Exercise and Carotid Artery Function in Metabolic Syndrome

Identifying Sex-specific Carotid Endothelial Dysfunction in Young Adults With Metabolic Syndrome

The purpose of this study is to determine 1) if young adults with metabolic syndrome display endothelial dysfunction of the internal carotid artery in a sex-specific fashion and 2) if this endothelial dysfunction can be acutely improved with a single bout of exercise. This will be achieved by testing internal carotid artery function before and after a 30-minute bout of moderate intensity exercise. 48 young adults with and without metabolic syndrome will be enrolled and will be on study for approximately 5.5 hours over 4 study visits.

Study Overview

• Status: Recruiting
• Conditions: Metabolic Syndrome
• Intervention / Treatment: Behavioral: exercise; Diagnostic test: Diagnostics; Other: Inhaled CO2-mixed air

Detailed Description

The goal of this project is to determine if young MetSyn patients exhibit carotid endothelial dysfunction (ED) in a sex-specific manner and if exercise can acutely restore internal carotid artery (ICA) function.

The investigators will test this by first quantifying ICA endothelial function using an inhaled gas stressor (CO2) to acutely increase ICA shear rate (SR) and measuring the vascular responsiveness to this increased SR. Carotid endothelial function has never been tested in this way in patients with MetSyn before. Then, a 30 min bout of cycling exercise will be performed followed by the same gas stressor test to determine if ICA endothelial function can be acutely improved in MetSyn.

The aims and hypotheses are to:

• Aim 1: Determine if young adults with MetSyn exhibit carotid ED compared to healthy adults. Hypothesis: carotid ED will be present in young adults with MetSyn.
• Aim 2: Determine if sex differences exist in carotid endothelial function in MetSyn. Hypothesis: MetSyn will result in greater declines in carotid endothelial function in females.
• Aim 3: Determine if exercise yields an acute benefit on carotid endothelial function in young adults with MetSyn. Hypothesis: young adults with MetSyn will receive a greater increase in carotid endothelial function from a single bout of exercise than healthy adults.

• Study Type: Observational
• Enrollment (Estimated): 48

Contacts and Locations

• Study Contact: Name: Shawn Bolin, MS; Phone Number: 608-263-6308; Email: sbolin@wisc.edu
• Study Contact Backup: Name: Logan Heenan, BS; Phone Number: 608-263-6308; Email: lheenan@wisc.edu

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Recruiting
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Young adult male and female participants with metabolic syndrome and age matched healthy male and female participants.

Description

Inclusion Criteria (MetSyn cohort):

• Waist circumference greater than 102 cm (males) or 82 cm (females)
• Triglycerides over 150 mg/dL
• HDL cholesterol less than 40 mg/dL (males) or 50 mg/dL (females)
• Blood pressure ≥130/85 mmHg
• Fasting plasma glucose over 110 mg/dL

Inclusion Criteria (Healthy cohort):

- meet age criteria

Exclusion Criteria:

• Current smoker, defined as more than 5 cigarettes over past 30 days

• Current diagnosis or history of:

  • peripheral vascular disease
  • hepatic disease
  • renal disease
  • lung disease
  • gastrointestinal disorders/bleeding
  • hematologic disease
  • stroke
  • myocardial infarction
  • coronary heart disease
  • congestive heart failure
  • heart surgery
  • sleep apnea
  • autoimmune diseases
  • traumatic brain injury, concussion, stroke, or seizures
  • Asthma
  • Polycystic ovarian syndrome
• Type II diabetes
• Currently pregnant or breastfeeding
• Current musculoskeletal injury Medication use known to influence cardiovascular function, other than oral contraceptives
• Hormonal contraceptive use, such as intrauterine device or hormonal implant use
• Participants with ICAs unsuitable for imaging, as assessed during the screening visit via doppler ultrasonography

Exclusion Criteria (healthy controls only):

• BMI greater than 25 kg/m2
• Blood pressure over 125/80 mmHg
• Meeting any MetSyn criteria listed for MetSyn cohort

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Young Male adults with MetSyn; Graded Exercise Trial to determine cardiorespiratory fitness; Submaximal Exercise Trial to assess primary aims of the study (ICA function will be assessed using the cSMD test); Sitting Control Trial (ICA function will be assessed using the cSMD test)	Behavioral: exercise; 30 minute bout of cycling; Diagnostic test: Diagnostics; Doppler Ultrasound used to non-invasively assess the diameter and blood flow going into an artery, the ICA in this study.; Indirect calorimeter in tandem with semi-recumbent bike used to assess O2 consumption; heart rate monitor; Other: Inhaled CO2-mixed air; Three gases of different composition are used to ensure that the proper PETCO2 administration desired for this study occurs in tandem with keeping inspired O2 content constant. This is achieved by used a 5% O2, 95% CO2 tank, a 5% O2, 95% N2 tank, and a 100% O2 tank. In tandem, the use of these three tanks allows for precise control of PETCO2 without a change in inspired O2.
Young Female adults with MetSyn; Graded Exercise Trial to determine cardiorespiratory fitness; Submaximal Exercise Trial to assess primary aims of the study (ICA function will be assessed using the cSMD test); Sitting Control Trial (ICA function will be assessed using the cSMD test)	Behavioral: exercise; 30 minute bout of cycling; Diagnostic test: Diagnostics; Doppler Ultrasound used to non-invasively assess the diameter and blood flow going into an artery, the ICA in this study.; Indirect calorimeter in tandem with semi-recumbent bike used to assess O2 consumption; heart rate monitor; Other: Inhaled CO2-mixed air; Three gases of different composition are used to ensure that the proper PETCO2 administration desired for this study occurs in tandem with keeping inspired O2 content constant. This is achieved by used a 5% O2, 95% CO2 tank, a 5% O2, 95% N2 tank, and a 100% O2 tank. In tandem, the use of these three tanks allows for precise control of PETCO2 without a change in inspired O2.
Young Male Healthy Controls; Graded Exercise Trial to determine cardiorespiratory fitness; Submaximal Exercise Trial to assess primary aims of the study (ICA function will be assessed using the cSMD test); Sitting Control Trial (ICA function will be assessed using the cSMD test)	Behavioral: exercise; 30 minute bout of cycling; Diagnostic test: Diagnostics; Doppler Ultrasound used to non-invasively assess the diameter and blood flow going into an artery, the ICA in this study.; Indirect calorimeter in tandem with semi-recumbent bike used to assess O2 consumption; heart rate monitor; Other: Inhaled CO2-mixed air; Three gases of different composition are used to ensure that the proper PETCO2 administration desired for this study occurs in tandem with keeping inspired O2 content constant. This is achieved by used a 5% O2, 95% CO2 tank, a 5% O2, 95% N2 tank, and a 100% O2 tank. In tandem, the use of these three tanks allows for precise control of PETCO2 without a change in inspired O2.
Young Female Healthy Controls; Graded Exercise Trial to determine cardiorespiratory fitness; Submaximal Exercise Trial to assess primary aims of the study (ICA function will be assessed using the cSMD test); Sitting Control Trial (ICA function will be assessed using the cSMD test)	Behavioral: exercise; 30 minute bout of cycling; Diagnostic test: Diagnostics; Doppler Ultrasound used to non-invasively assess the diameter and blood flow going into an artery, the ICA in this study.; Indirect calorimeter in tandem with semi-recumbent bike used to assess O2 consumption; heart rate monitor; Other: Inhaled CO2-mixed air; Three gases of different composition are used to ensure that the proper PETCO2 administration desired for this study occurs in tandem with keeping inspired O2 content constant. This is achieved by used a 5% O2, 95% CO2 tank, a 5% O2, 95% N2 tank, and a 100% O2 tank. In tandem, the use of these three tanks allows for precise control of PETCO2 without a change in inspired O2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aim 1: Baseline ICA cSMD measures assessed by MetSyn versus healthy controls	Internal carotid artery cerebral shear-mediated dilation (cSMD) is measured by doppler ultrasound and reported in percentage increase in diameter. A resting baseline period for 5 minutes breathing room air followed by 30 seconds of breathing CO2-mixed air at +9 mmHg PETCO2 used to evoke an increase in blood flow to the ICA.	baseline
Aim 2: Baseline ICA cSMD measures assessed by MetSyn versus sex	Internal carotid artery cerebral shear-mediated dilation is measured by doppler ultrasound and reported in percentage increase in diameter. A resting baseline period for 5 minutes breathing room air followed by 30 seconds of breathing CO2-mixed air at +9 mmHg PETCO2 used to evoke an increase in blood flow to the ICA.	baseline
Aim 3: Post-exercise cSMD response by MetSyn versus healthy controls	Internal carotid artery cerebral shear-mediated dilation is measured by doppler ultrasound and reported in percentage increase in diameter. 30 minutes of exercise on a cycle ergometer will be performed at 80% of the ventilatory threshold determined during the graded exercise test.	measured during exercise and 10 and 60 minutes post-exercise

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aim 3: Duration of Response to Exercise	Duration of post-exercise improvements will be investigated by testing ICA cSMD 10 min and 60 min post-exercise. 30 minutes of exercise on a cycle ergometer will be performed at 80% of the ventilatory threshold determined during the graded exercise test. For the duration of the exercise, indirect calorimetry will be used to assess VO2 to confirm the target workload of 80% of the ventilatory threshold. During this 30 minutes of exercise, ICA diameter and velocity will be measured using ultrasonography every 5 minutes for a 2-minute period.	measured during exercise and 10 and 60 minutes post-exercise

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Investigators: Principal Investigator: William Schrage, PhD, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: February 17, 2026
• First Submitted That Met QC Criteria: February 17, 2026
• First Posted (Actual): February 24, 2026

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 24, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: exercise
• Additional Relevant MeSH Terms: Metabolic Diseases; Glucose Metabolism Disorders; Insulin Resistance; Hyperinsulinism; Behavior; Nutritional and Metabolic Diseases; Metabolic Syndrome; Motor Activity; Health Services Administration; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Patient Care Management; Point-of-Care Testing; Point-of-Care Systems; Exercise; Rapid Diagnostic Tests
• Other Study ID Numbers: 2025-0017; A176000 (Other Identifier: UW Madison); 25PRE1410388 (Other Grant/Funding Number: American Heart Association); Protocol Version 2/21/26 (Other Identifier: UW Madison)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No