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

Must not be taking: Experimental drugs, Vasoactive nitrates, ED drugs, Sulfonylureas

Disqualifiers: Parkinson's, Stroke, Major depression, Cancer, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 96 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Nicorandil, an existing drug, can help treat Hippocampal Sclerosis, a condition that mimics Alzheimer's and affects memory and thinking. The researchers aim to provide new insights into treating this lesser-known form of dementia, which currently lacks treatment options. Participants will receive either Nicorandil or a placebo to compare the effects. Suitable candidates are individuals aged 75 or older who do not have major neurological issues and have stable health conditions. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that Nicorandil is likely to be safe for humans?

Research has shown that nicorandil has been studied for safety in humans. In a year-long study with 199 patients suffering from severe chronic stable angina, nicorandil proved safe for the heart, suggesting it may be well-tolerated.

Although this study focused on a different condition, the positive safety results support its potential use in other areas. However, since the current trial for hippocampal sclerosis is in an early stage, further research is necessary to confirm its safety for this specific use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Hippocampal Sclerosis?

Unlike the standard treatments for hippocampal sclerosis, which often include anti-seizure medications, Nicorandil brings a fresh approach with its unique mechanism as a potassium channel opener and nitrate donor. This dual action could potentially improve blood flow and protect brain cells, offering a novel way to tackle the condition. Researchers are excited because this could mean better symptom management and possibly fewer side effects compared to current options.

What evidence suggests that Nicorandil might be an effective treatment for Hippocampal Sclerosis?

Research suggests that nicorandil might help treat conditions like hippocampal sclerosis, a type of dementia. Studies have shown that nicorandil can help mice with memory problems live longer and learn better. It also reduces inflammation, often linked to brain issues. In another study, nicorandil reduced depression-like behaviors in rats, indicating it might improve brain function. Although direct evidence for its effects on hippocampal sclerosis is limited, these findings suggest that nicorandil could benefit brain health. Participants in this trial will receive either nicorandil or a matched placebo to evaluate its potential benefits for hippocampal sclerosis. ^{1 2 4 6 7}

Who Is on the Research Team?

Gregory A Jicha, MD, PhD

Principal Investigator

University of Kentucky

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04120766

Study Details | NCT04120766 | Safety and Modulation of ... 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 ...

2. reporter.nih.gov reporter.nih.gov/project-details/10314015

Safety and modulation of ABCC9 pathways by nicorandil ... Evaluating the safety of nicorandil administration in the elderly at risk for HS-aging (this is the primary outcome measure) that will inform future trial ...

3. withpower.com withpower.com/trial/phase-3-sclerosis-10-2020-7a8bc

Nicorandil for Hippocampal Sclerosis (SMArT-HS Trial) By using a progressive titration scheme, the incidence of headaches was significantly reduced to 2.7%, and 70% of patients continued treatment with nicorandil ...

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/bpa.13312

Nicorandil treatment improves survival and spatial learning ... Progranulin knockout mice display a profound reduction in survival, as well as increased inflammation and cognitive impairment.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11686086/

Nicorandil Ameliorates Depression‐Like Behaviors After ... In this study, we identified that nicorandil administration significantly attenuates depression‐like behavior in rats with TBI. Mechanistically, ...

6. trialx.com trialx.com/clinical-trials/listings/231512/safety-and-modulation-of-abcc9-pathways-by-nicorandil-for-the-treatment-of-hippocampal-sclerosis-of-aging/

Safety and Modulation of ABCC9 Pathways by Nicorandil ... 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 ...

7. scholars.uky.edu scholars.uky.edu/en/projects/safety-and-modulation-of-abcc9-pathways-by-nicorandil-for-the-tre-4/

Safety and Modulation of ABCC9 Pathways by Nicorandil for ... Hippocampal Sclerosis · 100% ; Nicorandil · 100% ; Alzheimer's Disease · 80% ; Diseases · 40% ; Placebo · 40%.