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Clinical Trial NCT05478707 (KML002) for Diabetes Mellitus, Type 1, Endothelial Dysfunction is recruiting. See the Trial Radar Card View and AI discovery tools for all the details. Or ask anything here.
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Therapeutic Strategies for Microvascular Dysfunction in Type 1 Diabetes (KML002)

Recruiting
Clinical Trial NCT05478707 (KML002) is designed to study Basic Science for Diabetes Mellitus, Type 1, Endothelial Dysfunction. It is a Phase 2 interventional trial that is recruiting, having started on 5 October 2023, with plans to enroll 64 participants. Led by University of Virginia, it is expected to complete by 30 June 2027. The latest data from ClinicalTrials.gov was last updated on 12 November 2024.
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) and exercise training each enhance insulin-mediated skeletal muscle microvascular perfusion via attenuating endothelial oxidative stress and thereby improving endothelial function.
Detailed Description
In this study, 64 (n=48 needed to complete) adult participants with type 1 diabetes will be randomized (1:1:1) to 14-weeks of one of 3 interventions: 1) dulaglutide, 2) placebo, or 3) exercise training.

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 protein 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).

Official Title

Therapeutic Strategies for Microvascular Dysfunction in Type 1 Diabetes

Conditions
Diabetes Mellitus, TYPE 1Endothelial Dysfunction
Publications
Scientific articles and research papers published about this clinical trial:
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Other Study IDs
  • KML002
  • 210198
NCT ID Number
Start Date (Actual)
2023-10-05
Last Update Posted
2024-11-12
Completion Date (Estimated)
2027-06-30
Enrollment (Estimated)
64
Study Type
Interventional
PHASE
Phase 2
Status
Recruiting
Keywords
microvessels
oxidative stress
Dulaglutide
Glucagon-like peptide-1
Exercise therapy
Primary Purpose
Basic Science
Design Allocation
Randomized
Interventional Model
Parallel
Masking
Triple
Arms / Interventions
Participant Group/ArmIntervention/Treatment
Placebo ComparatorPlacebo
Saline subcutaneous injection, volume matched to dulaglutide, i.e. 0.5 mL weekly for 14 weeks
Placebo
Saline placebo
Active ComparatorDulaglutide
Dulaglutide (0.75 mg/0.5 mL weekly for 2 weeks, then 1.5 mg/0.5 mL weekly for 12 weeks) subcutaneous injection
Dulaglutide
GLP1-RA
Active ComparatorExercise training
Supervised high intensity interval training on a stationary bicycle will be conducted 3 days per week for 14 weeks. Participants will warm up at low intensity for 3 min then repeat 1-min bouts of 100% peak power output followed by 1-min recovery at 50 W. Training will start with 6 intervals per session, increasing by 2 intervals every 2 weeks. Sessions will end with a 10-min cool-down.
Exercise Training
supervised high intensity interval training
Primary Outcome Measures
Outcome MeasureMeasure DescriptionTime Frame
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 Outcome Measures
Outcome MeasureMeasure DescriptionTime Frame
Brachial artery flow mediated dilation (FMD)
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)
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)
Assessed by cycle ergometer exercise testing.
At baseline and after 14 weeks of treatment
Skeletal muscle oxygenation, deoxyhemoglobin (HHb)
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.
Eligibility Criteria

Eligible Ages
Adult
Minimum Age
18 Years
Eligible Sexes
All
  • 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

  • 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
University of Virginia logoUniversity of Virginia297 active trials to explore
Study Responsible Party
Kaitlin Love, MD, Principal Investigator, Principal Investigator, University of Virginia
Study Central Contact
Contact: Kaitlin Love, MD, 434-924-9651, [email protected]
Contact: Lee Hartline, MEd, [email protected]
1 Study Locations in 1 Countries

Virginia

University of Virginia, Charlottesville, Virginia, 22908, United States
Kaitlin Love, MD, Contact, [email protected]
Recruiting