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KML001: Effect of GLP-1 on Microvascular Insulin Responses in Type 1 Diabetes

Sponsor
University of Virginia (Other)
Overall Status
Withdrawn
CT.gov ID
NCT04133922
Collaborator
American Diabetes Association (Other), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
0
Enrollment
1
Location
3
Arms
59.6
Anticipated Duration (Months)
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

GLP-1 increases skeletal and cardiac microvascular perfusion and improves insulin's microvascular responses in human subjects with T1DM, leading to improved metabolic insulin responses, endothelial function, and increased muscle oxygenation

Condition or Disease Intervention/Treatment Phase
Early Phase 1

Detailed Description

The proposed study will determine the effect of GLP-1 infusion on microvascular perfusion and microvascular insulin responses in both skeletal and cardiac muscle microvasculature in humans with T1DM. The investigators will study 20 participants with T1DM using a state-of-the-art technology, contrast enhanced ultrasound (CEU), to assess whether GLP-1 augments skeletal and cardiac microvascular blood flow (MBF) as a representation of microvascular perfusion, flow-mediated dilation (FMD) as a measurement of endothelial function, and augmentation index (AI) and pulse wave velocity (PWV) as surrogates for large vessel compliance. The investigators will use the combined CEU and euglycemic-hyperinsulinemic clamp approach to determine if microvascular and metabolic IR improves as a result.

Study Design

Study Type:
Interventional
Actual Enrollment :
0 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Each subject is studied 3 times in randomized orderEach subject is studied 3 times in randomized order
Masking:
None (Open Label)
Primary Purpose:
Basic Science
Official Title:
Effect of GLP-1 on Microvascular Insulin Responses in Type 1 Diabetes
Actual Study Start Date :
Oct 14, 2019
Anticipated Primary Completion Date :
Oct 1, 2023
Anticipated Study Completion Date :
Oct 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: GLP-1

GLP-1 infusion 1.2 pmol/kg/min for 150 min

Drug: GLP-1
glucagon-like peptide 1
Active Comparator: GLP-1 + Insulin clamp

GLP-1 infusion 1.2 pmol/kg/min for 150 min and insulin 1 mU/kg/min + Dextrose 20% at variable rate to maintain euglycemia for 120 min

Drug: GLP-1
glucagon-like peptide 1

Drug: Insulin
we are using to replace basal insulin and to raise insulin concentrations during the insulin clamp

Drug: Dextrose 20 % in Water
We are using Dextrose to maintain Euglycemia during the insulin clamp
Active Comparator: Saline + Insulin clamp

Saline infusion at 30 ml/hr for 150 min and insulin 1 mU/kg/min + Dextrose 20% at variable rate to maintain euglycemia for 120 min.

Drug: Insulin
we are using to replace basal insulin and to raise insulin concentrations during the insulin clamp

Drug: Dextrose 20 % in Water
We are using Dextrose to maintain Euglycemia during the insulin clamp

Outcome Measures

Primary Outcome Measures

  1. change in microvascular blood volume between baseline and 2 hour insulin clamp [baseline and after 2 hour insulin clamp]

    vascular measurement

  2. change in insulin sensitivity between baseline and 2 hour insulin clamp [baseline and after 2 hour insulin clamp]

    vascular measurement

Secondary Outcome Measures

  1. change in augmentation index between baseline and 2 hour insulin clamp [baseline and after 2 hour insulin clamp]

    vascular measurement

  2. change in flow-mediated dilation between baseline and 2 hour insulin clamp [baseline and after 2 hour insulin clamp]

    vascular measurement

  3. change in pulse wave velocity between baseline and 2 hour insulin clamp [baseline and after 2 hour insulin clamp]

    vascular measurement

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 40 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:

  1. History of type 1 diabetes, duration > 1 year

  2. Age 18-40 years

  3. HbA1c < 8.5%

  4. BMI >/=18, <30 kg/m2

  5. Using insulin for diabetes treatment only

  6. On stable regimen of non-diabetic medications for the last 6 months, excluding oral contraceptives (OCP)

  7. All screening labs within normal limits or not clinical significant

Exclusion Criteria:
  1. Pregnancy or currently breastfeeding 2) Smoking history within 6 months 3) History of microvascular (microalbuminuria, retinopathy, neuropathy) or macrovascular diabetes complications (coronary artery disease, stroke, peripheral vascular disease) 4) Taking vasoactive medications (i.e. calcium channel blockers, angiotensin-converting enzyme or renin inhibitors, angiotensin-receptor blockers, nitrates, alpha-blockers) 5) OCP use within 3 months or 1 month if menses has subsequently occurred 6) Known hypersensitivity to perflutren (contained in Definity© contrast) 7) Screening O2 saturation<90% 8) Anemia (hemoglobin <12 g/dL in women, hemoglobin <13 g/dL in men) 9) Diabetic ketoacidosis (DKA) on presentation to screening visits or study admission days

Contacts and Locations

Locations

Site City State Country Postal Code
1 University of Virginia Charlottesville Virginia United States 22906

Sponsors and Collaborators

  • University of Virginia
  • American Diabetes Association
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

  • Principal Investigator: Zhenqi Liu, MD, Department of Endocrinology, University of Virginia

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Zhenqi Liu, Deparment of Medicine, Chief of Div. Endocrinology, University of Virginia, University of Virginia
ClinicalTrials.gov Identifier:
NCT04133922
Other Study ID Numbers:
  • 21590
  • 5R01DK102359-03
First Posted:
Oct 21, 2019
Last Update Posted:
Mar 22, 2022
Last Verified:
Mar 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Insulin Resistance
Insulin

Study Results

No Results Posted as of Mar 22, 2022