Therapeutic Strategies for Microvascular Dysfunction in Type 1 Diabetes (MCD-1)

August 10, 2026 updated by: Kaitlin Love, AdventHealth Translational Research Institute
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Estimated)

47

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 40 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion criteria:

  • 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 - English or Spanish speaking

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
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Saline subcutaneous injection, volume matched to dulaglutide, i.e. 0.5 mL weekly for 14 weeks
Drug: Placebo
Saline placebo
Active Comparator: Dulaglutide
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
GLP1-RA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Microvascular blood volume (MBV)
Time Frame: At baseline and after 14 weeks of treatment.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Brachial artery flow mediated dilation (FMD)
Time Frame: At baseline and after 14 weeks of treatment
Post-occlusive percent (%) change in diameter. A measure of conduit artery nitric oxide-dependent endothelial function.
At baseline and after 14 weeks of treatment
Glucose infusion rate (GIR)
Time Frame: At baseline and after 14 weeks of treatment
Mean GIR over the final 30 minutes of euglycemic insulin clamp; a measure of insulin sensitivity
At baseline and after 14 weeks of treatment
Cardiorespiratory fitness, maximum consumption of oxygen (VO2max)
Time Frame: At baseline and after 14 weeks of treatment
Assessed by cycle ergometer exercise testing.
At baseline and after 14 weeks of treatment
Skeletal muscle oxygenation, deoxyhemoglobin (HHb)
Time Frame: At baseline and after 14 weeks of treatment. Measured before and after insulin clamp.
Assessed by frequency domain multi-distance near-infrared spectroscopy (NIRS) monitor at the quadriceps muscle
At baseline and after 14 weeks of treatment. Measured before and after insulin clamp.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AdventHealth Translational Research Institute

Investigators

  • Principal Investigator: Kaitlin Love, MD, Site Principal Investigator

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 5, 2023

Primary Completion (Estimated)

June 30, 2028

Study Completion (Estimated)

July 30, 2028

Study Registration Dates

First Submitted

July 25, 2022

First Submitted That Met QC Criteria

July 25, 2022

First Posted (Actual)

July 28, 2022

Study Record Updates

Last Update Posted (Actual)

August 12, 2026

Last Update Submitted That Met QC Criteria

August 10, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2351846

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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