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

• Status: Not yet recruiting
• Trial end date: 2024-11-20
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Gregory Jicha, MD, PhD; University of Kentucky
• Treatments: Nicorandil

Criteria

Inclusion Criteria:

1. Men or women at least age 75 years

2. UPDRS ≤ 7

3. Hachinski Ischemic Score ≤ 4

4. CSF profile of "A-T-N+" defined as Aβ(1-42)>250pg/ml; Total Tau>50pg/ml; Phospho-tau<30pg/ml; hippocampal volume ≤ 1 s.d. below age and gender adjusted mean

5. English-speaking, to ensure compliance with cognitive testing and study visit procedures

6. Involvement of a study partner to supervise medications and compliance with study visits/procedure

7. 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

8. Stable medications for 4 weeks prior to screening visit

9. Ability to ingest oral medications

10. Physically acceptable for this study as confirmed by medical history, physical exam, neurological exam and clinical tests.

Exclusion Criteria:

1. Significant neurologic disease such as Parkinson's disease, stroke, brain tumor, multiple sclerosis or seizure disorder

2. Major depression in past 12 months (DSM-IV criteria)

3. Recent (in past 12 months) substance abuse

4. 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

5. Contra-indications to lumbar puncture (bleeding disorder, platelet count < 100,000, anticoagulant treatment, major abnormality of the spine that would make LP technically difficult)

6. Use of any investigational agents within 30 days prior to screening

7. Major surgery within eight weeks prior to the Baseline Visit

8. Severe unstable medical illnesses, including uncontrolled cardiac conditions or heart failure (New York Heart Association Class III or IV)

9. 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:

1. Experimental drugs

2. Vasoactive nitrates such as isosorbide dinitrate

3. Drugs for erectile dysfunction such as sildenafil, vardenafil, and tadalafil among others

4. Sulfonylurea antidiabetic agents that may confound efficacy measures for the secondary efficacy outcome measures.