Impact of Statin Therapy on Muscle Mitochondrial Function and Aerobic Capacity

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to test how different doses of a statin, Lipitor, affect muscle health and function, and cardiovascular fitness.

Official Title
-----------------
Impact of Statin Therapy on Muscle Mitochondrial Function and Aerobic Capacity

Conditions
-----------------
Mitochondrial Diseases

Intervention / Treatment
-----------------
* Drug: Lipitor 20Mg Tablet
* Drug: Lipitor 80Mg Tablet
* Drug: Placebo Oral Tablet


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Body mass index (BMI) between 25-43 Weight stable (no more than 5% change in body weight the previous 3 months) >5% risk for a cardiovascular event in the next 10 years according to the 2013 American College of Cardiology/American Heart Association risk calculator and/or 2 out of 5 metabolic syndrome risk factors (Triglycerides ≥ 150 mg/dL; HDL ≤ 40 mg/dL; Glucose ≥ 100mg/dL; Waist Circumference ≥ 102cm for males, 88cm for females; Blood pressure: ≥ 130mmHg systolic and/or 85mmHg diastolic or being treated for hypertension) and/or LDL-Cholesterol >120 mg/dl. Stable doses of medications for 90 days Willing to stop all Nonsteroidal Antiinflammatory Drugs (NSAIDs) and aspirin for 7 days prior to muscle biopsy Exclusion Criteria: Smoking Previous use of statins Use of other medications or supplements that affect lipid profiles or body weight in the last 6 months (e.g., fibric acids, bile acid sequestrants, nicotinic acids, fish oil) Diagnosis of chronic diseases including CVD, other metabolic diseases (e.g., thyroid), current diagnosis and active treatment of cancer, HIV, or acquired immunodeficiency syndrome. Diagnosis of type 1 or type 2 diabetes at the time of screening (fasting blood glucose >126mg/dL). If evidence of type 2 diabetes outcome measures is detected during the course of the study (fasting glucose > 126 mg/dl or HbA1c > 6.5%) we will notify the participant to contact their physician. History of abnormal bleeding problems Currently taking (within the last 10 days) anti-platelet medication (Plavix), Warfarin, and other anti-coagulants (eliquis, pradaxa, and xarelto) medications. >2 fold upper normal limit (UNL) for alanine aminotransferase (ALT) or creatinine Women who are pregnant or breastfeeding Individuals with polymorphisms (SLCO1B1 and GATM) known to be associated with susceptibility for statin induced myopathies (tested at screening) Currently enrolled in another research study

Ages Eligible for Study
-----------------
Minimum Age: 35 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants receiving matching placebo oral tablet. | Drug: Placebo Oral Tablet<br>* Matching placebo pill.<br>* Other names: Placebo;|
| Active Comparator: Low dose statin<br>Participants will receive Lipitor 20Mg Tablet to take daily. | Drug: Lipitor 20Mg Tablet<br>* 20 mg/day pills.<br>* Other names: atorvastatin;|
| Active Comparator: High dose statin<br>Participants will receive Lipitor 80Mg Tablet to take daily. | Drug: Lipitor 80Mg Tablet<br>* 80 mg/day pills.<br>* Other names: atorvastatin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in mitochondrial respiratory function |  | 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| VO2 max |  | 12 Months | 
| Insulin sensitivity |  | 12 Months | 
| Citrate synthase activity |  | 12 Months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
insulin sensitivity, cardiorespiratory fitness, skeletal muscle mitochondrial function