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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Liraglutide
  24 weeks of Liraglutide
• Другое Exercise training
  24 weeks of Exercise training
• Препарат Liraglutide + Exercise training
  24 weeks of Liraglutide + Exercise training

Первичные конечные точки

• Microvascular Blood Volume - change from baseline [Срок оценки: 24 weeks]

Вторичные конечные точки (5)

• Augmentation Index - change from baseline [Срок оценки: 24 weeks]
• Flow Mediated Dilation [Срок оценки: 24 weeks]
• Pulse Wave Velocity [Срок оценки: 24 weeks]
• Post Ischemic Flow Velocity - change from baseline [Срок оценки: 24weeks]
• Insulin Sensitivity - change from baseline [Срок оценки: 24 weeks]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Факторный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of Virginia — Charlottesville

Публикации

• 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/S0140-67 PMID 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. PMID 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. PMID 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. PMID 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. PMID 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. PMID 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. PMID 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. PMID 21047922

Идентификаторы

NCT: NCT04575844 · 200065 · R01DK125330

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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