 (week 24)
Change in Mini-Mental State Examination (MMSE) Score
A frequently used screening instrument for Alzheimer's disease drug studies. It evaluates orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two intersecting polygons
Measured: Over 6 months, measured at visits 2 (week 2), 6 (week 12), 8 (week 24)
Change in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) Score
ADCS-ADL assesses functional performance in subjects with Alzheimer's disease. In a structured interview format, informants are queried as to whether subjects attempted each item in the inventory during the prior 4 weeks and their level of performance. The ADCS-ADL scale discriminates well between normal controls and mild AD patients. It has good test-retest reliability. The ADCS-ADL includes some items from traditional basic ADL scales (e.g., grooming, dressing, walking, bathing, feeding, toileting) as well as items from instrumental activities of daily living scales (e.g., shopping, preparing meals, using household appliances, keeping appointments, reading).
Measured: Over 6 months, measured at visits 2 (week 2), 6 (week 12), 8 (week 24)
Change in Neuropsychiatric Inventory (NPI) Score
The NPI is a well-validated, reliable, multi-item instrument to assess psychopathology and behavior in AD based on interview with the informant.
Measured: Over 6 months, measured at visits 2 (week 2), 6 (week 12), 8 (week 24)
Changes in AD Biomarkers
Plasma beta-amyloid proteins will be collected from blood samples obtained at visit 2 (week 2), visit 6 (week 12), and visit 8 (week 24).
Measured: Blood collected at visits 2 (week 2), 6 (week 12), 8 (week 24)
APO-E genotyping
APOe e4 is an important genetic risk factor for AD. In this trial, as in many studies of AD and memory and cognition in aging, the APOe e4 allele will be analyzed as a predictor of clinical change over time.
Measured: Collected at visit 2 (week 2)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2013 (estimated)
- Study startApr 2007
- Primary completionJun 2014
- Study completionJun 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Humanetics Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Center for Complementary and Integrative Health (NCCIH), James J. Peters Veterans Affairs Medical Center
- Responsible party
- Sponsor
- Investigators
- Hillel Grossman, MD, Principal investigator, James J. Peters Veterans Affairs Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01928420
- Sponsor's protocol ID
- NCT01928420
- Other IDs
- R21AT003302-01A1, MHBB-009-06S
- Status last verified
- Oct 2016
- First submitted
- 17 Aug 2012
- Last updated
- 17 Oct 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Site, Randomized, Double-blind, Placebo Controlled Trial of NIC5-15 in Subjects With Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT01928420
- Acronym / sponsor ID
- NCT01928420
- Conditions
- Alzheimer's Disease, Dementia
- Keywords
- Alzheimer Disease, Alzheimer Type Senile Dementia, Alzheimer's Disease, clinical trial, dementia, diabetes, dietary supplements, Senile Dementia, Alzheimer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Humanetics CorporationIndustry (pharma, biotech, devices)
- Collaborators
- National Center for Complementary and Integrative Health (NCCIH), James J. Peters Veterans Affairs Medical Center
- Study start
- Apr 2007
- Primary completion
- Jun 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 26 Aug 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NIC5-15 | Experimental | Drug: Drug: NIC5-15Subjects with Alzheimer's Disease Intervention: Drug: NIC5-15 |
| Placebo | Placebo comparator | Drug: PlaceboSubjects with Alzheimer's Disease Intervention: Drug: Placebo |
Who may qualify
- Ages
- 40 to 95 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Drug: NIC5-15Also: PinitolA natural product, found in many foods and plants with mild insulin sensitizing effects | Drug | NIC5-15 |
| PlaceboSubjects with Alzheimer's Disease placebo comparator | Drug | Placebo |
Primary outcome
Change in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog)Score
Time frame: Over 6 months, measured at visits 2 (week 2), 6 (week 12), 8 (week 24)
A psychometric instrument that evaluates memory, attention, reasoning, language, orientation, and praxis.
6 secondary outcomes
Change in Alzheimer's Disease Cooperative Study Clinician's Global Impression of Change (ADCS-CCGIC) Score
Time frame: Over 6 months, measured at visits 2 (week 2), 6 (week 12), 8 (week 24)
Change in Mini-Mental State Examination (MMSE) Score
Time frame: Over 6 months, measured at visits 2 (week 2), 6 (week 12), 8 (week 24)
Change in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) Score
Time frame: Over 6 months, measured at visits 2 (week 2), 6 (week 12), 8 (week 24)
Change in Neuropsychiatric Inventory (NPI) Score
Time frame: Over 6 months, measured at visits 2 (week 2), 6 (week 12), 8 (week 24)
Changes in AD Biomarkers
Time frame: Blood collected at visits 2 (week 2), 6 (week 12), 8 (week 24)
APO-E genotyping
Time frame: Collected at visit 2 (week 2)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2016.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hillel Grossman, MD principal investigator
James J. Peters Veterans Affairs Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Drug: NIC5-15 in people with Alzheimer's Disease and Dementia, run by Humanetics Corporation at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog)Score (time frame: Over 6 months, measured at visits 2 (week 2), 6 (week 12), 8 (week 24)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Oct 2016.