NCT05478707

Therapeutic Strategies for Microvascular Dysfunction in Type 1 Diabetes

• Status: Suspended
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 47 (estimated)
• Sponsor: University of Virginia · Academic / Other
• Sex: All
• Age: 18 Years – 40 Years
• Healthy volunteers: Not accepted

Summary

The investigators will test the hypothesis that, in adults with type 1 diabetes (T1D), glucagon-like peptide-1 receptor agonism (GLP-1RA, i.e. dulaglutide) enhances insulin-mediated skeletal muscle microvascular perfusion via attenuating endothelial oxidative stress and thereby improving endothelial function.

Detailed description

In this study, 47 (n=32 needed to complete) adult participants with type 1 diabetes will be randomized (1:1) to 14-weeks of one of 2 interventions: 1) dulaglutide, 2) placebo. Participants will undergo two study admissions at baseline and 14 weeks. Prior to each admission, participants will wear a continuous glucose monitor (Dexcom G6 Professional) for 10 days to assess glycemic variability (GV). Prior to admissions, they will undergo cardiorespiratory fitness testing. On study admission days, participants will undergo an antecubital vein endothelial cell biopsy prior to commencing vascular testing. From the harvested endothelial cells, the investigators will quantify endothelial cell reactive oxygen species (ROS) and gene expression relevant to insulin-mediated endothelial function. Vascular testing will include contrast enhanced ultrasound of quadriceps muscle to determine microvascular blood volume (MBV). The investigators will also measure brachial artery flow mediated dilation (FMD). Quadriceps skeletal muscle oxygenation (HHb) will also be measured. These vascular and muscle oxygenation measurements will be conducted before and after a 120-minute euglycemic insulin clamp which will measure insulin sensitivity based on glucose infusion rate (GIR). This randomized, placebo-controlled study will assess whether GLP-1 receptor agonism with dulaglutide or exercise training improves insulin-mediated skeletal muscle microvascular perfusion. The investigators will assess for predictive relationships between microvascular perfusion and cardiorespiratory fitness (VO2max), insulin sensitivity (GIR), endothelial reactive oxygen species (ROS), and glycemic variability (GV).

Conditions

• Diabetes Mellitus, Type 1
• Endothelial Dysfunction

Interventions

Type	Name	Description
DRUG	Dulaglutide	GLP1-RA
DRUG	Placebo	Saline placebo

Timeline

• Start date: 2023-10-05
• Primary completion: 2028-06-30
• Completion: 2028-07-30
• First posted: 2022-07-28
• Last updated: 2026-04-09

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study