NCT04203927

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

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
50

participants targeted

Target at P50-P75 for early_phase_1

Timeline
Completed

Started Feb 2020

Longer than P75 for early_phase_1

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 17, 2019

Completed
1 day until next milestone

First Posted

Study publicly available on registry

December 18, 2019

Completed
2 months until next milestone

Study Start

First participant enrolled

February 1, 2020

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 30, 2023

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

November 30, 2023

Completed
Last Updated

February 10, 2022

Status Verified

February 1, 2022

Enrollment Period

3.7 years

First QC Date

December 17, 2019

Last Update Submit

February 9, 2022

Conditions

Type2 DiabetesInsulin Sensitivity

Outcome Measures

Primary Outcomes (1)

  • Myocardial microvascular perfusion

    Vascular measure of myocardial perfusion

    Between baseline and 12 weeks treatment

Secondary Outcomes (3)

  • 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)

    Between baseline and 12 weeks of treatment.

  • Augmentation Index ( AI)

    Between baseline and 12 weeks of treatment.

  • Pulse Wave Velocity ( PWV)

    Between baseline and 12 weeks of treatment

Study Arms (2)

Empagliflozin + insulin infusion

ACTIVE COMPARATOR

vascular measurements in overnight fasted state and during insulin infusion

Drug: Empagliflozin 25 MG

Empagliflozin + mixed meal

ACTIVE COMPARATOR

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

Drug: Empagliflozin 25 MG

Interventions

Empagliflozin 25 MGDRUG

SGLT-2 inhibitor

Empagliflozin + insulin infusionEmpagliflozin + mixed meal

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22906, United States

RECRUITING

Related Publications (16)

  • 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.

    PMID: 25633683BACKGROUND

  • 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.

    PMID: 29203583BACKGROUND

  • 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.

    PMID: 23459195BACKGROUND

  • 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.

    PMID: 21047922BACKGROUND

  • 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.

    PMID: 15998667BACKGROUND

  • 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.

    PMID: 21617098BACKGROUND

  • 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.

    PMID: 16386091BACKGROUND

  • 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.

    PMID: 28304392BACKGROUND

  • 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.

    PMID: 26981940BACKGROUND

  • 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.

    PMID: 29166232BACKGROUND

  • 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.

    PMID: 27299675BACKGROUND

  • 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.

    PMID: 16308832BACKGROUND

  • 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.

    PMID: 19996061BACKGROUND

  • 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.

    PMID: 20978231BACKGROUND

  • 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.

    PMID: 24711523BACKGROUND

  • 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.

    PMID: 20380649BACKGROUND

MeSH Terms

Conditions

Insulin Resistance

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

HyperinsulinismGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Study Officials

  • Eugene J Barrett, MD PhD

    University of Virginia

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Eugene J Barrett, MD PhD

CONTACT

434-924-1263ejb8x@virginia.edu

Lee Hartline, MEd

CONTACT

434-924-5247lmh9d@virginia.edu

Study Design

Study Type
interventional
Phase
early phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Prinicipal Investigator

Study Record Dates

First Submitted

December 17, 2019

First Posted

December 18, 2019

Study Start

February 1, 2020

Primary Completion

October 30, 2023

Study Completion

November 30, 2023

Last Updated

February 10, 2022

Record last verified: 2022-02

Locations

US(1)