Impact of Statin Therapy on Adaptations to Aerobic Exercise

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

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases
• Intervention / Treatment: Drug: Placebo; Behavioral: Exercise Program; Drug: Lipitor 20Mg Tablet; Drug: Lipitor 80Mg Tablet

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 Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 31 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / 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.	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.; Drug: Lipitor 20Mg Tablet; One tablet by mouth every day for 12 weeks.; Other Names: Atorvastatin
Experimental: High Statin & Exercise Group; Participants randomized to this group will undergo high statin treatment (Lipitor 80Mg Tablet) and an aerobic exercise program.	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.; Drug: Lipitor 80Mg Tablet; One tablet by mouth every day for 12 weeks.; Other Names: Atorvastatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Difference in Mitochondrial Respiratory Function	Value at 3 months minus value at baseline

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in VO2 Max	Value at 12 months minus value at baseline

Collaborators and Investigators

• Sponsor: University of Kansas Medical Center
• Collaborators: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• Investigators: Principal Investigator: John Thyfault, PhD, University of Kansas Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2018
• Primary Completion (Actual): June 5, 2024
• Study Completion (Actual): June 5, 2024

Study Registration Dates

• First Submitted: November 20, 2017
• First Submitted That Met QC Criteria: December 1, 2017
• First Posted (Actual): December 4, 2017

Study Record Updates

• Last Update Posted (Actual): April 15, 2025
• Last Update Submitted That Met QC Criteria: April 14, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: exercise; statins; high cholesterol
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: STUDY00140791; R01AR071263 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No