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: Active, not recruiting
• 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): 119
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Audrey McCalley, MPH; Phone Number: 913-945-8834; Email: amccalley@kumc.edu

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 33 years to 63 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	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

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 (Estimated): May 30, 2024
• Study Completion (Estimated): May 30, 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 (Estimated): December 8, 2023
• Last Update Submitted That Met QC Criteria: December 6, 2023
• Last Verified: December 1, 2023

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