Cardiovascular Diseases
Conditions
Keywords
high cholesterol, exercise, statins
Brief summary
The purpose of this study is to determine how different doses of a statin affect muscle health and exercise.
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.
Interventions
One tablet by mouth every day for 12 weeks.
One tablet by mouth every day for 12 weeks.
DRUGPlacebo
One matching placebo tablet by mouth every day for 12 weeks.
BEHAVIORALExercise 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.
Sponsors
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
University of Kansas Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
35 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Difference in Mitochondrial Respiratory Function | Value at 3 months minus value at baseline |
Secondary
| Measure | Time frame |
|---|---|
| Change in VO2 Max | Value at 12 months minus value at baseline |
Countries
United States
Participant flow
Pre-assignment details
All 52 participants that were officially enrolled were randomized
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants receiving matching placebo oral tablet.
Placebo Oral Tablet: Matching placebo pill. | 16 |
| Low Dose Statin Participants receiving Lipitor 20Mg Tablet to take daily.
Lipitor 20Mg Tablet: 20 mg/day pills. | 17 |
| High Dose Statin Participants receiving Lipitor 80Mg Tablet to take daily.
Lipitor 80Mg Tablet: 80 mg/day pills. | 19 |
| Total | 52 |
Baseline characteristics
| Characteristic | Placebo | Low Dose Statin | High Dose Statin | Total |
|---|---|---|---|---|
| Age, Continuous | 50.13 years STANDARD_DEVIATION 8.29 | 51.28 years STANDARD_DEVIATION 9.04 | 50.85 years STANDARD_DEVIATION 7.96 | 50.78 years STANDARD_DEVIATION 8.28 |
| BMI | 34.68 kg/m^2 STANDARD_DEVIATION 4.58 | 35.43 kg/m^2 STANDARD_DEVIATION 5.14 | 34.55 kg/m^2 STANDARD_DEVIATION 4.84 | 34.88 kg/m^2 STANDARD_DEVIATION 4.79 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 3 Participants | 4 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 13 Participants | 14 Participants | 37 Participants |
| Region of Enrollment United States | 16 participants | 17 participants | 19 participants | 52 participants |
| Relative Peak VO2 Max | 25.29 mL/kg/min STANDARD_DEVIATION 6.21 | 21.30 mL/kg/min STANDARD_DEVIATION 6.27 | 22.74 mL/kg/min STANDARD_DEVIATION 5.74 | 22.97 mL/kg/min STANDARD_DEVIATION 6.15 |
| Sex: Female, Male Female | 12 Participants | 13 Participants | 15 Participants | 40 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 4 Participants | 12 Participants |
| Total Cholesterol | 200.19 mg/dL STANDARD_DEVIATION 31.63 | 220.33 mg/dL STANDARD_DEVIATION 38.54 | 204.90 mg/dL STANDARD_DEVIATION 32.24 | 208.65 mg/dL STANDARD_DEVIATION 34.72 |
| Weight | 94.74 kg STANDARD_DEVIATION 16.15 | 103.42 kg STANDARD_DEVIATION 20.06 | 95.83 kg STANDARD_DEVIATION 14.33 | 98.10 kg STANDARD_DEVIATION 17.08 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 17 | 0 / 19 |
| other Total, other adverse events | 3 / 16 | 5 / 17 | 8 / 19 |
| serious Total, serious adverse events | 0 / 16 | 0 / 17 | 0 / 19 |
Outcome results
Primary
Difference in Mitochondrial Respiratory Function
Time frame: Value at 3 months minus value at baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Difference in Mitochondrial Respiratory Function | 2.29 pmols/s/mg | Standard Deviation 125.59 |
| Low Dose Statin | Difference in Mitochondrial Respiratory Function | -11.24 pmols/s/mg | Standard Deviation 130.12 |
| High Dose Statin | Difference in Mitochondrial Respiratory Function | 44.88 pmols/s/mg | Standard Deviation 105.19 |
p-value: 0.953t-test, 2 sided
p-value: 0.7908t-test, 2 sided
p-value: 0.1344t-test, 2 sided
Secondary
Change in VO2 Max
Time frame: Value at 12 months minus value at baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in VO2 Max | 0.22 L/min | Standard Deviation 0.18 |
| Low Dose Statin | Change in VO2 Max | 0.23 L/min | Standard Deviation 0.21 |
| High Dose Statin | Change in VO2 Max | 0.21 L/min | Standard Deviation 0.23 |
p-value: 0.0005t-test, 2 sided
p-value: 0.0021t-test, 2 sided
p-value: 0.0025t-test, 2 sided