Clinical trial NCT04575844: Effects of Exercise and GLP-1 Agonism on Muscle Microvascular Perfusion and Insulin Action in Adults With Metabolic Syndrome
Official title: Effects of Exercise and GLP-1 Agonism on Muscle Microvascular Perfusion and Insulin Action in Adults With Metabolic Syndrome
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Metabolic Syndrome
Lead sponsor: University of Virginia
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2020-10-05
Enrollment: 80
Sex: ALL
Minimum age (years): 21
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to examine whether exercise training alone, liraglutide treatment alone or exercise training plus liraglutide treatment increases cardiac and skeletal muscle microvascular blood volume, improves vascular function of the conduit vessels, and enhances insulin's metabolic action in humans with Metabolic Syndrome. Subjects will be randomized to one of the 4 groups: control, exercise training, liraglutide treatment, and exercise + liraglutide. They will be studied at the baseline and then after 24 weeks of intervention.

Detailed description: Our hypothesis is that sustained activation of the GLP-1 receptor with Liraglutide and exercise training each will enhance microvascular insulin responses and angiogenesis in both cardiac and skeletal muscle to increase muscle insulin delivery and action and the combination of both is more effective than either alone in adults with metabolic syndrome.

Eligibility criteria: Inclusion Criteria:

* Male or female ≥21 and ≤60 years old.
* Body mass index \>25 and ≤35 kg/m2 and is weight stable (\<5 kg weight change in the past 6 months). BMI is limited to ≤35 kg/m2 for easier vascular access and cardiac imaging.
* Meet 3 of 5 National Cholesterol Education Program Adult Treatment Panel III Metabolic Syndrome criteria:

  * Increased waist circumference (≥102 cm in men; ≥88 cm in women)
  * Elevated triglycerides (≥150 mg/dl)
  * Reduced HDL-cholesterol (\<40mg/dl in men, \<50 mg/dl in women)
  * High blood pressure (≥130 mmHg systolic or ≥85mmHg diastolic)
  * Elevated fasting glucose (≥100 mg/dl)
  * Subject may participate if on the following drugs, provided the drug doses have been stable for at least 3 months.
  * Ace inhibitor
  * ARB
  * HMG CoA reductase inhibitor
  * Beta blocker
  * Calcium channel blockers
  * Alpha-adrenergic antagonist
  * Statin

Exclusion Criteria:

* A diagnosis of any type of diabetes or history of diabetes medication use
* Recently active (\>20 min of moderate/high intensity exercise, 2 times/week)
* Subjects who are smokers or who have quit smoking \<5 years
* Subjects with hypertriglyceridemia (\>400 mg/dl) or hypercholesterolemia (\>260 mg/dl)
* Subjects with BP\>160/90
* Subjects with a history of significant metabolic, cardiac, cerebrovascular, hematological, pulmonary, gastrointestinal, liver, renal, or endocrine disease or malignancy
* Pregnant (as evidenced by positive pregnancy test) or nursing women
* Subjects with contraindications to participation in an exercise training program
* Allergic to perflutren
* A prior use of Liraglutide

Primary outcomes:
measure: Microvascular Blood Volume - change from baseline
timeFrame: 24 weeks
Secondary outcomes:
measure: Augmentation Index - change from baseline
timeFrame: 24 weeks
measure: Flow Mediated Dilation
timeFrame: 24 weeks
measure: Pulse Wave Velocity
timeFrame: 24 weeks
measure: Post Ischemic Flow Velocity - change from baseline
timeFrame: 24weeks
measure: Insulin Sensitivity - change from baseline
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
affiliation: Division of Endocrinology and Metabolism, University of Virginia
name: Zhenqi Liu, MD
role: PRINCIPAL_INVESTIGATOR
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