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

Type 1 Diabetes Clinical Trial

— KML001  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04133922
• Other study ID #: 21590
• Secondary ID: 5R01DK102359-03
• Status: Withdrawn
• Phase: Early Phase 1
• Start date: October 14, 2019
• Est. completion date: October 2024

Study information

• Verified date: March 2022
• Source: University of Virginia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: October 2024
• Est. primary completion date: October 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

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 -

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Insulin Resistance
• Insulin Sensitivity/Resistance
• Type 1 Diabetes

Intervention

Drug:
• GLP-1
glucagon-like peptide 1
• Insulin
we are using to replace basal insulin and to raise insulin concentrations during the insulin clamp
• Dextrose 20 % in Water
We are using Dextrose to maintain Euglycemia during the insulin clamp

Locations

Country	Name	City	State
United States	University of Virginia	Charlottesville	Virginia

Sponsors (3)

Lead Sponsor	Collaborator
University of Virginia	American Diabetes Association, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (30)

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* Note: There are 30 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	change in microvascular blood volume between baseline and 2 hour insulin clamp	vascular measurement	baseline and after 2 hour insulin clamp
Primary	change in insulin sensitivity between baseline and 2 hour insulin clamp	vascular measurement	baseline and after 2 hour insulin clamp
Secondary	change in augmentation index between baseline and 2 hour insulin clamp	vascular measurement	baseline and after 2 hour insulin clamp
Secondary	change in flow-mediated dilation between baseline and 2 hour insulin clamp	vascular measurement	baseline and after 2 hour insulin clamp
Secondary	change in pulse wave velocity between baseline and 2 hour insulin clamp	vascular measurement	baseline and after 2 hour insulin clamp