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

NCT04133922 | Withdrawn Early Phase 1 FDA Drug

• 2 other identifiers: 215905R01DK102359-03
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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

Conditions

Type 1 Diabetes; Insulin Sensitivity/Resistance

Outcome Measures

Primary Outcomes (2)

• change in microvascular blood volume between baseline and 2 hour insulin clamp

  vascular measurement

  baseline and after 2 hour insulin clamp

• change in insulin sensitivity between baseline and 2 hour insulin clamp

  vascular measurement

  baseline and after 2 hour insulin clamp

Secondary Outcomes (3)

• change in augmentation index between baseline and 2 hour insulin clamp

  baseline and after 2 hour insulin clamp

• change in flow-mediated dilation between baseline and 2 hour insulin clamp

  baseline and after 2 hour insulin clamp

• change in pulse wave velocity between baseline and 2 hour insulin clamp

  baseline and after 2 hour insulin clamp

Study Arms (3)

GLP-1

ACTIVE COMPARATOR

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

Drug: GLP-1

GLP-1 + Insulin clamp

ACTIVE COMPARATOR

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; Drug: Insulin; Drug: Dextrose 20 % in Water

Saline + Insulin clamp

ACTIVE COMPARATOR

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; Drug: Dextrose 20 % in Water

Interventions

GLP-1 DRUG

glucagon-like peptide 1

GLP-1; GLP-1 + Insulin clamp

Insulin DRUG

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

GLP-1 + Insulin clamp; Saline + Insulin clamp

Dextrose 20 % in Water DRUG

We are using Dextrose to maintain Euglycemia during the insulin clamp

GLP-1 + Insulin clamp; Saline + Insulin clamp

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• \) 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

Sponsors & Collaborators

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

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22906, United States

Location

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MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Insulin Resistance

Interventions

Glucagon-Like Peptide 1; Insulin; Glucose; Water

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins; Hexoses; Monosaccharides; Sugars; Carbohydrates; Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds

Study Officials

• Zhenqi Liu, MD

  Department of Endocrinology, University of Virginia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deparment of Medicine, Chief of Div. Endocrinology, University of Virginia

Model Details: Each subject is studied 3 times in randomized order

Study Record Dates

• First Submitted: October 15, 2019
• First Posted: October 21, 2019
• Study Start: October 14, 2019
• Primary Completion: October 1, 2023
• Study Completion: October 1, 2024
• Last Updated: March 22, 2022

Record last verified: 2022-03

Locations

US (1)