Safety and Modulation of ABCC9 Pathways by Nicorandil for the Treatment of Hippocampal Sclerosis of Aging

NCT04120766 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: NIA 1R01AG0611111R01AG061111
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Dementia; Mild Cognitive Impairment

Keywords

TDP-43; Hippocampal sclerosis

Outcome Measures

Primary Outcomes (1)

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

  Safety

  96 weeks

Secondary Outcomes (1)

• Hippocampal volume (CC)

  96 weeks

Study Arms (2)

Treatment

EXPERIMENTAL

Nicorandil 20mg qd

Drug: Nicorandil

Placebo

PLACEBO COMPARATOR

Matched placebo qd

Drug: Placebo

Interventions

Nicorandil DRUG

20 mg po qd

Treatment

Placebo DRUG

Matching tablet

Placebo

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Gregory Jicha, MD, PhD: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

University of Kentucky

Lexington, Kentucky, 40504, United States

Location

MeSH Terms

Conditions

Dementia; Cognitive Dysfunction; Hippocampal Sclerosis

Interventions

Nicorandil

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Nitrates; Organic Chemicals; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Gregory A Jicha, MD, PhD

  University of Kentucky

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind, placebo controlled, randomized 1:1, single center study of nicorandil (20 mg by mouth daily) or placebo for 96 weeks.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD-PhD Professor of Neurology

Model Details: Double-blind, placebo controlled, randomized 1:1, single center study of nicorandil (20 mg by mouth daily) or placebo for 96 weeks.

Study Record Dates

• First Submitted: October 6, 2019
• First Posted: October 9, 2019
• Study Start: December 1, 2021
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): November 30, 2026
• Last Updated: December 15, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: one year following publishing the primary study results

Locations

US (1)