Impact of Statin Therapy on Adaptations to Aerobic Exercise

• ClinicalTrials.gov Identifier: NCT03360916
• Recruitment Status: Recruiting
• First Posted: December 4, 2017
• Last Update Posted: April 28, 2021
• Sponsor: University of Kansas Medical Center
• Collaborator: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• Information provided by (Responsible Party): University of Kansas Medical Center

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
Cardiovascular Diseases	Drug: Lipitor 20Mg Tablet; Drug: Lipitor 80Mg Tablet; Drug: Placebo; Behavioral: Exercise Program	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

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Impact of Statin Therapy on Adaptations to Aerobic Exercise
• Actual Study Start Date: February 1, 2018
• Estimated Primary Completion Date: July 1, 2023
• Estimated Study Completion Date: July 1, 2023

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 Name: Atorvastatin; 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 Name: Atorvastatin; 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 :

1. Oxygen Consumption [ Time Frame: 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 :

1. Mitochondrial respiratory function [ Time Frame: Change from Baseline to Week 12 ]
   Mitochondrial respiration will be measured by commercially available O2k Oroboros device.
2. Insulin sensitivity [ Time Frame: 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.
3. Citrate synthase activity [ Time Frame: Change from Baseline to Week 12 ]
   This will be measured by an enzyme activity assay.

Eligibility Criteria

• Ages Eligible for Study: 35 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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
• 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

Contacts and Locations

Contacts

Contact: Clara Amat, MS; 913-945-8834; camatfernandez@kumc.edu

Locations

United States, Kansas

University of Kansas Medical Center; Recruiting

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

More Information

• Responsible Party: University of Kansas Medical Center
• ClinicalTrials.gov Identifier: NCT03360916
• Other Study ID Numbers: STUDY00140791; R01AR071263 ( U.S. NIH Grant/Contract )
• First Posted: December 4, 2017
• Last Update Posted: April 28, 2021
• Last Verified: April 2021

• 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

Keywords provided by University of Kansas Medical Center:

high cholesterol; exercise; statins

Additional relevant MeSH terms:

Cardiovascular Diseases; Atorvastatin; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors