Exercise Dose and Metformin for Vascular Health in Metabolic Syndrome

Rutgers The State University of New Jersey

Status and phase: Completed; Phase 3; Phase 2

Conditions: Metabolic Syndrome

Treatments: Drug: Placebo; Behavioral: High Intensity Exercise; Drug: Metformin; Behavioral: Low Intensity Exercise

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03355469

19364

1R01HL130296-01A1 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Enrollment: 91 patients

Sex: All

Ages: 40 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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)

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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91 participants in 4 patient groups, including a placebo group

LoEx with Placebo

Placebo Comparator group

Description:

Low intensity exercise with placebo.

Treatment:

Behavioral: Low Intensity Exercise

Drug: Placebo

HiEx with Placebo

Placebo Comparator group

Description:

High intensity exercise with placebo.

Treatment:

Behavioral: High Intensity Exercise

Drug: Placebo

LoEx with Metformin

Active Comparator group

Description:

Low intensity exercise with metformin.

Treatment:

Behavioral: Low Intensity Exercise

Drug: Metformin

HiEx with Metformin

Active Comparator group

Description:

High intensity exercise with metformin.

Treatment:

Drug: Metformin

Behavioral: High Intensity Exercise