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

March 7, 2022 updated by: Zhenqi Liu, University of Virginia
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

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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 Type

Interventional

Phase

  • Early Phase 1

Contacts and Locations

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

Study Locations

  • United States
    • Virginia
      • Charlottesville, Virginia, United States, 22906
        • University of Virginia

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

Genders Eligible for Study

All

Description

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

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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: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
change in microvascular blood volume between baseline and 2 hour insulin clamp
Time Frame: baseline and after 2 hour insulin clamp
vascular measurement
baseline and after 2 hour insulin clamp
change in insulin sensitivity between baseline and 2 hour insulin clamp
Time Frame: baseline and after 2 hour insulin clamp
vascular measurement
baseline and after 2 hour insulin clamp

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
change in augmentation index between baseline and 2 hour insulin clamp
Time Frame: baseline and after 2 hour insulin clamp
vascular measurement
baseline and after 2 hour insulin clamp
change in flow-mediated dilation between baseline and 2 hour insulin clamp
Time Frame: baseline and after 2 hour insulin clamp
vascular measurement
baseline and after 2 hour insulin clamp
change in pulse wave velocity between baseline and 2 hour insulin clamp
Time Frame: baseline and after 2 hour insulin clamp
vascular measurement
baseline and after 2 hour insulin clamp

Collaborators and Investigators

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

Sponsor

University of Virginia

Collaborators

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

Investigators

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

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 14, 2019

Primary Completion (Anticipated)

October 1, 2023

Study Completion (Anticipated)

October 1, 2024

Study Registration Dates

First Submitted

October 15, 2019

First Submitted That Met QC Criteria

October 17, 2019

First Posted (Actual)

October 21, 2019

Study Record Updates

Last Update Posted (Actual)

March 22, 2022

Last Update Submitted That Met QC Criteria

March 7, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 21590
  • 5R01DK102359-03 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

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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