Nicorandil for Hippocampal Sclerosis

(SMArT-HS Trial)

Overseen By Gregory A Jicha, MD, PhD

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: Gregory Jicha, MD, PhD

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 96 weeks

64 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing nicorandil, a heart medication, to see if it can help elderly patients with Hippocampal Sclerosis of Aging (HS-Aging), a condition often mistaken for Alzheimer's disease. HS-Aging affects many older adults and currently has no specific treatments. Nicorandil may help by improving blood flow, potentially reducing symptoms of dementia. Nicorandil has shown potential as a therapeutic agent for Alzheimer's disease by inhibiting oxidative stress and amyloid-β precursor protein processing.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, including experimental drugs, vasoactive nitrates, drugs for erectile dysfunction, and sulfonylurea antidiabetic agents. If you are on any of these, you would need to stop them to participate.

What data supports the effectiveness of the drug Nicorandil for treating hippocampal sclerosis?

Research on nicotinic receptors, which are involved in memory and cognitive function, suggests that stimulating these receptors can improve learning and memory in conditions like Alzheimer's disease. Nicorandil may have similar effects due to its potential action on these receptors, although direct evidence for hippocampal sclerosis is not available. ^{1 2 3 4 5}

Is nicorandil generally safe for human use?

Nicorandil has been studied for long-term safety in treating coronary heart disease, with common side effects like mild to moderate headaches, dizziness, and gastrointestinal issues, which often resolve after a few days. It has shown a satisfactory cardiovascular safety profile and does not significantly alter laboratory parameters. ^{6 7 8 9 10}

How does the drug Nicorandil differ from other treatments for hippocampal sclerosis?

Nicorandil is unique because it may target nicotinic receptors in the brain, which are involved in memory and cognitive function. This mechanism is different from other treatments that may not focus on these receptors, potentially offering a novel approach to managing hippocampal sclerosis. ^{1 3 4 5 11}

Research Team

Gregory A Jicha, MD, PhD

Principal Investigator

University of Kentucky

Eligibility Criteria

This trial is for English-speaking men and women aged 75 or older with cognitive impairment but not Alzheimer's. They must have a stable medical condition, no recent severe illnesses, cancer history (with exceptions), or major surgeries. Participants need a study partner to help with medication and visits, be able to take oral meds, and have specific CSF profiles or brain scans.

Inclusion Criteria

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

My health is good enough for this study, as confirmed by various medical exams.

Exclusion Criteria

I am not taking experimental drugs, vasoactive nitrates, erectile dysfunction medication, or sulfonylurea antidiabetic agents.

I have not had major surgery in the last 8 weeks.

I haven't had cancer in the last 2 years, except for non-spreading prostate or skin cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Nicorandil 20mg or placebo daily to test safety and efficacy for HS-Aging

96 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Nicorandil

Trial Overview The trial tests Nicorandil against a placebo in treating Hippocampal Sclerosis of Aging—a dementia mimic without current treatments. It explores repurposing an existing drug to modulate ABCC9 pathways as a novel approach to alleviate late-life dementia symptoms.

Participant Groups

Group I: Treatment Experimental Treatment 1 Intervention

Nicorandil 20mg qd

Group II: Placebo Placebo Group 1 Intervention

Matched placebo qd

Who Is Running the Clinical Trial?

Gregory Jicha, MD, PhD

Lead Sponsor

Trials

1

Recruited

60+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Findings from Research

In a 1-year study involving 199 patients with severe chronic stable angina, nicorandil was found to have a satisfactory cardiovascular safety profile, with the most common side effect being mild to moderate headaches, which led to a withdrawal rate of 9.6%.

By using a progressive titration scheme, the incidence of headaches was significantly reduced to 2.7%, and 70% of patients continued treatment with nicorandil by the end of the study, indicating its long-term tolerability and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicorandil safety in the long-term treatment of coronary heart disease. Witchitz, S., Darmon, JY.[2019]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Ventral hippocampal alpha7 and alpha4beta2 nicotinic receptor blockade and clozapine effects on memory in female rats. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Human nicotinic receptors--their role in aging and dementia. [2022]

3. China pubmed.ncbi.nlm.nih.gov

[Role of central neuronal nicotinic receptor in the inhibitory effect of isoflurane on synaptic long-term potentiation in hippocampal slices of rats]. [2014]

4. United States pubmed.ncbi.nlm.nih.gov

Nicotinic receptors and neurodegenerative dementing diseases: basic research and clinical implications. [2022]

5. Czech Republic pubmed.ncbi.nlm.nih.gov

Changes in the number of nitrergic neurons in rats hippocampus following nicotine administration. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

The KATP channel opener, nicorandil, ameliorates brain damage by modulating synaptogenesis after ischemic stroke. [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Effect of nicorandil on the spatial arrangement of primary motor cortical neurons in the sub-acute phase of stroke in a rat model. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Nicorandil inhibits oxidative stress and amyloid-β precursor protein processing in SH-SY5Y cells overexpressing APPsw. [2020]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of nicorandil in neuroprotective activation of PI3K/AKT pathways in a cellular model of Alzheimer's disease. [2013]

10. United States pubmed.ncbi.nlm.nih.gov

Nicorandil safety in the long-term treatment of coronary heart disease. [2019]

11. Germany pubmed.ncbi.nlm.nih.gov

Acute effects of the selective cholinergic channel activator (nicotinic agonist) ABT-418 in Alzheimer's disease. [2022]