search
Back to results

Effects of Empagliflozin on Cardiac Microvasculature and Insulin Sensitivity in Subjects With Type 2 Diabetes (EJB051)

Primary Purpose

Type2 Diabetes, Insulin Sensitivity

Status
Recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Empagliflozin 25 MG
Sponsored by
University of Virginia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Type2 Diabetes

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • A1C > 6.5 and <9%
  • Never on SGLT-2i (eg: Jardiance, Invokana, Farxiga, Steglatro)
  • On stable dose of oral hypoglycemic agents >3 months
  • On stable dose of other medications for >3 months
  • BMI-<35

Exclusion Criteria:

  • • Smoking presently or in the past 6 months

    • Taking insulin
    • BP >160/90
    • BMI >35
    • History of congestive heart failure, ischemic heart disease, severe pulmonary disease, liver or kidney disease.
    • Any vascular disease such as myocardial infarction, stroke, peripheral vascular disease
    • History of cancer or psychiatric 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)
    • Screening O2 saturation <90%
    • History of recurrent UTI/bladder/kidney infections-eGFR is below 45 mL/min/1.73.

Sites / Locations

  • University of VirginiaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Empagliflozin + insulin infusion

Empagliflozin + mixed meal

Arm Description

vascular measurements in overnight fasted state and during insulin infusion

vascular measurements in overnight fasted state and 2 hours after mixed meal 10kcal/kg body weight ( 55% Cho, 30%Fat, 20% Pro)

Outcomes

Primary Outcome Measures

Myocardial microvascular perfusion
Vascular measure of myocardial perfusion

Secondary Outcome Measures

Flow Mediated Dilation (FMD) Vascular measure of conduit artery stiffness Change in Flow Mediated Dilation (FMD) between baseline and after 2 hour insulin clamp Vascular measure of conduit artery stiffness Flow Mediated Dilation ( FMD)
Vascular measure of conduit artery stiffness
Augmentation Index ( AI)
Measurement of central artery stiffness
Pulse Wave Velocity ( PWV)
Measurement of central artery stiffness

Full Information

First Posted
December 17, 2019
Last Updated
February 9, 2022
Sponsor
University of Virginia
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
search

1. Study Identification

Unique Protocol Identification Number
NCT04203927
Brief Title
Effects of Empagliflozin on Cardiac Microvasculature and Insulin Sensitivity in Subjects With Type 2 Diabetes
Acronym
EJB051
Official Title
Effects of Empagliflozin on Cardiac Microvasculature and Insulin Sensitivity in Subjects With Type 2 Diabetes
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 1, 2020 (Actual)
Primary Completion Date
October 30, 2023 (Anticipated)
Study Completion Date
November 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Virginia
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The aim is to test in T2DM patients, whether, compared to placebo, 12 weeks of SGLT-2 inhibitor improves post-absorptive, post-insulin infusion or postprandial insulin action to enhance Cardiac Muscle vascular function and whether changes correlate with improved GV or postprandial hyperglycemia
Detailed Description
The investigators will study 32 T2DM subjects measuring cardiac muscle vascular function before and after a 4 hour insulin clamp ( protocol A) and before and after a mixed meal (protocol B). Then subjects will be randomized into 2 groups: Group 1 will undergo a 12 week intervention of Empagliflozin, and Group 2 will do 12 weeks of Placebo. The intervention will be single blinded. At the end of the 12 week intervention subjects will repeat protocol A and B. The study's primary objective is to assess whether, compared to placebo, 12 weeks of Empagliflozin improves post-absorptive or postprandial insulin action to enhance myocardial perfusion (MP) and whether changes of MP correlate with improved glucose variability or postprandial hyperglycemia

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type2 Diabetes, Insulin Sensitivity

7. Study Design

Primary Purpose
Basic Science
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Empagliflozin + insulin infusion
Arm Type
Active Comparator
Arm Description
vascular measurements in overnight fasted state and during insulin infusion
Arm Title
Empagliflozin + mixed meal
Arm Type
Active Comparator
Arm Description
vascular measurements in overnight fasted state and 2 hours after mixed meal 10kcal/kg body weight ( 55% Cho, 30%Fat, 20% Pro)
Intervention Type
Drug
Intervention Name(s)
Empagliflozin 25 MG
Intervention Description
SGLT-2 inhibitor
Primary Outcome Measure Information:
Title
Myocardial microvascular perfusion
Description
Vascular measure of myocardial perfusion
Time Frame
Between baseline and 12 weeks treatment
Secondary Outcome Measure Information:
Title
Flow Mediated Dilation (FMD) Vascular measure of conduit artery stiffness Change in Flow Mediated Dilation (FMD) between baseline and after 2 hour insulin clamp Vascular measure of conduit artery stiffness Flow Mediated Dilation ( FMD)
Description
Vascular measure of conduit artery stiffness
Time Frame
Between baseline and 12 weeks of treatment.
Title
Augmentation Index ( AI)
Description
Measurement of central artery stiffness
Time Frame
Between baseline and 12 weeks of treatment.
Title
Pulse Wave Velocity ( PWV)
Description
Measurement of central artery stiffness
Time Frame
Between baseline and 12 weeks of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: A1C > 6.5 and <9% Never on SGLT-2i (eg: Jardiance, Invokana, Farxiga, Steglatro) On stable dose of oral hypoglycemic agents >3 months On stable dose of other medications for >3 months BMI-<35 Exclusion Criteria: • Smoking presently or in the past 6 months Taking insulin BP >160/90 BMI >35 History of congestive heart failure, ischemic heart disease, severe pulmonary disease, liver or kidney disease. Any vascular disease such as myocardial infarction, stroke, peripheral vascular disease History of cancer or psychiatric 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) Screening O2 saturation <90% History of recurrent UTI/bladder/kidney infections-eGFR is below 45 mL/min/1.73.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Eugene J Barrett, MD PhD
Phone
434-924-1263
Email
ejb8x@virginia.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Lee Hartline, MEd
Phone
434-924-5247
Email
lmh9d@virginia.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eugene J Barrett, MD PhD
Organizational Affiliation
University of Virginia
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22906
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eugene Barrett, MD, PhD
Phone
434-924-1175
Email
ejb8x@virginia.edu
First Name & Middle Initial & Last Name & Degree
Zhenqi Liu, MD
Email
zl3e@virginia.edu

12. IPD Sharing Statement

Citations:
PubMed Identifier
25633683
Citation
Nishimura R, Tanaka Y, Koiwai K, Inoue K, Hach T, Salsali A, Lund SS, Broedl UC. Effect of empagliflozin monotherapy on postprandial glucose and 24-hour glucose variability in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled, 4-week study. Cardiovasc Diabetol. 2015 Jan 30;14:11. doi: 10.1186/s12933-014-0169-9.
Results Reference
background
PubMed Identifier
29203583
Citation
Inzucchi SE, Zinman B, Fitchett D, Wanner C, Ferrannini E, Schumacher M, Schmoor C, Ohneberg K, Johansen OE, George JT, Hantel S, Bluhmki E, Lachin JM. How Does Empagliflozin Reduce Cardiovascular Mortality? Insights From a Mediation Analysis of the EMPA-REG OUTCOME Trial. Diabetes Care. 2018 Feb;41(2):356-363. doi: 10.2337/dc17-1096. Epub 2017 Dec 4.
Results Reference
background
PubMed Identifier
23459195
Citation
Zhao L, Chai W, Fu Z, Dong Z, Aylor KW, Barrett EJ, Cao W, Liu Z. Globular adiponectin enhances muscle insulin action via microvascular recruitment and increased insulin delivery. Circ Res. 2013 Apr 26;112(9):1263-71. doi: 10.1161/CIRCRESAHA.111.300388. Epub 2013 Mar 4.
Results Reference
background
PubMed Identifier
21047922
Citation
Liu J, Jahn LA, Fowler DE, Barrett EJ, Cao W, Liu Z. Free fatty acids induce insulin resistance in both cardiac and skeletal muscle microvasculature in humans. J Clin Endocrinol Metab. 2011 Feb;96(2):438-46. doi: 10.1210/jc.2010-1174. Epub 2010 Nov 3.
Results Reference
background
PubMed Identifier
15998667
Citation
Scognamiglio R, Negut C, De Kreutzenberg SV, Tiengo A, Avogaro A. Postprandial myocardial perfusion in healthy subjects and in type 2 diabetic patients. Circulation. 2005 Jul 12;112(2):179-84. doi: 10.1161/CIRCULATIONAHA.104.495127. Epub 2005 Jul 5.
Results Reference
background
PubMed Identifier
21617098
Citation
Chai W, Liu J, Jahn LA, Fowler DE, Barrett EJ, Liu Z. Salsalate attenuates free fatty acid-induced microvascular and metabolic insulin resistance in humans. Diabetes Care. 2011 Jul;34(7):1634-8. doi: 10.2337/dc10-2345. Epub 2011 May 26.
Results Reference
background
PubMed Identifier
16386091
Citation
Kovatchev BP, Clarke WL, Breton M, Brayman K, McCall A. Quantifying temporal glucose variability in diabetes via continuous glucose monitoring: mathematical methods and clinical application. Diabetes Technol Ther. 2005 Dec;7(6):849-62. doi: 10.1089/dia.2005.7.849.
Results Reference
background
PubMed Identifier
28304392
Citation
Kovatchev BP. Metrics for glycaemic control - from HbA1c to continuous glucose monitoring. Nat Rev Endocrinol. 2017 Jul;13(7):425-436. doi: 10.1038/nrendo.2017.3. Epub 2017 Mar 17.
Results Reference
background
PubMed Identifier
26981940
Citation
Zinman B, Lachin JM, Inzucchi SE. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2016 Mar 17;374(11):1094. doi: 10.1056/NEJMc1600827. No abstract available.
Results Reference
background
PubMed Identifier
29166232
Citation
Neal B, Perkovic V, Matthews DR. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017 Nov 23;377(21):2099. doi: 10.1056/NEJMc1712572. No abstract available.
Results Reference
background
PubMed Identifier
27299675
Citation
Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von Eynatten M, Mattheus M, Johansen OE, Woerle HJ, Broedl UC, Zinman B; EMPA-REG OUTCOME Investigators. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N Engl J Med. 2016 Jul 28;375(4):323-34. doi: 10.1056/NEJMoa1515920. Epub 2016 Jun 14.
Results Reference
background
PubMed Identifier
16308832
Citation
Kolka CM, Rattigan S, Richards SM, Barrett EJ, Clark MG. Endothelial Na+-D-glucose cotransporter: no role in insulin-mediated glucose uptake. Horm Metab Res. 2005 Nov;37(11):657-61. doi: 10.1055/s-2005-870574.
Results Reference
background
PubMed Identifier
19996061
Citation
Chai W, Wang W, Liu J, Barrett EJ, Carey RM, Cao W, Liu Z. Angiotensin II type 1 and type 2 receptors regulate basal skeletal muscle microvascular volume and glucose use. Hypertension. 2010 Feb;55(2):523-30. doi: 10.1161/HYPERTENSIONAHA.109.145409. Epub 2009 Dec 7.
Results Reference
background
PubMed Identifier
20978231
Citation
Wang N, Ko SH, Chai W, Li G, Barrett EJ, Tao L, Cao W, Liu Z. Resveratrol recruits rat muscle microvasculature via a nitric oxide-dependent mechanism that is blocked by TNFalpha. Am J Physiol Endocrinol Metab. 2011 Jan;300(1):E195-201. doi: 10.1152/ajpendo.00414.2010. Epub 2010 Oct 26.
Results Reference
background
PubMed Identifier
24711523
Citation
Fu Z, Zhao L, Aylor KW, Carey RM, Barrett EJ, Liu Z. Angiotensin-(1-7) recruits muscle microvasculature and enhances insulin's metabolic action via mas receptor. Hypertension. 2014 Jun;63(6):1219-27. doi: 10.1161/HYPERTENSIONAHA.113.03025. Epub 2014 Apr 7.
Results Reference
background
PubMed Identifier
20380649
Citation
Nalysnyk L, Hernandez-Medina M, Krishnarajah G. Glycaemic variability and complications in patients with diabetes mellitus: evidence from a systematic review of the literature. Diabetes Obes Metab. 2010 Apr;12(4):288-98. doi: 10.1111/j.1463-1326.2009.01160.x.
Results Reference
background

Learn more about this trial

Effects of Empagliflozin on Cardiac Microvasculature and Insulin Sensitivity in Subjects With Type 2 Diabetes

We'll reach out to this number within 24 hrs