Impact of Statin Therapy on Muscle Mitochondrial Function and Aerobic Capacity

• ClinicalTrials.gov Identifier: NCT03351998
• Recruitment Status: Recruiting
• First Posted: November 24, 2017
• Last Update Posted: November 6, 2019
• 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 test how different doses of a statin, Lipitor, affect muscle health and function, and cardiovascular fitness.

Condition or disease	Intervention/treatment	Phase
Mitochondrial Diseases	Drug: Lipitor 20Mg Tablet; Drug: Lipitor 80Mg Tablet; Drug: Placebo Oral Tablet	Phase 4

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 Muscle Mitochondrial Function and Aerobic Capacity
• Actual Study Start Date: February 22, 2018
• Estimated Primary Completion Date: July 1, 2022
• Estimated Study Completion Date: July 1, 2022

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; Participants receiving matching placebo oral tablet.	Drug: Placebo Oral Tablet; Matching placebo pill.; Other Name: Placebo
Active Comparator: Low dose statin; Participants will receive Lipitor 20Mg Tablet to take daily.	Drug: Lipitor 20Mg Tablet; 20 mg/day pills.; Other Name: atorvastatin
Active Comparator: High dose statin; Participants will receive Lipitor 80Mg Tablet to take daily.	Drug: Lipitor 80Mg Tablet; 80 mg/day pills.; Other Name: atorvastatin

Outcome Measures

Primary Outcome Measures :

1. Difference in mitochondrial respiratory function [ Time Frame: 12 Months ]

Secondary Outcome Measures :

1. VO2 max [ Time Frame: 12 Months ]
2. Insulin sensitivity [ Time Frame: 12 Months ]
3. Citrate synthase activity [ Time Frame: 12 Months ]

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
• 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

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

United States, North Carolina

East Carolina University; Recruiting

Greenville, North Carolina, United States, 27858

Contact: Patty Brophy

Principal Investigator: Darrell Neufer, PhD

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: NCT03351998
• Other Study ID Numbers: STUDY00140789; R01AR071263 ( U.S. NIH Grant/Contract )
• First Posted: November 24, 2017
• Last Update Posted: November 6, 2019
• Last Verified: November 2019

• 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:

insulin sensitivity; cardiorespiratory fitness; skeletal muscle mitochondrial function

Additional relevant MeSH terms:

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