Effect of Hyperglycemia on Microvascular Perfusion in Healthy Adults

Early Phase 1

Completed

• Conditions: Vascular Stiffness; Insulin Sensitivity
• Interventions: Drug: Octreotide; Drug: Insulin; Drug: Dextrose 20% solution

• Registration Number: NCT03520569
• Lead Sponsor: University of Virginia

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:

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:

a) identify whether vascular stiffness and indices of NO action are impaired throughout the arterial tree with hyperglycemia.

Study Timeline

• Study First Submitted: 2018-03-08
• Study First Submitted QC: 2018-05-08
• Study First Posted: 2018-05-09
• Study Start: 2019-02-04
• Primary Completion: 2021-04-01
• Study Completion: 2021-04-01
• Results First Submitted: 2022-02-09
• Status Verified: 2022-04
• Results First Submitted QC: 2022-04-20
• Last Update Submitted: 2022-04-20
• Results First Posted: 2022-05-13
• Last Update Posted: 2022-05-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

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

Read More

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)

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Octreotide- hyperglycemia - insulin clamp	Dextrose 20% solution	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- Euglycemia	Octreotide	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- Euglycemia	Insulin	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- Euglycemia	Dextrose 20% solution	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 - Euglycemia- insulin clamp	Insulin	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 - Euglycemia- insulin clamp	Dextrose 20% solution	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- hyperglycemia	Octreotide	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- hyperglycemia	Insulin	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- hyperglycemia	Dextrose 20% solution	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- hyperglycemia - insulin clamp	Insulin	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 - Euglycemia- insulin clamp	Octreotide	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- hyperglycemia - insulin clamp	Octreotide	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

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.
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

Trial Locations

Locations (1)

University of Virginia; 🇺🇸 Charlottesville, Virginia, United States