Therapeutic Strategies for Microvascular Dysfunction in Type 1 Diabetes

• Status: Not yet recruiting
• Trial end date: 2027-06-01
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Virginia
• Treatments: Dulaglutide

Criteria

Inclusion criteria:

• History of type 1 diabetes, duration > 5 years

• Age 18-40 years

• HbA1c < 8.5%

• BMI 19-27 kg/m2

• Using insulin for diabetes treatment only (multiple daily injections or insulin pump with or without sensor augmentation)

• On stable regimen of non-diabetic medications for the last 6 months

• All screening labs within normal limits or not clinically significant

• C-peptide <0.6 ng/ml

• Performing less than 150 minutes of moderate intensity physical activity or less than 70 minutes of high intensity physical activity per week (i.e. achieving less physical activity than recommended by the American Diabetes Association)

Exclusion criteria:

• Pregnancy or currently breastfeeding

• Smoking history within 6 months

• History of microvascular (microalbuminuria, retinopathy, neuropathy) or macrovascular diabetes complications (coronary artery disease, stroke, peripheral vascular disease) as well as clinically significant cardiac arrhythmias or conduction disorders

• Taking vasoactive medications (i.e. calcium channel blockers, angiotensin-converting enzyme or renin inhibitors, angiotensin-receptor blockers, nitrates, alpha-blockers).

• Known hypersensitivity to perflutren (contained in Definity© contrast)

• Screening O2 saturation <90%

• Musculoskeletal condition preventing participation in exercise testing or exercise training

• Acute or unstable disease other than T1D

• Hypoglycemia unawareness (based on Clarke's questionnaire)

• History of gastroparesis, severe gastroesophageal reflux, pancreatitis, personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2

• Anemia (hemoglobin <12 g/dL in women, hemoglobin <13 g/dL in men), eosinophilia (absolute eosinophil count >500 cells/microliter) leukopenia (total white blood cells <4,000 cells/microliter)

• Diabetic ketoacidosis (DKA) on presentation to screening visits or study admission days

• Hospital admission for DKA within 1 year