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Impact of Acute Exercise on Vascular Insulin Sensitivity in Metabolic Syndrome

Primary Purpose

Metabolic Syndrome, Obesity

Status

Unknown status

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Single Bout of Exercise

Control Condition

About this trial

This is an interventional prevention trial for Metabolic Syndrome focused on measuring Acute Exercise, Endothelial Function, Simple Obesity, Metabolic Syndrome

Eligibility Criteria

40 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Males and females, ages 40-70 years
Never diagnosed with type 2 diabetes and/or cardiovascular disease
Not currently engaged in > 60 min/wk of exercise
Inclusion criteria specific to health obese vs. metabolic syndrome potential participants:
- Healthy Obese: (BMI ≥ 30 kg/m2 but ≤ 45 kg/m2) and no other metabolic syndrome risk factors, excluding waist circumference.
- Metabolic Syndrome: (BMI ≥ 30 kg/m2 but ≤ 45 kg/m2) and must meet at least 3 out 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 currently taking medication (Rx) Reduced HDL-cholesterol (<40mg/dl in men, <50 mg/dl in women) or currently taking medication (Rx) High blood pressure (≥130 mmHg systolic or ≥85mmHg diastolic) or currently taking medication (Rx) Elevated fasting glucose (≥100 mg/dl)

Subject may participate if on the following drugs:

Diuretics, ace-inhibitors and ARBs for treatment of hypertension
Statins

Exclusion Criteria:

Morbidly obese patients (BMI >45 kg/m2) and overweight/lean patients (BMI <30 kg/m2).
Subjects who have not been weight stable (>2kg weight change in past 3 months).
Currently participating in a regular exercise training program ( >30 min. of physical activity per day, >2 days/week)
Medication or food supplement that is known to affect insulin sensitivity or endothelial function (TZDs, sulfonylureas, biguanides, alpha-glucosidase inhibitors, phosphodiesterase inhibitors, beta-blockers, alpha-blockers, fibrates, glucocorticoids, fish oil, allopurinol)
Subjects with abnormal estimated glomerular filtration rate (eGFR).
Hypertriglyceridemic (>400 mg/dl) subjects.
Hypertensive (>160/100 mmHg)
Subjects taking vasoactive medications also known to affect heart rate and rhythm (i.e. Ca++ 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.
Smoking presently or in the past 1 year.
HbA1c ≥ 6.5
Subjects currently taking Metformin or any active weight suppression medication (e.g. phentermine, orlistat, lorcaserin, naltrexone-bupropion in combination, liraglutide, benzphetamine, diethylpropion, phendimetrazine)
Pregnant (as evidenced by positive pregnancy test) or breastfeeding
Subjects with contraindications to participation in an exercise program
Known hypersensitivity to perflutren (contained in Definity)

Sites / Locations

University of VirginiaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Control

Metabolic Syndrome

Arm Description

Subjects with simple obesity will complete 2 different testing conditions in a counterbalanced order with at least one week between conditions. 10-12 hrs post test condition the subject will report for a Euglycemic-Hyperinsulinemic clamp study, where Flow Mediated Dilation (FMD) and Contrast Enhanced Ultrasound (CEU) will be performed.

Subjects with metabolic syndrome will complete 2 different testing conditions in a counterbalanced order with at least one week between conditions. 10-12 hrs post test condition the subject will report for a Euglycemic-Hyperinsulinemic clamp study, where Flow Mediated Dilation (FMD) and Contrast Enhanced Ultrasound (CEU) will be performed.

Outcomes

Primary Outcome Measures

Effect of single bout of exercise on FMD

Flow Mediated Dilation (FMD) as a percentage

Effect of single bout of exercise on CEU

Contrast Enhanced Ultrasound (CEU) as a percentage

Comparison of insulin stimulated FMD response

Flow mediated dilation as a percentage of fasting values

Comparison of insulin stimulated CEU response

Contrast Enhanced Ultrasound (CEU) as a percentage of fasting values

Secondary Outcome Measures

Systemic Arterial stiffness

Augmentation Index as a percentage

Central Arterial Stiffness

Pulse wave velocity in m/s

Metabolic Flexibility

Respiratory gases in fasted and insulin-stimulated states in arbitrary units

Fasting glucose

Comparison of glucose collected at baseline in mg/dl

Fasting insulin

Comparison of insulin collected at baseline in uU/ml

Free Fatty Acids

Comparison of free fatty acids collected at baseline in mEq/L

Adiponectin

Comparison of inflammatory in ng/ml

Full Information

NCT ID

NCT03894527

First Posted

March 5, 2019

Last Updated

March 26, 2019

Sponsor

University of Virginia

Collaborators

American College of Sports Medicine

1. Study Identification

Unique Protocol Identification Number

NCT03894527

Brief Title

Impact of Acute Exercise on Vascular Insulin Sensitivity in Metabolic Syndrome

Official Title

Impact of Acute Exercise on Vascular Insulin Sensitivity in Metabolic Syndrome

Study Type

Interventional

2. Study Status

Record Verification Date

March 2019

Overall Recruitment Status

Unknown status

Study Start Date

February 18, 2019 (Actual)

Primary Completion Date

September 30, 2019 (Anticipated)

Study Completion Date

January 31, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Virginia

Collaborators

American College of Sports Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

Obesity is an independent risk factor for type 2 diabetes and cardiovascular disease. The increased prevalence of obesity worldwide is a major concern among the scientific and medical communities. Insulin resistance is a common factor associated with obesity, metabolic syndrome, hypertension, and type 2 diabetes. Individuals affected by these conditions often experience endothelial dysfunction as well. Insulin resistance provides a key link between metabolic syndrome risk factors and vascular disease. Development of strategies aimed at preventing vascular dysfunction and future disease caused by metabolic disturbances is needed. Although the relationship between obesity and various diseases is well known, the acute effects of insulin on vascular function in obese individuals have yet to be fully determined. Additionally, the effects of acute exercise on insulin-stimulated endothelial function are unknown. Exercise may be an effective and potent treatment that protects against endothelial dysfunction, insulin resistance, and future cardiometabolic disease commonly present with obesity. However, less attention has been placed on vascular insulin sensitivity. The purpose of this study is to test the hypothesis that a single bout of exercise increases insulin-stimulated blood flow at the macro- and micro-vasculature level in obese individuals with metabolic syndrome to similar levels as healthy obese control. Our laboratory has available non-invasive methods to quantify vascular function and the gold-standard technique for assessing insulin sensitivity (euglycemic-hyperinsulinemic clamp). The investigators will assess vascular function (flow-mediated dilation, post-ischemic flow velocity and contrast-enhanced ultrasound) as well as arterial stiffness (augmentation index and pulse wave velocity) before and at the end of the clamp protocol performed the morning following a bout of exercise and a control (no-exercise) condition in 1) metabolic syndrome and 2) obese adults. If our hypothesis is sustained, it will suggest that a key role of the vasculature exists in regulating insulin following exercise and will provide insight into the link between the vasculature, obesity, metabolic syndrome and cardiovascular disease and may confer decreased risk for cardiometabolic disease.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metabolic Syndrome, Obesity

Keywords

Acute Exercise, Endothelial Function, Simple Obesity, Metabolic Syndrome

7. Study Design

Primary Purpose

Prevention

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

16 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Control

Arm Type

Active Comparator

Arm Description

Arm Title

Metabolic Syndrome

Arm Type

Active Comparator

Arm Description

Intervention Type

Behavioral

Intervention Name(s)

Single Bout of Exercise

Intervention Description

An exercise condition, which will be walking at a moderate intensity (~70% VO2peak). Time will vary based upon individual fitness levels to burn ~400kcals (estimated 0.5 - 1hr). Oxygen consumption will be measured during exercise via a metabolic cart to confirm energy expenditure. Participants will then rest following the exercise procedure for 20 minutes. Between 20 and 45 minutes following exercise, oxygen consumption will be measured to understand and capture excess post-exercise oxygen consumption (EPOC). Following this, participants will be provided with a standardize dinner and snack to consume in the AMP lab.

Intervention Type

Behavioral

Intervention Name(s)

Control Condition

Intervention Description

A control (no-exercise) condition. Participants will report to the AMP lab to rest for the same duration as the exercise bout and consume the standardized dinner and snack.

Primary Outcome Measure Information:

Title

Effect of single bout of exercise on FMD

Description

Flow Mediated Dilation (FMD) as a percentage

Time Frame

Baseline clamp study

Title

Effect of single bout of exercise on CEU

Description

Contrast Enhanced Ultrasound (CEU) as a percentage

Time Frame

Baseline Clamp Study

Title

Comparison of insulin stimulated FMD response

Description

Flow mediated dilation as a percentage of fasting values

Time Frame

Through study completion, up to about 4 weeks

Title

Comparison of insulin stimulated CEU response

Description

Contrast Enhanced Ultrasound (CEU) as a percentage of fasting values

Time Frame

Through study completion, up to about 4 weeks

Secondary Outcome Measure Information:

Title

Systemic Arterial stiffness

Description

Augmentation Index as a percentage

Time Frame

Through study completion, up to about 4 weeks

Title

Central Arterial Stiffness

Description

Pulse wave velocity in m/s

Time Frame

Through study completion, up to about 4 weeks

Title

Metabolic Flexibility

Description

Respiratory gases in fasted and insulin-stimulated states in arbitrary units

Time Frame

Through study completion, up to about 4 weeks

Title

Fasting glucose

Description

Comparison of glucose collected at baseline in mg/dl

Time Frame

Through study completion, up to about 4 weeks

Title

Fasting insulin

Description

Comparison of insulin collected at baseline in uU/ml

Time Frame

Through study completion, up to about 4 weeks

Title

Free Fatty Acids

Description

Comparison of free fatty acids collected at baseline in mEq/L

Time Frame

Through study completion, up to about 4 weeks

Title

Adiponectin

Description

Comparison of inflammatory in ng/ml

Time Frame

Through study completion, up to about 4 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

40 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Males and females, ages 40-70 years Never diagnosed with type 2 diabetes and/or cardiovascular disease Not currently engaged in > 60 min/wk of exercise Inclusion criteria specific to health obese vs. metabolic syndrome potential participants: Healthy Obese: (BMI ≥ 30 kg/m2 but ≤ 45 kg/m2) and no other metabolic syndrome risk factors, excluding waist circumference. Metabolic Syndrome: (BMI ≥ 30 kg/m2 but ≤ 45 kg/m2) and must meet at least 3 out 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 currently taking medication (Rx) Reduced HDL-cholesterol (<40mg/dl in men, <50 mg/dl in women) or currently taking medication (Rx) High blood pressure (≥130 mmHg systolic or ≥85mmHg diastolic) or currently taking medication (Rx) Elevated fasting glucose (≥100 mg/dl) Subject may participate if on the following drugs: Diuretics, ace-inhibitors and ARBs for treatment of hypertension Statins Exclusion Criteria: Morbidly obese patients (BMI >45 kg/m2) and overweight/lean patients (BMI <30 kg/m2). Subjects who have not been weight stable (>2kg weight change in past 3 months). Currently participating in a regular exercise training program ( >30 min. of physical activity per day, >2 days/week) Medication or food supplement that is known to affect insulin sensitivity or endothelial function (TZDs, sulfonylureas, biguanides, alpha-glucosidase inhibitors, phosphodiesterase inhibitors, beta-blockers, alpha-blockers, fibrates, glucocorticoids, fish oil, allopurinol) Subjects with abnormal estimated glomerular filtration rate (eGFR). Hypertriglyceridemic (>400 mg/dl) subjects. Hypertensive (>160/100 mmHg) Subjects taking vasoactive medications also known to affect heart rate and rhythm (i.e. Ca++ 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. Smoking presently or in the past 1 year. HbA1c ≥ 6.5 Subjects currently taking Metformin or any active weight suppression medication (e.g. phentermine, orlistat, lorcaserin, naltrexone-bupropion in combination, liraglutide, benzphetamine, diethylpropion, phendimetrazine) Pregnant (as evidenced by positive pregnancy test) or breastfeeding Subjects with contraindications to participation in an exercise program Known hypersensitivity to perflutren (contained in Definity)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Emily Heiston, M.Ed.

Phone

434-243-8677

emh5bh@virginia.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Steve Malin, PhD

Organizational Affiliation

University of Virginia

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Virginia

City

Charlottesville

State/Province

Virginia

ZIP/Postal Code

22904

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Emily Heiston, M.Ed.

Phone

434-243-8677

emh5bh@virginia.edu

First Name & Middle Initial & Last Name & Degree

Stephanie Miller, M.Ed.

Phone

434-243-8677

slm4ps@virginia.edu

12. IPD Sharing Statement

Plan to Share IPD

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Impact of Acute Exercise on Vascular Insulin Sensitivity in Metabolic Syndrome

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