Impact of Statin Therapy on Adaptations to Aerobic Exercise

Study Overview
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Brief Summary
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The purpose of this study is to determine how different doses of a statin affect muscle health and exercise.

Detailed Description
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High cholesterol and cardiovascular disease (CVD) is currently prevented and treated with statin therapy. Statin use can cause muscle weakness, fatigue and/or pain, and these symptoms can increase with dose and duration of statin use. Statins may also change the ability to exercise. This study is testing how different doses of a statin, Lipitor, affect muscle health and exercise. The doses that will be used in this study (20 mg/day or 80 mg/day) are typical for treating high cholesterol. This study is expected to last about 14 weeks.

Official Title
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Impact of Statin Therapy on Adaptations to Aerobic Exercise

Conditions
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Cardiovascular Diseases

Intervention / Treatment
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* Drug: Lipitor 20Mg Tablet
* Drug: Lipitor 80Mg Tablet
* Drug: Placebo
* Behavioral: Exercise Program


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body Mass Index (BMI) between 25-43 kg^m2 Sedentary (less than 150 min of physical activity/week during last 6 months) 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). 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 Use of statins in the last 6 months 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, diabetes, other metabolic diseases (e.g., thyroid), cancer, HIV, or acquired immunodeficiency syndrome 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 known to be associated with susceptibility for statin induced myopathies (tested at screening) Currently enrolled in another research study

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo & Exercise Group<br>Participants randomized to this group will undergo placebo treatment and an aerobic exercise program. | Drug: Placebo<br>* One matching placebo tablet by mouth every day for 12 weeks.<br>Behavioral: Exercise Program<br>* Exercise program of brisk walking and/or slow jogging on a treadmill for 90 minutes of exercise spread over 3 days during week 1, 150 minutes of exercise spread over 5 days during week 2, 225 minutes of exercise over 5 days during week 3 and for the rest of the study.<br>|
| Experimental: Low Statin & Exercise Group<br>Participants randomized to this group will undergo low statin treatment (Lipitor 20Mg Tablet) and an aerobic exercise program. | Drug: Lipitor 20Mg Tablet<br>* One tablet by mouth every day for 12 weeks.<br>* Other names: Atorvastatin;Behavioral: Exercise Program<br>* Exercise program of brisk walking and/or slow jogging on a treadmill for 90 minutes of exercise spread over 3 days during week 1, 150 minutes of exercise spread over 5 days during week 2, 225 minutes of exercise over 5 days during week 3 and for the rest of the study.<br>|
| Experimental: High Statin & Exercise Group<br>Participants randomized to this group will undergo high statin treatment (Lipitor 80Mg Tablet) and an aerobic exercise program. | Drug: Lipitor 80Mg Tablet<br>* One tablet by mouth every day for 12 weeks.<br>* Other names: Atorvastatin;Behavioral: Exercise Program<br>* Exercise program of brisk walking and/or slow jogging on a treadmill for 90 minutes of exercise spread over 3 days during week 1, 150 minutes of exercise spread over 5 days during week 2, 225 minutes of exercise over 5 days during week 3 and for the rest of the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxygen Consumption | Changes in cardiorespiratory fitness measured by oxygen consumption during increased exercise on a motorized treadmill and during lower intensity exercise sessions. Oxygen consumption will be measured at peak and at various time points to determine fitness. | Change from Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mitochondrial respiratory function | Mitochondrial respiration will be measured by commercially available O2k Oroboros device. | Change from Baseline to Week 12 | 
| Insulin sensitivity | Insulin sensitivity will be measured by a standardized intravenous glucose tolerance test (IVGTT) in which glucose and insulin responses are monitored following glucose infusion. | Change from Baseline to Week 12 | 
| Citrate synthase activity | This will be measured by an enzyme activity assay. | Change from Baseline to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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high cholesterol, exercise, statins