Mitochondrial Diseases
Conditions
Keywords
insulin sensitivity, cardiorespiratory fitness, skeletal muscle mitochondrial function
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.
Interventions
20 mg/day pills.
80 mg/day pills.
DRUGPlacebo Oral Tablet
Matching placebo pill.
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 * 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Difference in Mitochondrial Respiratory Function | value at 12 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 68 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. | 23 |
| Low Dose Statin Participants will receive Lipitor 20Mg Tablet to take daily.
Lipitor 20Mg Tablet: 20 mg/day pills. | 24 |
| High Dose Statin Participants will receive Lipitor 80Mg Tablet to take daily.
Lipitor 80Mg Tablet: 80 mg/day pills. | 21 |
| Total | 68 |
Baseline characteristics
| Characteristic | Placebo | Low Dose Statin | High Dose Statin | Total |
|---|---|---|---|---|
| Age, Continuous | 52.98 years STANDARD_DEVIATION 8.28 | 54.53 years STANDARD_DEVIATION 7.66 | 54.10 years STANDARD_DEVIATION 7.14 | 53.87 years STANDARD_DEVIATION 7.64 |
| BMI | 32.96 kg/m^2 STANDARD_DEVIATION 4.55 | 31.14 kg/m^2 STANDARD_DEVIATION 3.74 | 32.31 kg/m^2 STANDARD_DEVIATION 4.98 | 32.12 kg/m^2 STANDARD_DEVIATION 4.43 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 3 Participants | 6 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 | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) White | 20 Participants | 23 Participants | 16 Participants | 59 Participants |
| Region of Enrollment United States | 23 participants | 24 participants | 21 participants | 68 participants |
| Relative Peak VO2 Max | 24.12 mL/kg/min STANDARD_DEVIATION 5.7 | 25.53 mL/kg/min STANDARD_DEVIATION 6.97 | 24.92 mL/kg/min STANDARD_DEVIATION 5.12 | 24.87 mL/kg/min STANDARD_DEVIATION 5.96 |
| Sex: Female, Male Female | 16 Participants | 17 Participants | 16 Participants | 49 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 5 Participants | 19 Participants |
| Total Cholesterol | 199.65 mg/dL STANDARD_DEVIATION 38.82 | 211.75 mg/dL STANDARD_DEVIATION 41.68 | 214.33 mg/dL STANDARD_DEVIATION 33.53 | 208 mg/dL STANDARD_DEVIATION 38.32 |
| Weight | 93.79 kg STANDARD_DEVIATION 13.89 | 90.60 kg STANDARD_DEVIATION 15.87 | 89.28 kg STANDARD_DEVIATION 15.22 | 91.27 kg STANDARD_DEVIATION 14.92 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 24 | 0 / 21 |
| other Total, other adverse events | 15 / 23 | 17 / 24 | 14 / 21 |
| serious Total, serious adverse events | 1 / 23 | 0 / 24 | 0 / 21 |
Outcome results
Primary
Difference in Mitochondrial Respiratory Function
Time frame: value at 12 months minus value at baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Difference in Mitochondrial Respiratory Function | 36 pmols/s/mg | Standard Deviation 366 |
| Low Dose Statin | Difference in Mitochondrial Respiratory Function | 32 pmols/s/mg | Standard Deviation 213 |
| High Dose Statin | Difference in Mitochondrial Respiratory Function | -3 pmols/s/mg | Standard Deviation 180 |
p-value: 0.6051signed rank test
p-value: 0.9434signed rank test
p-value: 0.9408t-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 | -0.2 L/min | Standard Deviation 0.23 |
| Low Dose Statin | Change in VO2 Max | 0.03 L/min | Standard Deviation 0.16 |
| High Dose Statin | Change in VO2 Max | -0.06 L/min | Standard Deviation 0.18 |
p-value: 0.7458t-test, 2 sided
p-value: 0.4056t-test, 2 sided
p-value: 0.1932t-test, 2 sided