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Metabolic SyndromePhase 4ZQL008NCT04575844

Effects of Exercise and GLP-1 Agonism on Muscle Microvascular Perfusion and Insulin Action in Adults With Metabolic Syndrome

A Phase 4 study testing Liraglutide, Exercise training and Liraglutide + Exercise training in people with Metabolic Syndrome, run by University of Virginia at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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… Read more about this study

Who is it for?
Ages 21 to 60 yearsHealthy volunteers can take part
Conditions the study is for
Metabolic Syndrome
What is being tested?
Liraglutide, Exercise training and Liraglutide + Exercise training
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
1 siteUnited States
Study dates
1 Nov 2020to 30 Apr 2027
Phase
Phase 4
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 to 60 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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)
Show all 16Show fewer
  • 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

Who cannot join

  • 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
Show all 10Show fewer
  • 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Lee Hartline, MEd contact

434-924-5247

lmh9d@virginia.edu

Linda Jahn, MEd contact

434-924-1134

las6e@virginia.edu

United States1 site, 1 recruiting
  • University of Virginia

    Charlottesville, Virginia, 22906

    Zhenqi Liu, MD, 434-243-2603, zl3e@virginia.edu

    Eugene Barrett, MD, PhD, 434-924-1175, ejb8x@virginia.edu

    Recruiting

Other trials in United States

About this study

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.

Read the 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.

Being tested
Liraglutide, Exercise training, Liraglutide + Exercise training
Medical subject headings
Metabolic Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LiraglutideDrug

    24 weeks of Liraglutide

  • Exercise trainingOther

    24 weeks of Exercise training

  • Liraglutide + Exercise trainingDrug

    24 weeks of Liraglutide + Exercise training

Study groups in NCT04575844
Study groupRoleWhat they receive
Exercise AloneExperimental24 weeks of treatment
Receives: Other: Exercise training
Liraglutide AloneExperimental24 weeks of treatment
Receives: Drug: Liraglutide
Exercise + LiraglutideExperimental24 weeks f treatment
Receives: Drug: Liraglutide + Exercise training

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Microvascular Blood Volume - change from baseline

    measured at baseline and 24 weeks

    Measured: 24 weeks

Secondary outcomes (5)
  1. Augmentation Index - change from baseline

    measured at baseline and 24 weeks

    Measured: 24 weeks

  2. Flow Mediated Dilation

    measured at baseline and 24 weeks

    Measured: 24 weeks

  3. Pulse Wave Velocity

    measured at baseline and 24 weeks

    Measured: 24 weeks

  4. Post Ischemic Flow Velocity - change from baseline

    measured at baseline and 24 weeks

    Measured: 24weeks

  5. Insulin Sensitivity - change from baseline

    measured at baseline and 24 weeks

    Measured: 24 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Oct 2020
  2. Study start1 Nov 2020
  3. Primary completion30 Apr 2027 (estimated)
  4. Study completion30 Apr 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Factorial
Masking
None (open label)
Enrolment
80 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04575844
Sponsor's protocol ID
200065
Other IDs
R01DK125330
Acronym
ZQL008
Status last verified
May 2026
First submitted
27 Sep 2020
Last updated
6 May 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • le Roux CW, Astrup A, Fujioka K, Greenway F, Lau DCW, Van Gaal L, Ortiz RV, Wilding JPH, Skjoth TV, Manning LS, Pi-Sunyer X; SCALE Obesity Prediabetes NN8022-1839 Study Group. 3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial. Lancet. 2017 Apr 8;389(10077):1399-1409. doi: 10.1016/S0140-6736(17)30069-7. Epub 2017 Feb 23.

    PubMed 28237263
  • Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, Nissen SE, Pocock S, Poulter NR, Ravn LS, Steinberg WM, Stockner M, Zinman B, Bergenstal RM, Buse JB; LEADER Steering Committee; LEADER Trial Investigators. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2016 Jul 28;375(4):311-22. doi: 10.1056/NEJMoa1603827. Epub 2016 Jun 13.

    PubMed 27295427
  • Barrett EJ, Wang H, Upchurch CT, Liu Z. Insulin regulates its own delivery to skeletal muscle by feed-forward actions on the vasculature. Am J Physiol Endocrinol Metab. 2011 Aug;301(2):E252-63. doi: 10.1152/ajpendo.00186.2011. Epub 2011 May 24.

    PubMed 21610226
  • Vincent MA, Clerk LH, Lindner JR, Klibanov AL, Clark MG, Rattigan S, Barrett EJ. Microvascular recruitment is an early insulin effect that regulates skeletal muscle glucose uptake in vivo. Diabetes. 2004 Jun;53(6):1418-23. doi: 10.2337/diabetes.53.6.1418.

    PubMed 15161743
  • Eggleston EM, Jahn LA, Barrett EJ. Hyperinsulinemia rapidly increases human muscle microvascular perfusion but fails to increase muscle insulin clearance: evidence that a saturable process mediates muscle insulin uptake. Diabetes. 2007 Dec;56(12):2958-63. doi: 10.2337/db07-0670. Epub 2007 Aug 24.

    PubMed 17720897
  • Chai W, Wang W, Liu J, Barrett EJ, Carey RM, Cao W, Liu Z. Angiotensin II type 1 and type 2 receptors regulate basal skeletal muscle microvascular volume and glucose use. Hypertension. 2010 Feb;55(2):523-30. doi: 10.1161/HYPERTENSIONAHA.109.145409. Epub 2009 Dec 7.

    PubMed 19996061
  • Liu Z, Liu J, Jahn LA, Fowler DE, Barrett EJ. Infusing lipid raises plasma free fatty acids and induces insulin resistance in muscle microvasculature. J Clin Endocrinol Metab. 2009 Sep;94(9):3543-9. doi: 10.1210/jc.2009-0027. Epub 2009 Jun 30.

    PubMed 19567533
  • Liu J, Jahn LA, Fowler DE, Barrett EJ, Cao W, Liu Z. Free fatty acids induce insulin resistance in both cardiac and skeletal muscle microvasculature in humans. J Clin Endocrinol Metab. 2011 Feb;96(2):438-46. doi: 10.1210/jc.2010-1174. Epub 2010 Nov 3.

    PubMed 21047922
  • Vincent MA, Barrett EJ, Lindner JR, Clark MG, Rattigan S. Inhibiting NOS blocks microvascular recruitment and blunts muscle glucose uptake in response to insulin. Am J Physiol Endocrinol Metab. 2003 Jul;285(1):E123-9. doi: 10.1152/ajpendo.00021.2003.

    PubMed 12791603
  • Clerk LH, Vincent MA, Jahn LA, Liu Z, Lindner JR, Barrett EJ. Obesity blunts insulin-mediated microvascular recruitment in human forearm muscle. Diabetes. 2006 May;55(5):1436-42. doi: 10.2337/db05-1373.

    PubMed 16644702
  • Youd JM, Rattigan S, Clark MG. Acute impairment of insulin-mediated capillary recruitment and glucose uptake in rat skeletal muscle in vivo by TNF-alpha. Diabetes. 2000 Nov;49(11):1904-9. doi: 10.2337/diabetes.49.11.1904.

    PubMed 11078458
  • Liu Z. The vascular endothelium in diabetes and its potential as a therapeutic target. Rev Endocr Metab Disord. 2013 Mar;14(1):1-3. doi: 10.1007/s11154-013-9238-8. No abstract available.

    PubMed 23397463
  • Gavin TP, Stallings HW 3rd, Zwetsloot KA, Westerkamp LM, Ryan NA, Moore RA, Pofahl WE, Hickner RC. Lower capillary density but no difference in VEGF expression in obese vs. lean young skeletal muscle in humans. J Appl Physiol (1985). 2005 Jan;98(1):315-21. doi: 10.1152/japplphysiol.00353.2004. Epub 2004 Aug 6.

    PubMed 15298982
  • Lillioja S, Young AA, Culter CL, Ivy JL, Abbott WG, Zawadzki JK, Yki-Jarvinen H, Christin L, Secomb TW, Bogardus C. Skeletal muscle capillary density and fiber type are possible determinants of in vivo insulin resistance in man. J Clin Invest. 1987 Aug;80(2):415-24. doi: 10.1172/JCI113088.

    PubMed 3301899
  • Solomon TP, Haus JM, Li Y, Kirwan JP. Progressive hyperglycemia across the glucose tolerance continuum in older obese adults is related to skeletal muscle capillarization and nitric oxide bioavailability. J Clin Endocrinol Metab. 2011 May;96(5):1377-84. doi: 10.1210/jc.2010-2069. Epub 2011 Feb 2.

    PubMed 21289242

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Liraglutide, Exercise training and Liraglutide + Exercise training in people with Metabolic Syndrome, run by University of Virginia at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 6 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Lee Hartline, MEd (434-924-5247, lmh9d@virginia.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Microvascular Blood Volume - change from baseline (time frame: 24 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04575844, which also lists 38 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2026.

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