Impact of Statin Therapy on Adaptations to Aerobic Exercise
Study Details
Study Description
Brief Summary
The purpose of this study is to determine how different doses of a statin affect muscle health and exercise.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo & Exercise Group Participants randomized to this group will undergo placebo treatment and an aerobic exercise program. |
Drug: Placebo
One matching placebo tablet by mouth every day for 12 weeks.
Behavioral: Exercise Program
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.
|
| Experimental: Low Statin & Exercise Group Participants randomized to this group will undergo low statin treatment (Lipitor 20Mg Tablet) and an aerobic exercise program. |
Drug: Lipitor 20Mg Tablet
One tablet by mouth every day for 12 weeks.
Other Names:
Behavioral: Exercise Program
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.
|
| Experimental: High Statin & Exercise Group Participants randomized to this group will undergo high statin treatment (Lipitor 80Mg Tablet) and an aerobic exercise program. |
Drug: Lipitor 80Mg Tablet
One tablet by mouth every day for 12 weeks.
Other Names:
Behavioral: Exercise Program
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.
|
Outcome Measures
Primary Outcome Measures
- Oxygen Consumption [Change from Baseline to Week 12]
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.
Secondary Outcome Measures
- Mitochondrial respiratory function [Change from Baseline to Week 12]
Mitochondrial respiration will be measured by commercially available O2k Oroboros device.
- Insulin sensitivity [Change from Baseline to Week 12]
Insulin sensitivity will be measured by a standardized intravenous glucose tolerance test (IVGTT) in which glucose and insulin responses are monitored following glucose infusion.
- Citrate synthase activity [Change from Baseline to Week 12]
This will be measured by an enzyme activity assay.
Eligibility Criteria
Criteria
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
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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)
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Currently enrolled in another research study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Kansas Medical Center | Kansas City | Kansas | United States | 66160 |
Sponsors and Collaborators
- University of Kansas Medical Center
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Investigators
- Principal Investigator: John Thyfault, PhD, University of Kansas Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- STUDY00140791
- R01AR071263