Impact of Statin Therapy on Muscle Mitochondrial Function and Aerobic Capacity

NCT03351998 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: STUDY00140789R01AR071263
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 2

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.

Conditions

Mitochondrial Diseases

Keywords

insulin sensitivity; cardiorespiratory fitness; skeletal muscle mitochondrial function

Outcome Measures

Primary Outcomes (1)

• Difference in Mitochondrial Respiratory Function

  value at 12 months minus value at baseline

Secondary Outcomes (1)

• Change in VO2 Max

  value at 12 months minus value at baseline

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Participants receiving matching placebo oral tablet.

Drug: Placebo Oral Tablet

Low dose statin

ACTIVE COMPARATOR

Participants will receive Lipitor 20Mg Tablet to take daily.

Drug: Lipitor 20Mg Tablet

High dose statin

ACTIVE COMPARATOR

Participants will receive Lipitor 80Mg Tablet to take daily.

Drug: Lipitor 80Mg Tablet

Interventions

Lipitor 20Mg Tablet DRUG

20 mg/day pills.

Also known as: atorvastatin

Low dose statin

Lipitor 80Mg Tablet DRUG

80 mg/day pills.

Also known as: atorvastatin

High dose statin

Placebo Oral Tablet DRUG

Matching placebo pill.

Also known as: Placebo

Placebo

Eligibility Criteria

• Age: 35 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Kansas Medical Center: lead
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator

Study Sites (2)

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

East Carolina University

Greenville, North Carolina, 27858, United States

Location

MeSH Terms

Conditions

Mitochondrial Diseases; Insulin Resistance

Interventions

Atorvastatin; Tablets

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases; Hyperinsulinism; Glucose Metabolism Disorders

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Dosage Forms; Pharmaceutical Preparations

Limitations and Caveats

The COVID-19 epidemic started in the middle of the trial forcing us to stop recruitment for four months. Furthermore, the continuation of the pandemic slowed recruitment for the rest of the trial and significantly impacted n size. There was also a national dextrose shortage following a hurricane in Puerto Rico. As a result many of the IVGTT were not conducted.

Results Point of Contact

• Title: John P. Thyfault
• Organization: University of Kansas Medical Center

jthyfault@kumc.edu

913-588-1790

Study Officials

• John Thyfault, PhD

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2017
• First Posted: November 24, 2017
• Study Start: February 22, 2018
• Primary Completion: July 7, 2023
• Study Completion: July 7, 2023
• Last Updated: December 18, 2024
• Results First Posted: December 18, 2024

Record last verified: 2024-11

Locations

US (2)