What is the mechanism of action of this treatment?

The most common treatments for Mild Cognitive Impairment (MCI) include cholinesterase inhibitors and memantine. Cholinesterase inhibitors, such as donepezil, galantamine, and rivastigmine, increase acetylcholine levels in the brain by inhibiting its breakdown, thereby enhancing communication between nerve cells involved in memory and learning. Memantine regulates glutamate activity, preventing excessive stimulation that can lead to neuronal damage. These treatments are important for MCI patients as they aim to improve cognitive function and potentially slow the progression of cognitive decline. Ongoing research into repurposed drug therapies targeting novel pathways may offer additional options for managing MCI.

What side effects are associated with this type of intervention?

The most common treatments for Mild Cognitive Impairment (MCI) include cholinesterase inhibitors and memantine. Cholinesterase inhibitors, such as donepezil, rivastigmine, and galantamine, often cause gastrointestinal side effects like nausea, vomiting, and diarrhea, as well as muscle cramps, fatigue, and insomnia. Memantine, an NMDA receptor antagonist, is generally well-tolerated but can lead to dizziness, headache, confusion, and occasionally hallucinations and agitation. These side effects should be considered when determining the best treatment approach for patients with MCI.

What prior FDA approvals exist?

FDA-approved treatments for Mild Cognitive Impairment (MCI) primarily include cholinesterase inhibitors like donepezil, rivastigmine, and galantamine, which are also used in Alzheimer's disease to improve cognitive function. Memantine, an NMDA receptor antagonist, is another drug approved for moderate to severe Alzheimer's disease and has been studied for its potential benefits in MCI. These treatments aim to enhance cholinergic transmission and modulate glutamatergic activity, respectively. While these drugs provide symptomatic relief, their efficacy in altering the disease trajectory remains limited, and ongoing research continues to explore their potential in novel therapeutic pathways.

What other types of research exist?

Promising novel alternatives for treating Mild Cognitive Impairment (MCI) in 2024 include: 1) Anti-amyloid therapies such as monoclonal antibodies targeting amyloid-beta plaques, 2) Neuroprotective agents like BDNF (Brain-Derived Neurotrophic Factor) enhancers, 3) Lifestyle interventions including structured physical exercise and cognitive training programs, 4) Digital therapeutics such as app-based cognitive behavioral therapy (CBT) for cognitive enhancement, and 5) Personalized medicine approaches using genetic and biomarker profiling to tailor treatments.

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Potassium Channel Opener

Nicorandil for Hippocampal Sclerosis (SMArT-HS Trial)

Phase 2

Waitlist Available

Led By Gregory A Jicha, MD, PhD

Research Sponsored by Gregory Jicha, MD, PhD

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

UPDRS ≤ 7

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

Must not have

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.

Major surgery within eight weeks prior to the Baseline Visit

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 96 weeks

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

While the side effects are not explicitly listed here, common ones for Nicorandil may include headaches, dizziness, nausea or weakness. As it's used for heart-related conditions too, participants on certain heart medications are excluded due to potential adverse interactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My Parkinson's symptoms are mild.

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My tests show I might not have Alzheimer's based on specific protein levels and brain scans.

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I am 75 years old or older.

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I can take pills by mouth.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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

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I have been diagnosed with major depression in the last year.

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I have a serious neurological condition like Parkinson's, stroke, brain tumor, MS, or seizures.

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I do not have any disabilities that would stop me from following the study's requirements.

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I do not have severe heart problems or uncontrolled illnesses.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 96 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~96 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 96 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Frequency of subjects by arm that experience treatment-related adverse events at week 96

Secondary study objectives

Hippocampal volume (CC)

Side effects data

From 2014 Phase 4 trial • 402 Patients • NCT01396395

Headache

Nausea

Glaucoma

Chest pain

Gastric ulcer

Peripheral edema

Dizziness

Coronary artery disease

Angina

Diabetic foot

Multiple myeloma

Sudden death

Unstable angina

Supraventricular tachycardia

Duodenal ulcer

Chronic renal failure

Increased blood pressure

100%

80%

60%

40%

20%

Study treatment Arm

Standard Treatment Plus Nicorandil

Standard Treatment

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: TreatmentExperimental Treatment1 Intervention

Nicorandil 20mg qd

Group II: PlaceboPlacebo Group1 Intervention

Matched placebo qd

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Nicorandil

2018

Completed Phase 4

~840

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Mild Cognitive Impairment (MCI) include cholinesterase inhibitors and memantine. Cholinesterase inhibitors, such as donepezil, galantamine, and rivastigmine, increase acetylcholine levels in the brain by inhibiting its breakdown, thereby enhancing communication between nerve cells involved in memory and learning. Memantine regulates glutamate activity, preventing excessive stimulation that can lead to neuronal damage. These treatments are important for MCI patients as they aim to improve cognitive function and potentially slow the progression of cognitive decline. Ongoing research into repurposed drug therapies targeting novel pathways may offer additional options for managing MCI.

Effect of galantamine on verbal repetition in AD: a secondary analysis of the VISTA trial.