Exercise, Statins, and the Metabolic Syndrome

This study has been completed.
Sponsor:
Collaborator:
American Heart Association
Information provided by (Responsible Party):
University of Missouri-Columbia
ClinicalTrials.gov Identifier:
NCT01700530
First received: September 26, 2012
Last updated: October 1, 2012
Last verified: October 2012
  Purpose

The metabolic syndrome (MSynd) as recently defined by Grundy et al (1) in a position statement from the American Heart Association (AHA) and the National Heart, Lung, and Blood Institute (NHLBI) of the National Institute of Health is "a cluster of interrelated risk factors of metabolic origin -metabolic risk factors - that appear to directly promote the development of atherosclerotic cardiovascular disease (ASCVD)." Grundy et al (1) went on to describe metabolic risk factors as "atherogenic dyslipidemia, elevated blood pressure, and elevated blood glucose." These metabolic risk factors, or some may call physiological or clinical characteristics, appear to greatly increase the risk for ASCVD when they occur at the same time. Grundy et al also state the following about the MSynd "available data suggest that it is a syndrome, ie, a grouping of ASCVD risk factors, but one that probably has more than one cause. Regardless of the cause, the syndrome identifies individuals at risk for ASCVD." Statins (St) dramatically decrease low-density lipoprotein cholesterol (LDL-C) and are the primary treatment for individuals at risk for the MSynd and CVD. Long-term studies indicating that St-treatment has reduced the incidence of CVD by only 30% have placed an emphasis on increasing high-density lipoprotein (HDL-C) levels, which are protective against CVD. Increased physical activity (i.e., exercise) is an effective treatment and may complement St-treatment. Increased physical activity or chronic exercise increases HDL-C and reverses insulin resistance, and thus may complement the effects of St-treatment. Although experts advocate St-treatment and exercise, there is a paucity of research examining their combined impact. In the proposed study, 20 sedentary individuals with the MSynd will be assigned to St-treatment (Simvastatin) (40 mg/day) for 12 weeks or to St-treatment (40 mg/day) plus a monitored exercise regimen (45 min/day @ 5 days/week) for 12 weeks. The hypothesis is that the addition of exercise to St-treatment will provide an additive benefit in lowering clinical measures which are used to diagnose the MSynd according to the AHA and NHBLI. Specifically, we will test these clinical measures: insulin resistance, blood triglycerides and HDL cholesterol, hypertension, and waist circumference. Therefore, this project's Primary Aim is to compare the effects of St-treatment (St) and St-treatment plus exercise (St+Ex) in their ability to favorably change these clinical measurements.

Elevated blood lipid levels can cause an increased storage of intramuscular triglycerides (IMTG) in skeletal muscle, a marker and possible cause of peripheral insulin resistance. Because St-treatment and exercise can lower blood lipids and improve insulin sensitivity, it is important to compare the individual and combinatory impact upon IMTG levels. Therefore, the Secondary Aim will compare the impact of St and St+Ex on IMTG content.

MSynd subjects often display an overactive sympathetic nervous system that may play a causative role in the development of insulin resistance. Previous work shows that both exercise and St-treatment can independently lower overactive sympathetic nervous drive. The final goal of this project is to determine if St + Ex will have a greater impact on lowering sympathetic drive then St treatment alone. Comparing the changes in sympathetic drive with St-treatment will also provide greater information on the associations between overactive sympathetic drive and insulin resistance.


Condition Intervention
Metabolic Syndrome
Obese
Sedentary
Drug: Statin
Other: Exercise only
Other: Statins + Exercise

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Exercise, Statins, and the Metabolic Syndrome

Resource links provided by NLM:


Further study details as provided by University of Missouri-Columbia:

Primary Outcome Measures:
  • Fitness [ Time Frame: Baseline and after 12 weeks of treatment ] [ Designated as safety issue: No ]
    % change in fitness between baseline and after 12 weeks of treatment will be assessed by VO2max


Secondary Outcome Measures:
  • Mitochondrial content in skeletal muscle [ Time Frame: Baseline and after 12 weeks of treatment ] [ Designated as safety issue: No ]
    % change in mitochondrial content between baseline and after 12 weeks of treatment will be assessed in muscle from biopsies

  • Metabolic Syndrome markers [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Fasting glucose Plasma triglycerides and other blood lipids HDL-Cholesterol Waist Circumference Blood Pressure

  • Metabolic Syndrome Markers [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Fasting glucose Plasma triglycerides and other blood lipids HDL-Cholesterol Waist Circumference


Enrollment: 121
Study Start Date: May 2007
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Statin
Statins (40mg/day)for an average of 12 weeks
Drug: Statin
Statins (40mg/day)for 12 weeks
Other Name: simvastatin
Experimental: Exercise only
12 weeks of exercise training (5 days a week for 45-50 min a session)
Other: Exercise only
12 weeks of exercise training (5 days a week for 45-50 min a session)
Other Name: Physical activity
Active Comparator: Statins + Exercise
Statins (40mg/day of simvastatin) plus exercise training (5 days/wk) for 12 weeks
Other: Statins + Exercise
Statins (40mg/day of simvastatin) plus exercise training (5 days/wk for 45-50 min a session) for 12 weeks
Other Name: Statins + Physical Activity

  Eligibility

Ages Eligible for Study:   25 Years to 59 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Sedentary metabolic syndrome subjects will be 25-59 y of age
  • overweight to Class I or II obese (BMI 25-39 kg/m2) men and women
  • 2 of 4 other characteristics of the metabolic syndrome including fasting glucose of 100 to 125 mg/dl; waist circumference greater than 102 cm in men and 88 cm in women, serum triglyceride concentration greater than 150 mg/dl, HDL-C concentrations less than 40 mg/dl in men and 50 mg/dl in women, and blood pressure greater than 130/85 mmHG
  • Women must be taking birth control or be postmenopausal.

Exclusion Criteria:

  • Diagnosed cardiovascular disease or diabetes or disease
  • Symptoms that could alter their ability to perform exercise
  • Fasting blood glucose of greater than 126 mg/dl
  • Smoking
  • Taking any medications or supplements (e.g., statins, fibrates, metformin, thiazolidenediones, anti-hypertensives (ACE-inhibitors and angiotensin blockers) which could affect blood lipids or insulin sensitivity.
  • Women who are pregnant or plan to become pregnant during the duration of the study
  • Individuals exercising regularly (more than one 30 min session per week)
  • Individuals with an orthopedic limitations for walking.
  • Report any allergies to the medications (statins, lidocaine)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01700530

Locations
United States, Missouri
University of Missouri
Columbia, Missouri, United States, 65211
Sponsors and Collaborators
University of Missouri-Columbia
American Heart Association
Investigators
Principal Investigator: John P Thyfault, PhD University of Missouri-Columbia
  More Information

No publications provided

Responsible Party: University of Missouri-Columbia
ClinicalTrials.gov Identifier: NCT01700530     History of Changes
Other Study ID Numbers: 09CRP2260136
Study First Received: September 26, 2012
Last Updated: October 1, 2012
Health Authority: United States:

Keywords provided by University of Missouri-Columbia:
mitochondria
fitness
statins
cholesterol
metabolic syndrome

Additional relevant MeSH terms:
Metabolic Syndrome X
Syndrome
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Disease
Pathologic Processes
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Simvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 19, 2014