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

• ClinicalTrials.gov Identifier: NCT02045056
• Recruitment Status: Completed
• First Posted: January 24, 2014
• Last Update Posted: October 8, 2019
• Sponsor: Gregory Jicha, 323-5550
• Information provided by (Responsible Party): Gregory Jicha, 323-5550, University of Kentucky

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Preclinical Alzheimer's Disease	Drug: Gemfibrozil; Drug: Placebo	Early Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 72 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: Modulation of Micro-RNA Pathways by Gemfibrozil in Predementia Alzheimer Disease
• Actual Study Start Date: May 2014
• Actual Primary Completion Date: June 30, 2018
• Actual Study Completion Date: June 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Safety [ Time Frame: 52 weeks ]
   Adverse events reported during the course of the trial
2. microRNA-107 levels [ Time Frame: 48 weeks ]
   MicroRNA-107 levels will be measured in serum and cerebrospinal fluid
3. beta-amyloid levels [ Time Frame: 48 weeks ]
   Beta-amyloid 1-40 and 1-42 levels will be measured in cerebrospinal fluid at baseline and at 48 weeks

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 65 Years to 90 Years (Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

United States, Kentucky

University of Kentucky

Lexington, Kentucky, United States, 40536-0230

Sponsors and Collaborators

Gregory Jicha, 323-5550

Investigators

• Principal Investigator: Gregory A Jicha, MD, PhD; University of Kentucky

More Information

• Responsible Party: Gregory Jicha, 323-5550, Sponsor/PI, University of Kentucky
• ClinicalTrials.gov Identifier: NCT02045056
• Other Study ID Numbers: R01AG042419 ( U.S. NIH Grant/Contract )
• First Posted: January 24, 2014
• Last Update Posted: October 8, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Gregory Jicha, 323-5550, University of Kentucky:

Alzheimer disease; mild cognitive impairment; normal cognition

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Gemfibrozil; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Cytochrome P-450 CYP2C8 Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors