Exercise, Statins, and the Metabolic Syndrome

Study Overview
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Brief Summary
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Here we tested if statins or exercise plus statins had a greater capacity to lower metabolic syndrome risk factors in sedentary individuals with at least 2 metabolic syndrome risk factors. We also examined if statins impacted exercise response for mitochondrial content in muscle or aerobic fitness.

Detailed Description
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OBJECTIVES: Determine if simvastatin impairs exercise training adaptations. BACKGROUND: Statins are commonly prescribed in combination with therapeutic lifestyle changes, including exercise, to reduce cardiovascular disease risk in patients with the metabolic syndrome. Statin use has been linked to skeletal muscle myopathy and impaired mitochondrial function, but it is unclear whether statin use alters adaptations to exercise training. METHODS: We examined the effects of simvastatin on changes in cardiorespiratory fitness and skeletal muscle mitochondrial content in response to aerobic exercise training. Sedentary overweight or obese adults with at least 2 metabolic syndrome risk factors (defined according to National Cholesterol Education Panel Adult Treatment Panel III criteria) were randomized to 12 weeks of aerobic exercise training or to exercise in combination with simvastatin (40 mg per day). The primary outcomes were cardiorespiratory fitness and skeletal muscle (vastus lateralis) mitochondrial content (citrate synthase enzyme activity).

Official Title
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Exercise, Statins, and the Metabolic Syndrome

Conditions
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Obese, Metabolic Syndrome, Sedentary

Intervention / Treatment
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* Drug: Statin
* Other: Exercise only
* Other: Statins + Exercise


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Statin<br>Statins (40mg/day)for an average of 12 weeks | Drug: Statin<br>* Statins (40mg/day)for 12 weeks<br>* Other names: simvastatin;|
| Experimental: Exercise only<br>12 weeks of exercise training (5 days a week for 45-50 min a session) | Other: Exercise only<br>* 12 weeks of exercise training (5 days a week for 45-50 min a session)<br>* Other names: Physical activity;|
| Active Comparator: Statins + Exercise<br>Statins (40mg/day of simvastatin) plus exercise training (5 days/wk) for 12 weeks | Other: Statins + Exercise<br>* Statins (40mg/day of simvastatin) plus exercise training (5 days/wk for 45-50 min a session) for 12 weeks<br>* Other names: Statins + Physical Activity;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| % Change in VO2max (Fitness) | % change in fitness between baseline and after 12 weeks of treatment will be assessed by VO2max | Change from Baseline to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Skeletal Muscle Mitochondrial Content (Citrate Synthase Enzyme Activity) | % change in skeletal muscle mitochondrial content (measured by citrate synthase enzyme activity) from pre to post intervention | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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statins, mitochondria, fitness, cholesterol, metabolic syndrome