Therapeutic Strategies for Microvascular Dysfunction in Type 1 Diabetes

NCT05478707 | Suspended Phase 2 DMC FDA Drug

• 1 other identifier: 210198
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Diabetes Mellitus, Type 1; Endothelial Dysfunction

Keywords

microvessels; oxidative stress; Dulaglutide; Glucagon-like peptide-1; Exercise therapy

Outcome Measures

Primary Outcomes (1)

• Microvascular blood volume (MBV)

  Insulin mediated change in muscle microvascular blood volume (MBV). A measure of microvascular nitric oxide dependent endothelial function

  At baseline and after 14 weeks of treatment.

Secondary Outcomes (4)

• Brachial artery flow mediated dilation (FMD)

  At baseline and after 14 weeks of treatment

• Glucose infusion rate (GIR)

  At baseline and after 14 weeks of treatment

• Cardiorespiratory fitness, maximum consumption of oxygen (VO2max)

  At baseline and after 14 weeks of treatment

• Skeletal muscle oxygenation, deoxyhemoglobin (HHb)

  At baseline and after 14 weeks of treatment. Measured before and after insulin clamp.

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Saline subcutaneous injection, volume matched to dulaglutide, i.e. 0.5 mL weekly for 14 weeks

Drug: Placebo

Dulaglutide

ACTIVE COMPARATOR

Dulaglutide (0.75 mg/0.5 mL weekly for 2 weeks, then 1.5 mg/0.5 mL weekly for 12 weeks) subcutaneous injection

Drug: Dulaglutide

Interventions

Dulaglutide DRUG

GLP1-RA

Dulaglutide

Placebo DRUG

Saline placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• History of type 1 diabetes, duration \> 5 years
• Age 18-40 years
• HbA1c \< 8.5%
• BMI 19-34.9 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Virginia: lead

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Related Publications (58)

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MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

dulaglutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Kaitlin Love, MD

  Associate Professor - Endocrinology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Participants randomized to dulaglutide or placebo and study personnel who analyze data and instruct patients regarding insulin adjustments will be blinded to treatment allocation.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 25, 2022
• First Posted: July 28, 2022
• Study Start: October 5, 2023
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): July 30, 2028
• Last Updated: April 9, 2026

Record last verified: 2026-04

Locations

US (1)