Modulation of Micro-RNA Pathways by Gemfibrozil in Predementia Alzheimer Disease

The purpose of this study is to assess the safety and efficacy of gemfibrozil in modulating microRNA-107 levels for the prevention of Alzheimer's disease in subjects with intact cognition and mild cognitive impairment

Study Overview

• Status: Completed
• Conditions: Preclinical Alzheimer's Disease
• Intervention / Treatment: Drug: Placebo; Drug: Gemfibrozil

Detailed Description

Double-blind, placebo controlled, parallel-design. 48 cognitively-intact subjects, and 24 subjects with early cognitive decline (CDR 0.5) will be randomly assigned to treatment with gemfibrozil (600 mg orally twice a day) or placebo for 52 weeks. Safety assessments will include routine assessment of adverse events, safety labs, and brain magnetic resonance imaging.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0230
      • University of Kentucky

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 90 years (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Participants must meet all of the following inclusion criteria in order to participate in the study:

1. Men or women aged 65-90, inclusive.
2. Stable medical condition for three months prior to screening visit, with no clinically significant abnormalities of hepatic, renal, and hematologic function defined as follows: Platelets > 100,000, Serum creatinine ≤ 1.6 mg/dL, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 1.5 upper limit of normal, No clinically significant abnormalities of other laboratory studies (CBC, chemistry panel)
3. Non-diabetic or well controlled diabetes confirmed by fasting serum glucose <126 mg/dL.
4. Stable medications for 4 weeks prior to screening visit.

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

   • Exceptions to these criteria may be considered on a case-by-case basis, at the discretion of the Project Director.

Exclusion Criteria:

1. Female participants that are pregnant or of childbearing potential.
2. Unstable medical conditions for three months prior to screening visit such as poorly controlled blood pressure, diabetes, or breathing problems…etc.
3. Clinically significant abnormalities on liver, kidney or other blood tests
4. Significant neurologic disease such as Alzheimer's disease, Parkinson's disease, stroke, brain tumor, multiple sclerosis or seizure disorder.
5. Major depression in past 12 months (DSM-IV criteria), major mental illness such as schizophrenia, or recent (in past 12 months) alcohol or substance abuse.
6. History of invasive cancer within the past two years.
7. Contra-indications to lumbar puncture (bleeding disorder, platelet count < 100,000, anticoagulant treatment, major structural abnormality or sepsis in the area of the lumbosacral spine that would make a lumbar puncture technically difficult).
8. Use of any investigational agents within 30 days prior to screening.
9. Contra-indications to MRI (metallic implants, pacemaker, shrapnel, ect…)
10. Sensitivity, intolerance, or allergies to gemfibrozil or any previous reaction to any cholesterol lowering medicine.
11. Major surgery within eight weeks prior to the Baseline Visit.
12. Blindness, deafness, language difficulties or any other disability which may prevent the potential participant from participating or cooperating in the protocol.

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

    • Exceptions to these criteria may be considered on a case-by-case basis, at the discretion of the examining study physician.

Excluded Medications:

1. Experimental drugs
2. Repaglinide
3. "Statins" including but not limited to atorvastatin (Lipitor), fluvastatin (Lescol), lovastatin (Mevacor), pravastatin (Pravachol), rosuvastatin (Crestor), simvastatin (Zocor), or any combination medicines containing these drugs.
4. Coumadin, warfarin, heparin, lovenox, Xarelto, apixaban or other anticoagulants. (Antiplatelet therapy is acceptable).

NOTE: If these drugs are discontinued 4 weeks or more before screening, then the participant can be eligible for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gemfibrozil; Gemfibrozil 600 mg by mouth twice daily for 48 weeks	Drug: Gemfibrozil
Placebo Comparator: Sugar pill; Matching placebo capsule by mouth twice daily for 48 weeks	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety	Adverse events reported during the course of the trial	52 weeks
microRNA-107 levels	MicroRNA-107 levels will be measured in serum and cerebrospinal fluid	48 weeks
beta-amyloid levels	Beta-amyloid 1-40 and 1-42 levels will be measured in cerebrospinal fluid at baseline and at 48 weeks	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Free and cued selective reminding test (FCSRT)	The FCSRT is a sensitive measure of memory performance that will be measured at baseline and after 48 weeks of gemfibrozil treatment	48 weeks
Paired associates learning (PAL)	The PAL is a sensitive, computerized measure of memory performance that will be measured at baseline and after 48 weeks of gemfibrozil treatment	48 weeks

Collaborators and Investigators

• Sponsor: Gregory Jicha, 323-5550
• Investigators: Principal Investigator: Gregory A Jicha, MD, PhD, University of Kentucky

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2014
• Primary Completion (Actual): June 30, 2018
• Study Completion (Actual): June 1, 2019

Study Registration Dates

• First Submitted: January 22, 2014
• First Submitted That Met QC Criteria: January 23, 2014
• First Posted (Estimate): January 24, 2014

Study Record Updates

• Last Update Posted (Actual): October 8, 2019
• Last Update Submitted That Met QC Criteria: October 6, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: mild cognitive impairment; Alzheimer disease; normal cognition
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP2C8 Inhibitors; Gemfibrozil
• Other Study ID Numbers: R01AG042419 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No