DementiaPhase 2SMArT-HSNCT04120766
Safety and Modulation of ABCC9 Pathways by Nicorandil for the Treatment of Hippocampal Sclerosis of Aging
A Phase 2 study testing Nicorandil in people with Dementia and Mild Cognitive Impairment, run by Gregory Jicha, MD, PhD at 1 site in United States.
Trial summary
Widespread recognition of the current and projected impact of the dementia epidemic has spurred research into novel drug discovery efforts. It is well recognized by most that Alzheimer's disease is not the only form of dementia and that beginning to turn attention to other disease states is critically important in… Read more about this study
- Who is it for?
- Ages 70 years and older
- Conditions the study is for
- Dementia, Mild Cognitive Impairment
- What is being tested?
- Nicorandil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2021to 30 Nov 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 70 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Men or women at least age 75 years
- UPDRS ≤ 7
- Hachinski Ischemic Score ≤ 4
- CSF profile of "A-T-N+" defined as Aβ(1-42)>250pg/ml; Total Tau>50pg/ml; Phospho-tau<30pg/ml within 24 months, Aβ PET scan negative for Alzheimer's disease within 24 months, or plasma profile of Phospho-tau181 negative for Alzheimer's disease ; hippocampal volume ≤ 1 s.d. below age and gender adjusted mean. Plasma ptau181 levels below 3.0 pg/ml.
- English-speaking, to ensure compliance with cognitive testing and study visit procedures
- Involvement of a study partner to supervise medications and compliance with study visits/procedure
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- Stable medical conditions for three months prior to screening visit, with no clinically significant abnormalities of hepatic, renal, and hematologic function defined in the opinion of the investigator
- Stable medications for 4 weeks prior to screening visit
- Ability to ingest oral medications
- Physically acceptable for this study as confirmed by medical history, physical exam, neurological exam and clinical tests.
Who cannot join
- Significant neurologic disease such as Parkinson's disease, stroke, brain tumor, multiple sclerosis or seizure disorder
- Major depression in past 12 months (DSM-IV criteria)
- Recent (in past 12 months) substance abuse
- History of cancer within the past two years, with the exception of non-metastatic prostate or non-melanoma skin cancers such as squamous cell and basal cell carcinomas
- Contra-indications to lumbar puncture (bleeding disorder, platelet count < 100,000, anticoagulant treatment, major abnormality of the spine that would make LP technically difficult) will exclude the participant from engaging in this optional procedure, but the participant may still participate in the main study using plasma p-tau181 and/or amyloid-PET for Alzheimer's disease screening
- Use of any investigational agents within 30 days prior to screening
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- Major surgery within eight weeks prior to the Baseline Visit
- Severe unstable medical illnesses, including uncontrolled cardiac conditions or heart failure (New York Heart Association Class III or IV)
- Blindness, deafness, or any other disability which may prevent the participant from participating or cooperating in the protocol.
- Excluded Medications
- Participants are not eligible for participation in the study if they are taking:
- Experimental drugs
- Vasoactive nitrates such as isosorbide dinitrate
- Drugs for erectile dysfunction such as sildenafil, vardenafil, and tadalafil among others
- Sulfonylurea antidiabetic agents that may confound efficacy measures for the secondary efficacy outcome measures.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Safety and Modulation of ABCC9 Pathways by Nicorandil for the Treatment of Hippocampal Sclerosis of Aging: SMArT-HS
Widespread recognition of the current and projected impact of the dementia epidemic has spurred research into novel drug discovery efforts. It is well recognized by most that Alzheimer's disease is not the only form of dementia and that beginning to turn attention to other disease states is critically important in order to alleviate this burden on the elderly population today This proposal seeks to further progress in this area through the repurposing an existing drug therapy as a potential treatment for Hippocampal Sclerosis of Aging. This disease is seldom recognized clinically and yet is the number one Alzheimer's disease mimic the confounds are diagnostic and treatment of subjects suffering from dementia and as of yet has no potential therapeutic interventions identified. As such, the proposed study represents a cutting-edge, data-driven, low-cost, exploration of a novel disease relevant pathway that may hold promise for global efforts targeting late life dementia which is a major health priority in America today.
Read the detailed description
The proposed project is a pilot clinical trial investigating a potential treatment for hippocampal sclerosis of aging (HS-Aging), a prevalent, high-morbidity mimic of Alzheimer's disease (AD). "AD mimics" (diseases with pathologies other than AD but with similar symptoms) are increasingly appreciated to be important causes of dementia. HS-Aging is a major subtype of dementia, affecting ~10-25% of all persons beyond age 85 and is generally misdiagnosed as AD. The primary aims of this study are to test the safety and efficacy of nicorandil for HS-Aging, based on much prior work elucidating a pharmacologically targetable mechanism for this common cause of cognitive decline and dementia in the aging population. Nicorandil is a vasorelaxant drug, used clinically to treat angina and heart disease disease in the elderly, that has not been tested in humans for the prevention or treatment of dementia. The proposed pilot clinical trial represents the first attempt to expedite drug discovery in HS-Aging, and will guide the rational design of future large-scale Phase II \& III prevention trials for this prevalent disease that is a major contributor to the personal suffering of patients and caregivers as well as a major cost to health care expenditures in America today. The potential success of this trial will not only help millions within immediately available treatment for their condition but may also ameliorate the booming economic burden of healthcare costs in America today related to late life dementia.
- Conditions
- Dementia, Mild Cognitive Impairment
- Being tested
- Nicorandil, Placebo
- Keywords
- TDP-43, Hippocampal sclerosis
- Medical subject headings
- Dementia, Cognitive Dysfunction, Hippocampal Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NicorandilDrug
20 mg po qd
PlaceboDrug
Matching tablet
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Nicorandil 20mg qd Receives: Drug: Nicorandil |
| Placebo | Placebo comparator | Matched placebo qd Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of subjects by arm that experience treatment-related adverse events at week 96
Safety
Measured: 96 weeks
Secondary outcomes (1)
Hippocampal volume (CC)
Change in hippocampal volume over time using freesurfer analyses
Measured: 96 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2019
- Study start1 Dec 2021
- Primary completion1 Sep 2026 (estimated)
- Study completion30 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DementiaStudies 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
- Model description
- Double-blind, placebo controlled, randomized 1:1, single center study of nicorandil (20 mg by mouth daily) or placebo for 96 weeks.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gregory Jicha, MD, PhD
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor-investigator, Gregory Jicha, MD, PhD, University of Kentucky
- Investigators
- Gregory A Jicha, MD, PhD, Principal investigator, University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04120766
- Sponsor's protocol ID
- NIA 1R01AG061111
- Other IDs
- 1R01AG061111
- Acronym
- SMArT-HS
- Status last verified
- Dec 2025
- First submitted
- 6 Oct 2019
- Last updated
- 15 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified data will be shared to other researchers upon request and approval by the study leaders to ensure that data requests do not impinge on the reporting of the primary outcomes or influence study conduct or post conduct analyses. Such IPD will be made available one year following publication of the primary manuscript
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Modulation of ABCC9 Pathways by Nicorandil for the Treatment of Hippocampal Sclerosis of Aging: SMArT-HS
- ClinicalTrials.gov ID
- NCT04120766
- Acronym / sponsor ID
- SMArT-HS / NIA 1R01AG061111
- Conditions
- Dementia, Mild Cognitive Impairment
- Keywords
- TDP-43, Hippocampal sclerosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Gregory Jicha, MD, PhDUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 1 Dec 2021 (actual)
- Primary completion
- 1 Sep 2026 (estimated)
- Study completion
- 30 Nov 2026 (estimated)
- First posted
- 9 Oct 2019 (actual)
- 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.
Widespread recognition of the current and projected impact of the dementia epidemic has spurred research into novel drug discovery efforts. It is well recognized by most that Alzheimer's disease is not the only form of dementia and that beginning to turn attention to other disease states is critically important in order to alleviate this burden on the elderly population today This proposal seeks to further progress in this area through the repurposing an existing drug therapy as a potential treatment for Hippocampal Sclerosis of Aging. This disease is seldom recognized clinically and yet is the number one Alzheimer's disease mimic the confounds are diagnostic and treatment of subjects suffering from dementia and as of yet has no potential therapeutic interventions identified. As such, the proposed study represents a cutting-edge, data-driven, low-cost, exploration of a novel disease relevant pathway that may hold promise for global efforts targeting late life dementia which is a major health priority in America today.
Detailed description
The proposed project is a pilot clinical trial investigating a potential treatment for hippocampal sclerosis of aging (HS-Aging), a prevalent, high-morbidity mimic of Alzheimer's disease (AD). "AD mimics" (diseases with pathologies other than AD but with similar symptoms) are increasingly appreciated to be important causes of dementia. HS-Aging is a major subtype of dementia, affecting ~10-25% of all persons beyond age 85 and is generally misdiagnosed as AD. The primary aims of this study are to test the safety and efficacy of nicorandil for HS-Aging, based on much prior work elucidating a pharmacologically targetable mechanism for this common cause of cognitive decline and dementia in the aging population. Nicorandil is a vasorelaxant drug, used clinically to treat angina and heart disease disease in the elderly, that has not been tested in humans for the prevention or treatment of dementia. The proposed pilot clinical trial represents the first attempt to expedite drug discovery in HS-Aging, and will guide the rational design of future large-scale Phase II \& III prevention trials for this prevalent disease that is a major contributor to the personal suffering of patients and caregivers as well as a major cost to health care expenditures in America today. The potential success of this trial will not only help millions within immediately available treatment for their condition but may also ameliorate the booming economic burden of healthcare costs in America today related to late life dementia.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Double-blind, placebo controlled, randomized 1:1, single center study of nicorandil (20 mg by mouth daily) or placebo for 96 weeks.
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: NicorandilNicorandil 20mg qd |
| Placebo | Placebo comparator | Drug: PlaceboMatched placebo qd |
Who may qualify
- Ages
- 70 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (10 listed)
- Men or women at least age 75 years
- UPDRS ≤ 7
- Hachinski Ischemic Score ≤ 4
- CSF profile of "A-T-N+" defined as Aβ(1-42)>250pg/ml; Total Tau>50pg/ml; Phospho-tau<30pg/ml within 24 months, Aβ PET scan negative for Alzheimer's disease within 24 months, or plasma profile of Phospho-tau181 negative for Alzheimer's disease ; hippocampal volume ≤ 1 s.d. below age and gender adjusted mean. Plasma ptau181 levels below 3.0 pg/ml.
- English-speaking, to ensure compliance with cognitive testing and study visit procedures
Key exclusion criteria (15 listed)
- Significant neurologic disease such as Parkinson's disease, stroke, brain tumor, multiple sclerosis or seizure disorder
- Major depression in past 12 months (DSM-IV criteria)
- Recent (in past 12 months) substance abuse
- History of cancer within the past two years, with the exception of non-metastatic prostate or non-melanoma skin cancers such as squamous cell and basal cell carcinomas
- Contra-indications to lumbar puncture (bleeding disorder, platelet count < 100,000, anticoagulant treatment, major abnormality of the spine that would make LP technically difficult) will exclude the participant from engaging in this optional procedure, but the participant may still participate in the main study using plasma p-tau181 and/or amyloid-PET for Alzheimer's disease screening
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 |
|---|---|---|
| Nicorandil20 mg po qd | Drug | Treatment |
| PlaceboMatching tablet | Drug | Placebo |
Primary outcome
Frequency of subjects by arm that experience treatment-related adverse events at week 96
Time frame: 96 weeks
Safety
1 secondary outcome
Hippocampal volume (CC)
Time frame: 96 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2025.
- Individual participant dataSharing planned: Yes. De-identified data will be shared to other researchers upon request and approval by the study leaders to ensure that data requests do not impinge on the reporting of the primary outcomes or influence study conduct or post conduct analyses. Such IPD will be made available one year following publication of the primary manuscript
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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.
Gregory A Jicha, MD, PhD principal investigator
University of Kentucky
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 Nicorandil in people with Dementia and Mild Cognitive Impairment, run by Gregory Jicha, MD, PhD 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 10 inclusion and 15 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: under way, not looking for participants, as of the sponsor's last update on 15 Dec 2025. 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?
This study is still under way. Results are not available in the source record yet.
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?
Frequency of subjects by arm that experience treatment-related adverse events at week 96 (time frame: 96 weeks). 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 15 Dec 2025.