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EJB050: Effect of Hyperglycemia on Microvascular Perfusion in Healthy Adults

Sponsor
University of Virginia (Other)
Overall Status
Completed
CT.gov ID
NCT03520569
Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
15
Enrollment
1
Location
4
Arms
25.9
Actual Duration (Months)
0.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The investigators are studying the effects of Hyperglycemia on vascular function and insulin sensitivity on healthy adults

Condition or Disease Intervention/Treatment Phase
Early Phase 1

Detailed Description

The investigators will study 22 healthy subjects (18-35 yrs) four times as follows:

  1. Saline + Octreotide + euglycemia;

  2. Octreotide + hyperglycemia;

  3. Octreotide + hyperglycemia + insulin clamp and

  4. 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:
  1. identify whether vascular stiffness and indices of NO action are impaired throughout the arterial tree with hyperglycemia.

Study Design

Study Type:
Interventional
Actual Enrollment :
15 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Intervention Model Description:
Each subject is studied 4 times in a randomized sequential orderEach subject is studied 4 times in a randomized sequential order
Masking:
None (Open Label)
Primary Purpose:
Basic Science
Official Title:
Effect of Hyperglycemia on Microvascular Perfusion in Healthy Adults
Actual Study Start Date :
Feb 4, 2019
Actual Primary Completion Date :
Apr 1, 2021
Actual Study Completion Date :
Apr 1, 2021

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Octreotide- Euglycemia

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

Drug: Octreotide
we are using it to block insulin secretion from the pancreas

Drug: Insulin
we are using to replace basal insulin and in two protocols to raise insulin concentrations during the insulin clamp

Drug: Dextrose 20% solution
We are using dextrose to maintain glycemia level
Active Comparator: Octreotide - Euglycemia- insulin clamp

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

Drug: Octreotide
we are using it to block insulin secretion from the pancreas

Drug: Insulin
we are using to replace basal insulin and in two protocols to raise insulin concentrations during the insulin clamp

Drug: Dextrose 20% solution
We are using dextrose to maintain glycemia level
Active Comparator: Octreotide- hyperglycemia

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

Drug: Octreotide
we are using it to block insulin secretion from the pancreas

Drug: Insulin
we are using to replace basal insulin and in two protocols to raise insulin concentrations during the insulin clamp

Drug: Dextrose 20% solution
We are using dextrose to maintain glycemia level
Active Comparator: Octreotide- hyperglycemia - insulin clamp

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

Drug: Octreotide
we are using it to block insulin secretion from the pancreas

Drug: Insulin
we are using to replace basal insulin and in two protocols to raise insulin concentrations during the insulin clamp

Drug: Dextrose 20% solution
We are using dextrose to maintain glycemia level

Outcome Measures

Primary Outcome Measures

  1. Change in Flow Mediated Dilation (FMD) Between Baseline and After 2 Hour Insulin Clamp [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

  1. Change in Augmentation Index Between Baseline and After 2 Hour Insulin Clamp [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.

  2. Change in Pulse Wave Velocity (PWV) Between Baseline and After 2 Hour Insulin Clamp [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

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 35 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
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)

Contacts and Locations

Locations

Site City State Country Postal Code
1 University of Virginia Charlottesville Virginia United States 22908

Sponsors and Collaborators

  • University of Virginia
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

None specified.

Study Documents (Full-Text)

More Information

Publications

Responsible Party:
Eugene Barrett, Prinicipal Investigator, University of Virginia
ClinicalTrials.gov Identifier:
NCT03520569
Other Study ID Numbers:
  • 19948
  • T32DK007646
First Posted:
May 9, 2018
Last Update Posted:
May 13, 2022
Last Verified:
Apr 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Insulin Resistance
Hyperglycemia
Octreotide

Study Results

Participant Flow

Recruitment Details 20 potential study participants were screened for eligibility
Pre-assignment Detail 15 participants were ultimately enrolled. Five potential subjects failed to meet inclusion criteria and were subsequently excluded from the study.
Arm/Group Title All Participants
Arm/Group Description All participants enrolled who completed at least one arm of the crossover assignment.
Period Title: Overall Study
STARTED 15
Octreotide-Euglycemia 13
Octreotide-Euglycemia-Insulin Clamp 14
Octreotide-Hyperglycemia 10
Octreotide-Hyperglycemia-Insulin Clamp 12
COMPLETED 14
NOT COMPLETED 1

Baseline Characteristics

Arm/Group Title All Participants
Arm/Group Description all participants who completed the study
Overall Participants 15
Age (Count of Participants)
<=18 years
0
0%
Between 18 and 65 years
15
100%
>=65 years
0
0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
24
(1)
Sex: Female, Male (Count of Participants)
Female
7
46.7%
Male
8
53.3%
Race/Ethnicity, Customized (Count of Participants)
caucasian
13
86.7%
african american
1
6.7%
asian
1
6.7%
Region of Enrollment (participants) [Number]
United States
15
100%

Outcome Measures

1. Primary Outcome
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

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Octreotide- Euglycemia Octreotide - Euglycemia- Insulin Clamp Octreotide- Hyperglycemia Octreotide- Hyperglycemia - Insulin Clamp
Arm/Group 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: we are using it to block insulin secretion from the pancreas Insulin: we are using to replace basal insulin and in two protocols to raise insulin concentrations during the insulin clamp Dextrose 20% solution: We are using dextrose to maintain glycemia level 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: we are using it to block insulin secretion from the pancreas Insulin: we are using to replace basal insulin and in two protocols to raise insulin concentrations during the insulin clamp Dextrose 20% solution: We are using dextrose to maintain glycemia level 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: we are using it to block insulin secretion from the pancreas Insulin: we are using to replace basal insulin and in two protocols to raise insulin concentrations during the insulin clamp Dextrose 20% solution: We are using dextrose to maintain glycemia level 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 Octreotide: we are using it to block insulin secretion from the pancreas Insulin: we are using to replace basal insulin and in two protocols to raise insulin concentrations during the insulin clamp Dextrose 20% solution: We are using dextrose to maintain glycemia level
Measure Participants 13 14 10 12
Mean (Standard Deviation) [% change]
11.8
(4.4)
11.8
(4)
8.9
(4.3)
8.95
(4.5)
2. Secondary Outcome
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

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Octreotide- Euglycemia Octreotide - Euglycemia- Insulin Clamp Octreotide- Hyperglycemia Octreotide- Hyperglycemia - Insulin Clamp
Arm/Group 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: we are using it to block insulin secretion from the pancreas Insulin: we are using to replace basal insulin and in two protocols to raise insulin concentrations during the insulin clamp Dextrose 20% solution: We are using dextrose to maintain glycemia level 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: we are using it to block insulin secretion from the pancreas Insulin: we are using to replace basal insulin and in two protocols to raise insulin concentrations during the insulin clamp Dextrose 20% solution: We are using dextrose to maintain glycemia level 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: we are using it to block insulin secretion from the pancreas Insulin: we are using to replace basal insulin and in two protocols to raise insulin concentrations during the insulin clamp Dextrose 20% solution: We are using dextrose to maintain glycemia level 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 Octreotide: we are using it to block insulin secretion from the pancreas Insulin: we are using to replace basal insulin and in two protocols to raise insulin concentrations during the insulin clamp Dextrose 20% solution: We are using dextrose to maintain glycemia level
Measure Participants 13 14 10 12
Mean (Standard Deviation) [percentage]
-4.15
(11.72)
-2.23
(12.33)
-4.80
(12.13)
-8.45
(9.16)
3. Secondary Outcome
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

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Octreotide- Euglycemia Octreotide - Euglycemia- Insulin Clamp Octreotide- Hyperglycemia Octreotide- Hyperglycemia - Insulin Clamp
Arm/Group 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: we are using it to block insulin secretion from the pancreas Insulin: we are using to replace basal insulin and in two protocols to raise insulin concentrations during the insulin clamp Dextrose 20% solution: We are using dextrose to maintain glycemia level 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: we are using it to block insulin secretion from the pancreas Insulin: we are using to replace basal insulin and in two protocols to raise insulin concentrations during the insulin clamp Dextrose 20% solution: We are using dextrose to maintain glycemia level 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: we are using it to block insulin secretion from the pancreas Insulin: we are using to replace basal insulin and in two protocols to raise insulin concentrations during the insulin clamp Dextrose 20% solution: We are using dextrose to maintain glycemia level 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 Octreotide: we are using it to block insulin secretion from the pancreas Insulin: we are using to replace basal insulin and in two protocols to raise insulin concentrations during the insulin clamp Dextrose 20% solution: We are using dextrose to maintain glycemia level
Measure Participants 13 14 10 12
Mean (Standard Deviation) [m/sec]
5.21
(0.64)
5.06
(0.76)
4.79
(0.79)
5.07
(0.67)

Adverse Events

Time Frame 20 months
Adverse Event Reporting Description
Arm/Group Title Octreotide- Euglycemia Octreotide - Euglycemia- Insulin Clamp Octreotide- Hyperglycemia Octreotide- Hyperglycemia - Insulin Clamp
Arm/Group 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: we are using it to block insulin secretion from the pancreas Insulin: we are using to replace basal insulin and in two protocols to raise insulin concentrations during the insulin clamp Dextrose 20% solution: We are using dextrose to maintain glycemia level 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: we are using it to block insulin secretion from the pancreas Insulin: we are using to replace basal insulin and in two protocols to raise insulin concentrations during the insulin clamp Dextrose 20% solution: We are using dextrose to maintain glycemia level 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: we are using it to block insulin secretion from the pancreas Insulin: we are using to replace basal insulin and in two protocols to raise insulin concentrations during the insulin clamp Dextrose 20% solution: We are using dextrose to maintain glycemia level 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 Octreotide: we are using it to block insulin secretion from the pancreas Insulin: we are using to replace basal insulin and in two protocols to raise insulin concentrations during the insulin clamp Dextrose 20% solution: We are using dextrose to maintain glycemia level
All Cause Mortality
Octreotide- Euglycemia Octreotide - Euglycemia- Insulin Clamp Octreotide- Hyperglycemia Octreotide- Hyperglycemia - Insulin Clamp
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/13 (0%) 0/14 (0%) 0/10 (0%) 0/12 (0%)
Serious Adverse Events
Octreotide- Euglycemia Octreotide - Euglycemia- Insulin Clamp Octreotide- Hyperglycemia Octreotide- Hyperglycemia - Insulin Clamp
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/13 (0%) 0/14 (0%) 0/10 (0%) 0/12 (0%)
Other (Not Including Serious) Adverse Events
Octreotide- Euglycemia Octreotide - Euglycemia- Insulin Clamp Octreotide- Hyperglycemia Octreotide- Hyperglycemia - Insulin Clamp
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/13 (0%) 0/14 (0%) 0/10 (0%) 0/12 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title Eugene Barrett
Organization University of Virginia
Phone 434-924-1263
Email EJB8X@VIRGINIA.EDU
Responsible Party:
Eugene Barrett, Prinicipal Investigator, University of Virginia
ClinicalTrials.gov Identifier:
NCT03520569
Other Study ID Numbers:
  • 19948
  • T32DK007646
First Posted:
May 9, 2018
Last Update Posted:
May 13, 2022
Last Verified:
Apr 1, 2022