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

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ClinicalTrials.gov Identifier: NCT04133922
Recruitment Status : Recruiting
First Posted : October 21, 2019
Last Update Posted : October 21, 2019
Sponsor:
Collaborators:
American Diabetes Association
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Zhenqi Liu, MD, University of Virginia

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
Type 1 Diabetes Insulin Sensitivity/Resistance Drug: GLP-1 Drug: Insulin Drug: Dextrose 20 % in Water 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Each 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 : October 14, 2019
Estimated Primary Completion Date : October 2023
Estimated Study Completion Date : October 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1

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




Primary Outcome Measures :
  1. change in microvascular blood volume between baseline and 2 hour insulin clamp [ Time Frame: baseline and after 2 hour insulin clamp ]
    vascular measurement

  2. change in insulin sensitivity between baseline and 2 hour insulin clamp [ Time Frame: baseline and after 2 hour insulin clamp ]
    vascular measurement


Secondary Outcome Measures :
  1. change in augmentation index between baseline and 2 hour insulin clamp [ Time Frame: baseline and after 2 hour insulin clamp ]
    vascular measurement

  2. change in flow-mediated dilation between baseline and 2 hour insulin clamp [ Time Frame: baseline and after 2 hour insulin clamp ]
    vascular measurement

  3. change in pulse wave velocity between baseline and 2 hour insulin clamp [ Time Frame: baseline and after 2 hour insulin clamp ]
    vascular measurement



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

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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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04133922


Contacts
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Contact: Lee Hartline, MEd 434-924-5247 lmh9d@virginia.edu
Contact: Linda Jahn, MEd 434-924-1134 las6e@virginia.edu

Locations
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United States, Virginia
University of Virginia Recruiting
Charlottesville, Virginia, United States, 22906
Contact: Zhenqi Liu, MD    434-243-2603    zl3e@virginia.edu   
Contact: Eugene Barrett, MD, PhD    434-924-1175    ejb8x@virginia.edu   
Sponsors and Collaborators
University of Virginia
American Diabetes Association
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
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Principal Investigator: Zhenqi Liu, MD Department of Endocrinology, University of Virginia

Publications:

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Responsible Party: Zhenqi Liu, MD, Deparment of Medicine, Chief of Div. Endocrinology, University of Virginia, University of Virginia
ClinicalTrials.gov Identifier: NCT04133922     History of Changes
Other Study ID Numbers: 21590
5R01DK102359-03 ( U.S. NIH Grant/Contract )
First Posted: October 21, 2019    Key Record Dates
Last Update Posted: October 21, 2019
Last Verified: October 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Insulin Resistance
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Hyperinsulinism
Insulin
Insulin, Globin Zinc
Glucagon
Glucagon-Like Peptide 1
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Gastrointestinal Agents