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Safety and Modulation of ABCC9 Pathways by Nicorandil for the Treatment of Hippocampal Sclerosis of Aging (SMArT-HS)

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ClinicalTrials.gov Identifier: NCT04120766
Recruitment Status : Recruiting
First Posted : October 9, 2019
Last Update Posted : November 24, 2021
Sponsor:
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Gregory Jicha, MD, PhD, University of Kentucky

Tracking Information
First Submitted Date  ICMJE October 6, 2019
First Posted Date  ICMJE October 9, 2019
Last Update Posted Date November 24, 2021
Estimated Study Start Date  ICMJE November 2021
Estimated Primary Completion Date November 1, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 7, 2019)
Frequency of subjects by arm that experience treatment-related adverse events at week 96 [ Time Frame: 96 weeks ]
Safety
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 7, 2019)
Hippocampal volume (CC) [ Time Frame: 96 weeks ]
Change in hippocampal volume over time using freesurfer analyses
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Modulation of ABCC9 Pathways by Nicorandil for the Treatment of Hippocampal Sclerosis of Aging
Official Title  ICMJE Safety and Modulation of ABCC9 Pathways by Nicorandil for the Treatment of Hippocampal Sclerosis of Aging: SMArT-HS
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.
Detailed Description The proposed project is a pilot clinical trial investigating a potential treatment for hippocampal sclerosis of aging (HS-Aging), a prevalent, high-morbidity mimic of Alzheimer's disease (AD). "AD mimics" (diseases with pathologies other than AD but with similar symptoms) are increasingly appreciated to be important causes of dementia. HS-Aging is a major subtype of dementia, affecting ~10-25% of all persons beyond age 85 and is generally misdiagnosed as AD. 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 targetable mechanism for this common cause of cognitive decline and dementia in the aging population. Nicorandil is a vasorelaxant drug, used clinically to treat angina and heart disease disease in the elderly, that has not been tested in humans for the prevention or treatment of dementia. The proposed pilot clinical trial represents the first attempt to expedite drug discovery in HS-Aging, and will guide the rational design of future large-scale Phase II & III prevention trials for this prevalent disease that is a major contributor to the personal suffering of patients and caregivers as well as a major cost to health care expenditures in America today. The potential success of this trial will not only help millions within immediately available treatment for their condition but may also ameliorate the booming economic burden of healthcare costs in America today related to late life dementia.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Double-blind, placebo controlled, randomized 1:1, single center study of nicorandil (20 mg by mouth daily) or placebo for 96 weeks.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Double-blind, placebo controlled, randomized 1:1, single center study of nicorandil (20 mg by mouth daily) or placebo for 96 weeks.
Primary Purpose: Treatment
Condition  ICMJE
  • Dementia
  • Mild Cognitive Impairment
Intervention  ICMJE
  • Drug: Nicorandil
    20 mg po qd
  • Drug: Placebo
    Matching tablet
Study Arms  ICMJE
  • Experimental: Treatment
    Nicorandil 20mg qd
    Intervention: Drug: Nicorandil
  • Placebo Comparator: Placebo
    Matched placebo qd
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 7, 2019)
64
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 20, 2024
Estimated Primary Completion Date November 1, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 75 Years and older   (Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Gregory A Jicha, MD, PhD 18593235550 gregory.jicha@uky.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04120766
Other Study ID Numbers  ICMJE NIA 1R01AG061111
1R01AG061111 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: De-identified data will be shared to other researchers upon request and approval by the study leaders to ensure that data requests do not impinge on the reporting of the primary outcomes or influence study conduct or post conduct analyses. Such IPD will be made available one year following publication of the primary manuscript
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: one year following publishing the primary study results
Responsible Party Gregory Jicha, MD, PhD, University of Kentucky
Study Sponsor  ICMJE Gregory Jicha, MD, PhD
Collaborators  ICMJE National Institute on Aging (NIA)
Investigators  ICMJE
Principal Investigator: Gregory A Jicha, MD, PhD University of Kentucky
PRS Account University of Kentucky
Verification Date November 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP