Back to resultsEffect of GLP-1 on Microvascular Insulin Responses in Type 1 Diabetes (KML001)
Primary Purpose
Type 1 Diabetes, Insulin Sensitivity/Resistance
Status
Withdrawn
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
GLP-1
Insulin
Dextrose 20 % in Water
Sponsored by
About this trial
This is an interventional basic science trial for Type 1 Diabetes
Eligibility Criteria
Inclusion Criteria:
- History of type 1 diabetes, duration > 1 year
- Age 18-40 years
- HbA1c < 8.5%
- BMI >/=18, <30 kg/m2
- Using insulin for diabetes treatment only
- On stable regimen of non-diabetic medications for the last 6 months, excluding oral contraceptives (OCP)
- 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
-
Sites / Locations
- University of Virginia
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Active Comparator
Arm Label
GLP-1
GLP-1 + Insulin clamp
Saline + Insulin clamp
Arm Description
GLP-1 infusion 1.2 pmol/kg/min for 150 min
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
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.
Outcomes
Primary Outcome Measures
change in microvascular blood volume between baseline and 2 hour insulin clamp
vascular measurement
change in insulin sensitivity between baseline and 2 hour insulin clamp
vascular measurement
Secondary Outcome Measures
change in augmentation index between baseline and 2 hour insulin clamp
vascular measurement
change in flow-mediated dilation between baseline and 2 hour insulin clamp
vascular measurement
change in pulse wave velocity between baseline and 2 hour insulin clamp
vascular measurement
Full Information
NCT ID
NCT04133922
First Posted
October 15, 2019
Last Updated
March 7, 2022
Sponsor
University of Virginia
Collaborators
American Diabetes Association, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1. Study Identification
Unique Protocol Identification Number
NCT04133922
Brief Title
Effect of GLP-1 on Microvascular Insulin Responses in Type 1 Diabetes
Acronym
KML001
Official Title
Effect of GLP-1 on Microvascular Insulin Responses in Type 1 Diabetes
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Withdrawn
Why Stopped
the study drug could not be obtained
Study Start Date
October 14, 2019 (Actual)
Primary Completion Date
October 2023 (Anticipated)
Study Completion Date
October 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Virginia
Collaborators
American Diabetes Association, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes, Insulin Sensitivity/Resistance
7. Study Design
Primary Purpose
Basic Science
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Model Description
Each subject is studied 3 times in randomized order
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
GLP-1
Arm Type
Active Comparator
Arm Description
GLP-1 infusion 1.2 pmol/kg/min for 150 min
Arm Title
GLP-1 + Insulin clamp
Arm Type
Active Comparator
Arm Description
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
Arm Title
Saline + Insulin clamp
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
GLP-1
Intervention Description
glucagon-like peptide 1
Intervention Type
Drug
Intervention Name(s)
Insulin
Intervention Description
we are using to replace basal insulin and to raise insulin concentrations during the insulin clamp
Intervention Type
Drug
Intervention Name(s)
Dextrose 20 % in Water
Intervention Description
We are using Dextrose to maintain Euglycemia during the insulin clamp
Primary Outcome Measure Information:
Title
change in microvascular blood volume between baseline and 2 hour insulin clamp
Description
vascular measurement
Time Frame
baseline and after 2 hour insulin clamp
Title
change in insulin sensitivity between baseline and 2 hour insulin clamp
Description
vascular measurement
Time Frame
baseline and after 2 hour insulin clamp
Secondary Outcome Measure Information:
Title
change in augmentation index between baseline and 2 hour insulin clamp
Description
vascular measurement
Time Frame
baseline and after 2 hour insulin clamp
Title
change in flow-mediated dilation between baseline and 2 hour insulin clamp
Description
vascular measurement
Time Frame
baseline and after 2 hour insulin clamp
Title
change in pulse wave velocity between baseline and 2 hour insulin clamp
Description
vascular measurement
Time Frame
baseline and after 2 hour insulin clamp
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
History of type 1 diabetes, duration > 1 year
Age 18-40 years
HbA1c < 8.5%
BMI >/=18, <30 kg/m2
Using insulin for diabetes treatment only
On stable regimen of non-diabetic medications for the last 6 months, excluding oral contraceptives (OCP)
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
-
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhenqi Liu, MD
Organizational Affiliation
Department of Endocrinology, University of Virginia
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22906
Country
United States
12. IPD Sharing Statement
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Effect of GLP-1 on Microvascular Insulin Responses in Type 1 Diabetes
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