Clinical Trials in the Spotlight Main Page

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) supports a range of clinical trials studying new and existing interventions for prevention and treatment of arthritis, musculoskeletal, and skin diseases.  Investigators supported by the NIAMS need your help finding individuals to participate in clinical trials.  Participating in clinical trials allows you to play an active role as a volunteer in research and contribute to generating new knowledge about the disease/condition, and potentially future treatments.  The information below is designed to help you quickly learn about actively recruiting research studies for which you or someone you know may be eligible. 

Study Description

More than 40 million Americans currently take statins for the treatment or prevention of hyperlipidemia and cardiovascular disease (CVD). Statin therapy is not without risk. Complications include mild to moderate skeletal muscle adverse reactions, with a reported incidence as high as 25%. In addition, statins have been shown to worsen insulin resistance and increase risk for type 2 diabetes. Disturbances in mitochondrial respiratory function have been implicated as a causal factor in these pathologies, but studies to test these potential links have not been conducted in human subjects undergoing statin therapy. Patients taking statins are also commonly advised to exercise regularly to further lower the risk for metabolic and cardiovascular disease.

However, recent evidence suggests that statins can impair important exercise adaptations and that this, again, may occur as a result of statins negatively impacting mitochondria in skeletal muscle. In summary, understanding how long-term statin therapy affects mitochondrial function in skeletal muscle is extremely important clinically, given the critical role skeletal muscle plays in maintaining metabolic and cardiovascular health.

Therefore, the objectives of this study are to determine the impact of statin therapy on skeletal muscle mitochondrial function, cardiorespiratory fitness, and metabolism in humans. Aim 1 will use a longitudinal, repeated measures design to test impact of placebo, 20, and 80 mg/day of atorvastatin therapy on skeletal muscle mitochondrial function, insulin sensitivity, and cardiorespiratory fitness. Aim 2 will determine whether 20 and 80 mg/day of atorvastatin differentially blunt the mitochondrial, metabolic, and cardiorespiratory adaptations to aerobic exercise training. State-of- the-art human studies will be conducted in collaboration between two institutions and will include: comprehensive evaluation of mitochondrial function and content, insulin sensitivity, cardiovascular function, and cardiorespiratory fitness. These studies will provide mechanistic data on statin effects in- vivo and improve clinical knowledge of the cost-to-benefit ratio of statin therapy.

ELIGIBILITY CRITERIA:

Inclusion Criteria:

  • Body mass index (BMI) between 30-39
  • Sedentary (less than 30 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
  • Stable doses of medications for 90 days
  • Willing to stop all Nonsteroidal Anti-inflammatory 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 cardiovascular disease, 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 (SLCO1B1 and GATM) known to be associated with susceptibility for statin induced myopathies (tested at screening)
  • Currently enrolled in another research study
  • Postmenopausal women

Study Design:

Allocation: Randomized

Intervention Model: Parallel Assignment

Masking: Double (Participant, Investigator)

Primary Purpose: Prevention

Study Location(s):

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

East Carolina University, Greenville, North Carolina, United States, 27858

Study Website:

https://clinicaltrials.gov/ct2/show/NCT03351998?term=NCT03351998&rank=1

Last Reviewed: 05/07/2019