Type2 DiabetesEarly Phase 1EJB051NCT04203927
Effects of Empagliflozin on Cardiac Microvasculature and Insulin Sensitivity in Subjects With Type 2 Diabetes
A Early Phase 1 study testing Empagliflozin 25 MG in people with Type2 Diabetes and Insulin Sensitivity, run by University of Virginia at 1 site in United States.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Type2 Diabetes, Insulin Sensitivity
- What is being tested?
- Empagliflozin 25 MG
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2020to 30 Nov 2023
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- • 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
Show all 12Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
University of Virginia
Charlottesville, Virginia, 22906
Eugene Barrett, MD, PhD, 434-924-1175, ejb8x@virginia.edu
Zhenqi Liu, MD, zl3e@virginia.edu
About this study
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
Read the 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
- Conditions
- Type2 Diabetes, Insulin Sensitivity
- Being tested
- Empagliflozin 25 MG
- Medical subject headings
- Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Empagliflozin 25 MGDrug
SGLT-2 inhibitor
| Study group | Role | What they receive |
|---|---|---|
| Empagliflozin + insulin infusion | Active comparator | vascular measurements in overnight fasted state and during insulin infusion Receives: 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) Receives: Drug: Empagliflozin 25 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Myocardial microvascular perfusion
Vascular measure of myocardial perfusion
Measured: 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)
Vascular measure of conduit artery stiffness
Measured: Between baseline and 12 weeks of treatment.
Augmentation Index ( AI)
Measurement of central artery stiffness
Measured: Between baseline and 12 weeks of treatment.
Pulse Wave Velocity ( PWV)
Measurement of central artery stiffness
Measured: Between baseline and 12 weeks of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2019
- Study start1 Feb 2020
- Primary completion30 Oct 2023 (estimated)
- Study completion30 Nov 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for Type2 DiabetesStudies of the same condition, open and under way.
- More trials run by University of VirginiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Eugene Barrett, University of Virginia
- Investigators
- Eugene J Barrett, MD PhD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04203927
- Sponsor's protocol ID
- 21403
- Other IDs
- 1R01HL142250-01A1
- Acronym
- EJB051
- Status last verified
- Feb 2022
- First submitted
- 17 Dec 2019
- Last updated
- 10 Feb 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 25633683Inzucchi 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.
PubMed 29203583Zhao 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.
PubMed 23459195Liu 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.
PubMed 21047922Scognamiglio 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.
PubMed 15998667Chai 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.
PubMed 21617098Kovatchev 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.
PubMed 16386091Kovatchev 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.
PubMed 28304392Zinman 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.
PubMed 26981940Neal 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.
PubMed 29166232Wanner 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.
PubMed 27299675Kolka 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.
PubMed 16308832Chai 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.
PubMed 19996061Wang 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.
PubMed 20978231Fu 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.
PubMed 24711523
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Empagliflozin on Cardiac Microvasculature and Insulin Sensitivity in Subjects With Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT04203927
- Acronym / sponsor ID
- EJB051 / 21403
- Conditions
- Type2 Diabetes, Insulin Sensitivity
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 1 Feb 2020 (actual)
- Primary completion
- 30 Oct 2023 (estimated)
- Study completion
- 30 Nov 2023 (estimated)
- First posted
- 18 Dec 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Empagliflozin + insulin infusion | Active comparator | Drug: Empagliflozin 25 MGvascular measurements in overnight fasted state and during insulin infusion |
| Empagliflozin + mixed meal | Active comparator | Drug: Empagliflozin 25 MGvascular measurements in overnight fasted state and 2 hours after mixed meal 10kcal/kg body weight ( 55% Cho, 30%Fat, 20% Pro) |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (12 listed)
- • Smoking presently or in the past 6 months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Empagliflozin 25 MGSGLT-2 inhibitor | Drug | Empagliflozin + insulin infusion, Empagliflozin + mixed meal |
Primary outcome
Myocardial microvascular perfusion
Time frame: Between baseline and 12 weeks treatment
Vascular measure of myocardial perfusion
3 secondary outcomes
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)
Time frame: Between baseline and 12 weeks of treatment.
Augmentation Index ( AI)
Time frame: Between baseline and 12 weeks of treatment.
Pulse Wave Velocity ( PWV)
Time frame: Between baseline and 12 weeks of treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2022.
- Background: PubMed 25633683Nishimura 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.
- Background: PubMed 29203583Inzucchi 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.
- Background: PubMed 23459195Zhao 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.
- Background: PubMed 21047922Liu 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.
- Background: PubMed 15998667Scognamiglio 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.
- Background: PubMed 21617098Chai 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.
- Background: PubMed 16386091Kovatchev 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.
- Background: PubMed 28304392Kovatchev 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.
- Background: PubMed 26981940Zinman 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.
- Background: PubMed 29166232Neal 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.
- Background: PubMed 27299675Wanner 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.
- Background: PubMed 16308832Kolka 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eugene J Barrett, MD PhD principal investigator
University of Virginia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Empagliflozin 25 MG in people with Type2 Diabetes and Insulin Sensitivity, run by University of Virginia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Eugene J Barrett, MD PhD (434-924-1263, ejb8x@virginia.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Myocardial microvascular perfusion (time frame: Between baseline and 12 weeks treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04203927, which also lists 16 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2022.