Exercise Dose and Metformin for Vascular Health in Adults With Metabolic Syndrome

• Status: Recruiting
• Trial end date: 2025-05-01
• Target enrollment: 0
• Participant gender: All

Summary

Arterial disease is the leading cause of morbidity/mortality in Metabolic syndrome (MetS). This occurs early as evidenced by arterial dysfunction that, in turn, raises blood pressure and glucose. 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 risk. However, the optimal exercise dose to be combined with metformin for additive effects on vascular function is unknown. Based on the investigator's preliminary work, the overall hypothesis is that metformin blunts adaptation following high intensity exercise training (HiEx) by lowering mitochondrial derived oxidative stress signaling. The investigators further hypothesize that low intensity exercise (LoEx) training combined with metformin will promote additive effects on vascular function compared to LoEx or HiEx+metformin, and maintain/improve non-exercise physical activity patterns. In this double-blind trial, obese 30-60y MetS participants will be randomized to: 1) LoEx+placebo; 2) LoEx+metformin, 3) HiEx+placebo; or 4) HiEx+metformin for 16 weeks.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Rutgers, The State University of New Jersey
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Metformin

Criteria

Inclusion Criteria:

• Male or female ≥ 40 and ≤ 70 years old

• Has a body mass index ≥ 27 and ≤ 47 kg/m^2

• Not diagnosed with Type 2 diabetes

• Not currently engaged in > 60 min/wk of exercise

• Meet at least 3 of 5 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 (< 40 mg/dl in men, < 50 mg/dl in women), or on medication for treating the condition

• High blood pressure (≥ 130 mmHg systolic or ≥ 85 mmHg diastolic), or on medication for treating the condition

• Elevated fasting glucose (≥ 100 mg/dl), or on medication for treating the condition

Exclusion Criteria:

• Morbidly obese patients (BMI > 47 kg/m^2) and overweight/lean patients (BMI < 27 kg/m^2)

• Evidence of type 1 diabetes and diabetics requiring insulin therapy

• Subjects who have not been weight stable (> 2 kg weight change in past 3 months)

• Subjects who have not been recently active (> 30 min of moderate/high intensity exercise, 2 times/week)

• Subjects who are smokers or who have quit smoking < 5 years ago

• 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 currently taking medications that affect heart rate and rhythm (i.e. calcium-channel blockers, nitrates, alpha- or beta-blockers)

• 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 microbubbles)

• Subjects who are considered non-English speaking individuals