Clinical trial NCT02045056: Modulation of Micro-RNA Pathways by Gemfibrozil in Predementia Alzheimer Disease
Official title: Modulation of Micro-RNA Pathways by Gemfibrozil in Predementia Alzheimer Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Preclinical Alzheimer's Disease
Keywords: Alzheimer disease
mild cognitive impairment
normal cognition
Lead sponsor: University of Kentucky
Sponsor class: OTHER
First posted: 2014-01-24
Enrollment: 72
Sex: ALL
Minimum age (years): 65
Maximum age (years): 90
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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

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.

Eligibility 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.

Primary outcomes:
measure: Safety
timeFrame: 52 weeks
measure: microRNA-107 levels
timeFrame: 48 weeks
measure: beta-amyloid levels
timeFrame: 48 weeks
Secondary outcomes:
measure: Free and cued selective reminding test (FCSRT)
timeFrame: 48 weeks
measure: Paired associates learning (PAL)
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
Study officials:
affiliation: University of Kentucky
name: Gregory A Jicha, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: