Exercise Dose and Metformin for Vascular Health in Metabolic Syndrome
- Conditions
- Metabolic Syndrome
- Interventions
- Registration Number
- NCT03355469
- Lead Sponsor
- Rutgers University
- Brief Summary
Health organizations recommend exercise in an intensity based manner to promote cardiovascular adaptation and prevent disease. Metformin is a common anti-diabetes medication that reduces future type 2 diabetes and cardiovascular disease (CVD) risk. However, the optimal dose of exercise to be combined with metformin for vascular health remains unknown. The purpose of this study is to evaluate whether combining high or low intensity exercise with metformin has the potential to outperform either exercise intensity alone on blood flow across the arterial tree as well as impact insulin action in individuals with metabolic syndrome. Identification of such outcomes will indicate 1) whether and how metformin should be combined with physical activity for CVD prevention, 2) provide the first indication of whether exercise intensity reduces CVD risk via multi-level vasculature function vs. metabolic insulin action, and 3) provide a rational early treatment for people with metabolic syndrome to prevent/treat type 2 diabetes and CVD.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 91
- Male or female ≥40 and ≤80 years old.
- Has a body mass index ≥25 and ≤47 kg/m2.
- Not diagnosed with Type 2 or Type 1 diabetes
- Not currently engaged in > 150 min/wk of exercise
- Weight stable (<2kg weight change in past 3 months)
- Non-smoking >5 years
At minimum, subject will have abdominal obesity (increased waist circumference as defined below) and may have any additional National Cholesterol Education Adult Treatment Panel III Metabolic Syndrome criteria:
- Increased waist circumference (≥102 cm in men; ≥88 cm in women)
- Elevated triglycerides (≥150 mg/dl), or on medication for treating the condition
- Reduced HDL-cholesterol (<40mg/dl in men, <50 mg/dl in women), or on medication for treating the condition
- High blood pressure (≥130 mmHg systolic or ≥85mmHg diastolic), or on medication for treating the condition
- Elevated fasting glucose (≥100 mg/dl), or on medication for treating the condition
- Other major risk factors to be noted based on the Framingham Risk Score
- HbA1c 5.7-6.4%
- LDL > 130 mg/dL
- Family history of type 2 diabetes (immediate family, i.e. parent/sibling)
- History of gestational diabetes
- History of Polycystic Ovarian Syndrome
- Family history of pre-mature cardiovascular disease (immediate family i.e. parent/sibling) before 55 for males or 65 for females that can include heart attack, peripheral arterial disease, abdominal aortic aneurysm, symptomatic carotid artery disease or clinical coronary heart disease)
- Age ( > 45 years old for men; > 55 years old for women)
- Black/African American, Mexican, Asian, and/or Hispanic
- Subjects currently taking medications that affect heart rate and rhythm (i.e. Ca++ channel blockers, nitrates, alpha- or beta-blockers)
- Subjects prescribed metformin or have taken metformin within 1 year.
- Subjects with abnormal estimated glomerular filtration rate (eGFR).
- Hypertriglyceridemic (>400 mg/dl) and hypercholesterolemic (>260 mg/dl) subjects
- Hypertensive (>160/100 mmHg)
- Subjects with a history of significant metabolic, cardiac, congestive heart failure, cerebrovascular, hematological, pulmonary, gastrointestinal, liver, renal, or endocrine disease or cancer that in the investigator's opinion would interfere with or alter the outcome measures, or impact subject safety.
- Pregnant (as evidenced by positive pregnancy test) or nursing women
- Subjects with contraindications to participation in an exercise training program
- Currently taking active weight suppression medication (e.g. phentermine,orlistat, lorcaserin, naltrexone-bupropion in combination, liraglutide, benzphetamine, diethylpropion, phendimetrazine)
- Known hypersensitivity to perflutren (contained in Definity)
- Subjects who are considered non-English speaking individuals
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description LoEx with Placebo Placebo Low intensity exercise with placebo. LoEx with Placebo Low Intensity Exercise Low intensity exercise with placebo. HiEx with Placebo Placebo High intensity exercise with placebo. HiEx with Placebo High Intensity Exercise High intensity exercise with placebo. LoEx with Metformin Metformin Low intensity exercise with metformin. LoEx with Metformin Low Intensity Exercise Low intensity exercise with metformin. HiEx with Metformin Metformin High intensity exercise with metformin. HiEx with Metformin High Intensity Exercise High intensity exercise with metformin.
- Primary Outcome Measures
Name Time Method Change in Fasting Unscaled Flow Mediated Dilation (FMD) of the Brachial Artery 0 and 16 weeks Endothelial function assessed as a percentage change in brachial artery diameter from baseline to deflation (5 minutes after artery occlusion by blood pressure cuff inflation). Delta = Week 16 - Week 0. Higher values and positive change scores following the intervention indicate a better outcome.
- Secondary Outcome Measures
Name Time Method Change in Metabolic Insulin Sensitivity. Glucose Infusion Rate Normalized to Steady-State Insulin (GIR). 0 and 16 weeks The glucose infusion rate (mg/kg/min) divided by steady-state insulin (uU/mL) during a 120 minute euglycemic-hyperinsulinemic clamp provides an index of metabolic insulin sensitivity. Delta = Week 16 - Week 0. Higher values and positive change scores following the intervention indicate a better outcome.
Change in Fasting Augmentation Index 0 and 16 weeks Measure of Arterial Stiffness calculated by dividing the augmentation pressure by the pulse pressure, then multiplying by 100 and normalizing to a heart rate of 75 bpm (AIx75). Delta = Week 16 - Week 0. Lower values and negative change scores following the intervention indicate a better outcome.
Change in Insulin-stimulated Microvascular Blood Flow (MBF) of the Forearm. 0 and 16 weeks Product of microvascular blood volume (VI; video intensity units) and microvascular flow velocity (sec\^-1). Insulin-stimulated microvascular blood flow is the change during a 120 minute euglycemic-hyperinsulinemic clamp (120-0 minutes). Delta = Week 16 - Week 0. Higher values and positive change scores following the intervention indicate a better outcome.
Change in Insulin-stimulated Microvascular Flow Velocity (MFV) of the Forearm. 0 and 16 weeks Replenishment curves of the forearm flexor muscle acquired during steady-state infusion of Definity microbubbles. Insulin-stimulated microvascular flow velocity is the change during a 120 minute euglycemic-hyperinsulinemic clamp (120-0 minutes). Delta = Week 16 - Week 0. Higher values and positive change scores following the intervention indicate a better outcome.
Change in Insulin-stimulated Microvascular Blood Volume (MBV) of the Forearm. 0 and 16 weeks Replenishment curves of the forearm flexor muscle acquired during steady-state infusion of Definity microbubbles. Insulin-stimulated microvascular blood volume is the change during a 120 minute euglycemic-hyperinsulinemic clamp (120-0 minutes). Delta = Week 16 - Week 0. Higher values and positive change scores following the intervention indicate a better outcome.
Trial Locations
- Locations (1)
Rutgers University Loree Gymnasium
🇺🇸New Brunswick, New Jersey, United States
Rutgers University Loree Gymnasium🇺🇸New Brunswick, New Jersey, United States