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Effect of Hyperglycemia on Microvascular Perfusion in Healthy Adults (EJB050)

Primary Purpose

Vascular Stiffness, Insulin Sensitivity

Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Octreotide
Insulin
Dextrose 20% solution
Sponsored by
University of Virginia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Vascular Stiffness

Eligibility Criteria

18 Years - 35 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Healthy with no chronic illness
  • Age 18-35
  • Normal BMI (18-25)
  • Normal screening labs or no clinically significant values

Exclusion Criteria:

  • First degree relative with Type 2 Diabetes
  • Smoking presently or in the past 6 months
  • Medications that affect the vasculature
  • Overweight or other indications of insulin resistance
  • Elevated LDL cholesterol > 160
  • Elevated BP > 140/90
  • History of congestive heart failure, ischemic heart disease, severe pulmonary disease, liver or kidney disease, bleeding disorders
  • Any vascular disease such as myocardial infarction, stroke, peripheral vascular disease
  • Presence of an intracardiac or intrapulmonary shunt (we will screen for this by auscultation during the physical exam by PI).
  • Pregnant or breastfeeding.
  • Known hypersensitivity to perflutren (contained in Definity)

Sites / Locations

  • University of Virginia

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Arm Label

Octreotide- Euglycemia

Octreotide - Euglycemia- insulin clamp

Octreotide- hyperglycemia

Octreotide- hyperglycemia - insulin clamp

Arm Description

octreotide is 30 ng/kg/min x 240 min insulin 0.15mU/kg/min x 240 min Dextrose 20% at variable rate to maintain euglycemia for 240 min

octreotide is 30 ng/kg/min x 330 min insulin 0.15mU/kg/min x 210 min insulin 1.0mU/kg/min x 120 min Dextrose 20% at variable rate to maintain euglycemia for 330 min

octreotide is 30 ng/kg/min x 330 min insulin 0.15mU/kg/min x 330 min Dextrose 20% at variable rate to maintain euglycemia for 90 min Dextrose 20% at variable rate to maintain hyperglycemia for 240 min

octreotide is 30 ng/kg/min x 330 min insulin 0.15mU/kg/min x 210 min insulin 1.0mU/kg/min x 120 min Dextrose 20% at variable rate to maintain euglycemia for 90 min Dextrose 20% at variable rate to maintain hyperglycemia for 240 min

Outcomes

Primary Outcome Measures

Change in Flow Mediated Dilation (FMD) Between Baseline and After 2 Hour Insulin Clamp
Flow mediated dilation measures the change in brachial diameter in response to 5 minutes of ischemia using B-mode ultrasound. It provides an index of nitric oxide generation by the endothelium .

Secondary Outcome Measures

Change in Augmentation Index Between Baseline and After 2 Hour Insulin Clamp
The augmentation index (AIx) measured at the radial artery is a measure of systemic arterial stiffness, and is defined as the ratio of augmentation (Δ P) to central pulse pressure and expressed as percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. Higher percentages indicate increased arterial stiffness.
Change in Pulse Wave Velocity (PWV) Between Baseline and After 2 Hour Insulin Clamp
The time required for a blood pressure wave to travel from the carotid to the femoral artery was measured in meter/sec. This is a measurement of central artery stiffness. Higher numbers indicate stiffer vessels

Full Information

First Posted
March 8, 2018
Last Updated
April 20, 2022
Sponsor
University of Virginia
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT03520569
Brief Title
Effect of Hyperglycemia on Microvascular Perfusion in Healthy Adults
Acronym
EJB050
Official Title
Effect of Hyperglycemia on Microvascular Perfusion in Healthy Adults
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
February 4, 2019 (Actual)
Primary Completion Date
April 1, 2021 (Actual)
Study Completion Date
April 1, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Virginia
Collaborators
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
The investigators are studying the effects of Hyperglycemia on vascular function and insulin sensitivity on healthy adults
Detailed Description
The investigators will study 22 healthy subjects (18-35 yrs) four times as follows: Saline + Octreotide + euglycemia; Octreotide + hyperglycemia; Octreotide + hyperglycemia + insulin clamp and Octreotide + Euglycemia + insulin clamp. The sequence of admissions will be assigned randomly. The investigators will assess function in conduit (pulse wave velocity-PWV, augmentation index-AI and flow-mediated dilation-FMD), resistance (post-ischemic flow velocity-PIFV) and heart and skeletal muscle microvascular (contrast enhanced ultrasound-CEU) vessels. This work will: a) identify whether vascular stiffness and indices of NO action are impaired throughout the arterial tree with hyperglycemia.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Vascular Stiffness, Insulin Sensitivity

7. Study Design

Primary Purpose
Basic Science
Study Phase
Early Phase 1
Interventional Study Model
Crossover Assignment
Model Description
Each subject is studied 4 times in a randomized sequential order
Masking
None (Open Label)
Allocation
Randomized
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Octreotide- Euglycemia
Arm Type
Active Comparator
Arm Description
octreotide is 30 ng/kg/min x 240 min insulin 0.15mU/kg/min x 240 min Dextrose 20% at variable rate to maintain euglycemia for 240 min
Arm Title
Octreotide - Euglycemia- insulin clamp
Arm Type
Active Comparator
Arm Description
octreotide is 30 ng/kg/min x 330 min insulin 0.15mU/kg/min x 210 min insulin 1.0mU/kg/min x 120 min Dextrose 20% at variable rate to maintain euglycemia for 330 min
Arm Title
Octreotide- hyperglycemia
Arm Type
Active Comparator
Arm Description
octreotide is 30 ng/kg/min x 330 min insulin 0.15mU/kg/min x 330 min Dextrose 20% at variable rate to maintain euglycemia for 90 min Dextrose 20% at variable rate to maintain hyperglycemia for 240 min
Arm Title
Octreotide- hyperglycemia - insulin clamp
Arm Type
Active Comparator
Arm Description
octreotide is 30 ng/kg/min x 330 min insulin 0.15mU/kg/min x 210 min insulin 1.0mU/kg/min x 120 min Dextrose 20% at variable rate to maintain euglycemia for 90 min Dextrose 20% at variable rate to maintain hyperglycemia for 240 min
Intervention Type
Drug
Intervention Name(s)
Octreotide
Intervention Description
we are using it to block insulin secretion from the pancreas
Intervention Type
Drug
Intervention Name(s)
Insulin
Intervention Description
we are using to replace basal insulin and in two protocols to raise insulin concentrations during the insulin clamp
Intervention Type
Drug
Intervention Name(s)
Dextrose 20% solution
Intervention Description
We are using dextrose to maintain glycemia level
Primary Outcome Measure Information:
Title
Change in Flow Mediated Dilation (FMD) Between Baseline and After 2 Hour Insulin Clamp
Description
Flow mediated dilation measures the change in brachial diameter in response to 5 minutes of ischemia using B-mode ultrasound. It provides an index of nitric oxide generation by the endothelium .
Time Frame
baseline and after 2 hour insulin clamp
Secondary Outcome Measure Information:
Title
Change in Augmentation Index Between Baseline and After 2 Hour Insulin Clamp
Description
The augmentation index (AIx) measured at the radial artery is a measure of systemic arterial stiffness, and is defined as the ratio of augmentation (Δ P) to central pulse pressure and expressed as percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. Higher percentages indicate increased arterial stiffness.
Time Frame
baseline and after 2 hour insulin clamp
Title
Change in Pulse Wave Velocity (PWV) Between Baseline and After 2 Hour Insulin Clamp
Description
The time required for a blood pressure wave to travel from the carotid to the femoral artery was measured in meter/sec. This is a measurement of central artery stiffness. Higher numbers indicate stiffer vessels
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
35 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Healthy with no chronic illness Age 18-35 Normal BMI (18-25) Normal screening labs or no clinically significant values Exclusion Criteria: First degree relative with Type 2 Diabetes Smoking presently or in the past 6 months Medications that affect the vasculature Overweight or other indications of insulin resistance Elevated LDL cholesterol > 160 Elevated BP > 140/90 History of congestive heart failure, ischemic heart disease, severe pulmonary disease, liver or kidney disease, bleeding disorders Any vascular disease such as myocardial infarction, stroke, peripheral vascular disease Presence of an intracardiac or intrapulmonary shunt (we will screen for this by auscultation during the physical exam by PI). Pregnant or breastfeeding. Known hypersensitivity to perflutren (contained in Definity)
Facility Information:
Facility Name
University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
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Effect of Hyperglycemia on Microvascular Perfusion in Healthy Adults

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