Exercise Dose-Response on Features of the Metabolic Syndrome

Study Overview
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Brief Summary
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This study investigates the degree of improvement in insulin resistance and features of the metabolic syndrome in non-diabetic overweight or obese subjects after training in a low-intensity, moderate-intensity or non-aerobic exercise program, as well as self-initiated exercise behavior after the assigned exercise program.

Detailed Description
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The proposed study is a randomized, open study comparing low-intensity and moderate-intensity aerobic exercise versus non-aerobic (stretching) exercise on direct measurements of insulin resistance and variables associated with the metabolic syndrome. This 6-month intervention will be followed by an additional 6-month follow-up period during which subjects will be encouraged to maintain their exercise regimen (along with their prescribed diet) but without scheduled supervision. Behavioral variables associated with adherence will be analyzed along with changes in the above physiological variables.

Official Title
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Dose-Response Effects of Aerobic Exercise on Insulin Sensitivity and the Metabolic Syndrome

Conditions
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Insulin Resistance, Metabolic Syndrome, Obesity

Intervention / Treatment
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* Behavioral: Low-intensity treadmill exercise
* Behavioral: Moderate-intensity treadmill exercise
* Behavioral: Non-aerobic stretching exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females, age 18-60 At least 2 of the 5 components of the NCEP definition of the metabolic syndrome, provided that either the triglyceride or waist circumference criteria are met Body mass index of 25-45 kg/m2 Subjects not currently following a regular exercise program nor an optimal diet, and who self-report their activity level as sedentary Able to understand and sign the informed consent form, follow the instructions given in the study, attend all necessary clinic visits, and undergo all required study procedures Exclusion Criteria: Past or current diabetes mellitus Significant concurrent medical illnesses (chronic liver or renal disease, malignancies, recent or chronic infections including HIV, surgeries or other hospitalizations within four weeks prior to screening), uncontrolled hypertension (BP >160/90 mm Hg), or abnormal TSH on screening. Conditions that may contraindicate physical activity (clinically significant cardiac, pulmonary, orthopedic, rheumatological or neurological diseases) Cardiovascular disease not controlled with medical therapy, or invasive vascular procedures within six months prior to screening Subjects found on resting EKG or stress testing to have underlying cardiac abnormalities Perimenopausal women who are experiencing irregular menses Pregnant or lactating women Subjects who may have limited exercise tolerance because of treatment with β-adrenergic blockade agents, at least until agents of alternate drug classes can be substituted Subjects with concurrent endocrinopathies Subjects receiving concurrent treatment with metformin, thiazolidinediones, systemic glucocorticoids, or any weight loss agents Subjects who expect to require medications during the course of the study that may affect their metabolic profile, including systemic glucocorticoids and hormone replacement therapies Subjects who cannot complete the stress test due to physical limitations Any other factors that, in the opinion of the investigators, may interfere with the safe conduct, the successful completion, or the quality of the data obtained from the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: 1<br>Low-intensity aerobic exercise | Behavioral: Low-intensity treadmill exercise<br>* Treadmill walking at 30% of VO2Reserve, 3-5 times per week at 20-60 minutes per session, progressive.<br>* Other names: Casual walking program;|
| Experimental: 2<br>Moderate-intensity aerobic exercise | Behavioral: Moderate-intensity treadmill exercise<br>* Treadmill walking at 60% of VO2Reserve, 3-5 times per week at 20-60 minutes per session, progressive.<br>* Other names: Brisk walking program;|
| Active Comparator: 3<br>Non-aerobic stretching exercise | Behavioral: Non-aerobic stretching exercise<br>* Floor stretching exercise, 3-5 times per week at 20-60 minutes duration per session, progressive.<br>* Other names: Non-aerobic control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin sensitivity (clamp) |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aerobic fitness (VO2Max, Anaerobic threshold, endurance time) |  | 6 and 12 months | 
| Body mass index, waist circumference |  | 6 and 12 months | 
| Fat mass, fat-free mass, lean body mass (DEXA) |  | 6 and 12 months | 
| Blood pressure |  | 6 and 12 months | 
| Fasting glucose, hemoglobin A1c, glucose 2 hours post-oral glucose tolerance test, HOMA-IR index |  | 6 and 12 months | 
| Fasting lipid profile |  | 6 and 12 months | 
| Apolipoprotein B |  | 6 and 12 months | 
| Highly-sensitive C-reactive protein |  | 6 and 12 months | 
| Exercise behavior questionnaire scores |  | 6 and 12 months | 
| Any adverse events |  | 6 and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Insulin resistance, Metabolic syndrome, Aerobic exercise, Exercise behavior