Exercise Dose and Metformin for Vascular Health in Adults With Metabolic Syndrome
Overview
- Phase
- Phase 2
- Intervention
- Placebo
- Conditions
- Metabolic Syndrome
- Sponsor
- Rutgers University
- Enrollment
- 91
- Locations
- 1
- Primary Endpoint
- Change in Fasting Unscaled Flow Mediated Dilation (FMD) of the Brachial Artery
- Status
- Completed
- Last Updated
- 7 months ago
Overview
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.
Investigators
Steven K Malin, PhD
Principal Investigator
Rutgers University
Eligibility Criteria
Inclusion Criteria
- •Male or female ≥40 and ≤80 years old.
- •Has a body mass index ≥25 and ≤47 kg/m
- •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
Exclusion Criteria
- •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
Arms & Interventions
LoEx with Placebo
Low intensity exercise with placebo.
Intervention: Placebo
LoEx with Placebo
Low intensity exercise with placebo.
Intervention: Low Intensity Exercise
HiEx with Placebo
High intensity exercise with placebo.
Intervention: Placebo
HiEx with Placebo
High intensity exercise with placebo.
Intervention: High Intensity Exercise
LoEx with Metformin
Low intensity exercise with metformin.
Intervention: Metformin
LoEx with Metformin
Low intensity exercise with metformin.
Intervention: Low Intensity Exercise
HiEx with Metformin
High intensity exercise with metformin.
Intervention: Metformin
HiEx with Metformin
High intensity exercise with metformin.
Intervention: High Intensity Exercise
Outcomes
Primary Outcomes
Change in Fasting Unscaled Flow Mediated Dilation (FMD) of the Brachial Artery
Time Frame: 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 Outcomes
- Change in Metabolic Insulin Sensitivity. Glucose Infusion Rate Normalized to Steady-State Insulin (GIR).(0 and 16 weeks)
- Change in Fasting Augmentation Index(0 and 16 weeks)
- Change in Insulin-stimulated Microvascular Blood Flow (MBF) of the Forearm.(0 and 16 weeks)
- Change in Insulin-stimulated Microvascular Flow Velocity (MFV) of the Forearm.(0 and 16 weeks)
- Change in Insulin-stimulated Microvascular Blood Volume (MBV) of the Forearm.(0 and 16 weeks)