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Diabetes Mellitus, Type 2Phase 4DAPAMICRONCT05392959

Effect of the Antidiabetic Drug Dapagliflozin on the Coronary Macrovascular and Microvascular Function in Type 2 Diabetic Patients

A Phase 4 study testing Dapagliflozin 10 mg Tab in people with Diabetes Mellitus, Type 2, run by Centre Hospitalier Universitaire Saint Pierre at 1 site in Belgium.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

Cardiovascular events remain a major driver of morbidity and mortality in patients with type 2 diabetes mellitus. Diffuse coronary atherosclerosis, combined with impairment of the microcirculation are frequent even in asymptomatic patients and can lead to unfavourable outcomes. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Diabetes Mellitus, Type 2
What is being tested?
Dapagliflozin 10 mg Tab
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
4 participants
Where
1 siteBelgium
Study dates
6 Jun 2022to 17 Jul 2023
Phase
Phase 4
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • type 2 diabetes mellitus (T2DM) patients presenting with stable angina and a clinical indication for cardiac catheterization
  • T2DM patients with non ST elevation myocardial infarction (NSTEMI) or unstable angina referred for cardiac catheterization
  • Demonstration of coronary lesion(s) with non-significant fractional flow reserve (FFR) values (>0.80), for which revascularisation is deferred
  • Agreement to practice an acceptable method of birth control for women of childbearing potential
  • Signed patient informed consent

Who cannot join

  • Age < 18 years old
  • T2DM patients presenting with ST elevation myocardial infarction (STEMI)
  • Pregnancy or breastfeeding
  • Body mass index ≥45 kg/m2
  • Creatinine clearance ≤45 ml/min/1.73 m2 (as calculated by Modification of Diet in Renal Disease Study (MDRD ) formula for estimated Glomerular filtration rate (GFR))
  • Indication of liver disease, defined by serum levels of alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase above 3 x upper limit of normal during screening or run-in phase
Show all 18Show fewer
  • Uncontrolled hyperglycemia with glucose >240 mg/dL after an overnight fast
  • Stroke, or transient ischemic attack at presentation and up to 2 months prior to informed consent
  • Alcohol or drug abuse within 3 months of informed consent that would interfere with trial participation or any ongoing condition leading to decreased compliance with study procedures or study drug intake
  • Any uncontrolled endocrine disorder except type 2 diabetes
  • Treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent
  • Treatment with anti-obesity drugs 3 months prior to informed consent or any other treatment at time of screening leading to unstable body weight
  • Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years
  • Blood dyscrasias or any disorders causing hemolysis or unstable red blood cells
  • Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption
  • Planned cardiac surgery or angioplasty within 3 months
  • Any clinical condition that would jeopardize patient safety while participating in this clinical trial
  • Life expectancy < 3 years

Trial locations and contacts

1 site in 1 country.

Belgium1 site

  • CHU Saint Pierre

    Brussels, Bruxelles-Capitale, Région de;Brussels Hoofdstedelijk Gewest, 1000

Other trials in Belgium

About this study

Official title: Effect of the Antidiabetic Drug DAPAgliflozin on the Coronary Macrovascular and MICROvascular Function in Type 2 Diabetic Patients

Cardiovascular events remain a major driver of morbidity and mortality in patients with type 2 diabetes mellitus. Diffuse coronary atherosclerosis, combined with impairment of the microcirculation are frequent even in asymptomatic patients and can lead to unfavourable outcomes. In recent years, novel classes of antidiabetic drugs have been introduced, with salutary effects on cardiovascular outcomes of diabetic patients. The sodium-glucose linked transporter 2 (SGLT2) inhibitors - gliflozins - bind to the SGLT2 receptors of the proximal tubule of the nephron and cause glycosuria. They have been shown to have favourable cardiovascular effects by reducing deaths from cardiovascular causes in type 2 diabetic patients.

Moreover, dapagliflozin reduces hospitalisation for heart failure in type 2 diabetic heart failure patients with and without reduced ejection fraction and reduces cardiovascular death and all causes mortality in those with reduced ejection fraction.

Read more

It is currently unknown if this is mediated by improvement of coronary physiology both at the level of the epicardial coronary arteries as well as the coronary microcirculation.

The purpose of the study is to explore the impact of dapagliflozin on the coronary and microcirculatory function of type 2 diabetic patients.

Being tested
Dapagliflozin 10 mg Tab, Placebo
Keywords
Diabetes Mellitus, Type 2, Dapagliflozin, Physiological Effects of Drugs, Coronary Artery Disease, Microcirculation, Fraction Flow Reserve, Index of Microcirculatory Resistance, Coronary Flow Reserve
Medical subject headings
Diabetes Mellitus, Type 2, Coronary Artery Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Dapagliflozin 10 mg TabDrug

    Also called Forxiga®

    Dapagliflozin 10 mg per day

  • PlaceboDrug

    Placebo for dapagliflozin film-coated tablets 10 mg

Study groups in NCT05392959
Study groupRoleWhat they receive
Placebo groupPlacebo comparatorThe patient will be treated in standard of care for type 2 diabetic mellitus and will receive a placebo (1 tablet) administered orally daily during 24 weeks
Receives: Drug: Placebo
dapagliflozin groupExperimentalThe patient will be treated in standard of care for type 2 diabetic mellitus and will receive Dapagliflozin 10 mg (1 tablet) administered orally daily during 24 weeks
Receives: Drug: Dapagliflozin 10 mg Tab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. the longitudinal change of the Fractional Flow Reserve (FRR)

    The longitudinal change (Δ) of FFR is defined as the value at follow-up (6 months) minus the value at baseline.

    The complete assessment of the function of the coronary circulation will be performed by using a dedicated pressure and temperature equipped coronary guidewire (PressureWire X by Abbott Vascular) and the Coroventis CoroFlow software platform.

    In the presence of coronary lesions, the degree of percent diameter stenosis will be measured by quantitative coronary angiography and their hemodynamic significance will be evaluated by measuring fractional flow reserve (FFR). According to the guidelines for myocardial revascularisation, only the lesions that have an FFR value equal or less than 0.8 will be treated by coronary angioplasty . In case of angioplasty, FFR will be also measured immediately after successful implantation of the coronary stent.

    Measured: up to 6 months

  2. the longitudinal change of the Coronary flow reserve (CFR)

    The longitudinal change (Δ) of CFR is defined as the value at follow-up (6 months) minus the value at baseline.

    The complete assessment of the function of the coronary circulation will be performed by using a dedicated pressure and temperature equipped coronary guidewire (PressureWire X by Abbott Vascular) and the Coroventis CoroFlow software platform.

    Coronary flow reserve (CFR) will be measured in the vessels of interest, where FFR was measured.

    Measured: up to 6 months

  3. the longitudinal change of the Index of Microvascular Resistance (IMR).

    The longitudinal change (Δ) of IMR is defined as the value at follow-up (6 months) minus the value at baseline.

    The complete assessment of the function of the coronary circulation will be performed by using a dedicated pressure and temperature equipped coronary guidewire (PressureWire X by Abbott Vascular) and the Coroventis CoroFlow software platform.

    The Index of Microvascular Resistance (IMR) will be measured in the vessels of interest, where FFR was measured.

    Measured: up to 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 May 2022
  2. Study start6 Jun 2022
  3. Primary completion17 Jul 2023
  4. Study completion17 Jul 2023

Why it stopped: recruitment too slow

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Care provider
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05392959
Sponsor's protocol ID
B0762021210908
Acronym
DAPAMICRO
Status last verified
Apr 2024
First submitted
23 May 2022
Last updated
26 Apr 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Ferrannini E, Ramos SJ, Salsali A, Tang W, List JF. Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise: a randomized, double-blind, placebo-controlled, phase 3 trial. Diabetes Care. 2010 Oct;33(10):2217-24. doi: 10.2337/dc10-0612. Epub 2010 Jun 21.

    PubMed 20566676

  • Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas A, Wender R, Matthews DR. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015 Jan;38(1):140-9. doi: 10.2337/dc14-2441. No abstract available.

    PubMed 25538310

  • DeFronzo RA, Norton L, Abdul-Ghani M. Renal, metabolic and cardiovascular considerations of SGLT2 inhibition. Nat Rev Nephrol. 2017 Jan;13(1):11-26. doi: 10.1038/nrneph.2016.170. Epub 2016 Dec 12.

    PubMed 27941935

  • Bailey CJ, Gross JL, Pieters A, Bastien A, List JF. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, double-blind, placebo-controlled trial. Lancet. 2010 Jun 26;375(9733):2223-33. doi: 10.1016/S0140-6736(10)60407-2.

    PubMed 20609968

  • Wilding JP, Rajeev SP, DeFronzo RA. Positioning SGLT2 Inhibitors/Incretin-Based Therapies in the Treatment Algorithm. Diabetes Care. 2016 Aug;39 Suppl 2:S154-64. doi: 10.2337/dcS15-3005.

    PubMed 27440828

  • Abdul-Ghani M, Del Prato S, Chilton R, DeFronzo RA. SGLT2 Inhibitors and Cardiovascular Risk: Lessons Learned From the EMPA-REG OUTCOME Study. Diabetes Care. 2016 May;39(5):717-25. doi: 10.2337/dc16-0041.

    PubMed 27208375

  • Zhou H, Wang S, Zhu P, Hu S, Chen Y, Ren J. Empagliflozin rescues diabetic myocardial microvascular injury via AMPK-mediated inhibition of mitochondrial fission. Redox Biol. 2018 May;15:335-346. doi: 10.1016/j.redox.2017.12.019. Epub 2017 Dec 30.

    PubMed 29306791

  • Ott C, Jumar A, Striepe K, Friedrich S, Karg MV, Bramlage P, Schmieder RE. A randomised study of the impact of the SGLT2 inhibitor dapagliflozin on microvascular and macrovascular circulation. Cardiovasc Diabetol. 2017 Feb 23;16(1):26. doi: 10.1186/s12933-017-0510-1.

    PubMed 28231831

  • van Bommel EJM, Muskiet MHA, Tonneijck L, Kramer MHH, Nieuwdorp M, van Raalte DH. SGLT2 Inhibition in the Diabetic Kidney-From Mechanisms to Clinical Outcome. Clin J Am Soc Nephrol. 2017 Apr 3;12(4):700-710. doi: 10.2215/CJN.06080616. Epub 2017 Mar 2.

    PubMed 28254770

  • Scheen AJ. Pharmacodynamics, efficacy and safety of sodium-glucose co-transporter type 2 (SGLT2) inhibitors for the treatment of type 2 diabetes mellitus. Drugs. 2015 Jan;75(1):33-59. doi: 10.1007/s40265-014-0337-y.

    PubMed 25488697

  • Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A, Silverman MG, Zelniker TA, Kuder JF, Murphy SA, Bhatt DL, Leiter LA, McGuire DK, Wilding JPH, Ruff CT, Gause-Nilsson IAM, Fredriksson M, Johansson PA, Langkilde AM, Sabatine MS; DECLARE-TIMI 58 Investigators. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2019 Jan 24;380(4):347-357. doi: 10.1056/NEJMoa1812389. Epub 2018 Nov 10.

    PubMed 30415602

  • Kato ET, Silverman MG, Mosenzon O, Zelniker TA, Cahn A, Furtado RHM, Kuder J, Murphy SA, Bhatt DL, Leiter LA, McGuire DK, Wilding JPH, Bonaca MP, Ruff CT, Desai AS, Goto S, Johansson PA, Gause-Nilsson I, Johanson P, Langkilde AM, Raz I, Sabatine MS, Wiviott SD. Effect of Dapagliflozin on Heart Failure and Mortality in Type 2 Diabetes Mellitus. Circulation. 2019 May 28;139(22):2528-2536. doi: 10.1161/CIRCULATIONAHA.119.040130. Epub 2019 Mar 18.

    PubMed 30882238

  • Kolh P, Windecker S, Alfonso F, Collet JP, Cremer J, Falk V, Filippatos G, Hamm C, Head SJ, Juni P, Kappetein AP, Kastrati A, Knuuti J, Landmesser U, Laufer G, Neumann FJ, Richter DJ, Schauerte P, Sousa Uva M, Stefanini GG, Taggart DP, Torracca L, Valgimigli M, Wijns W, Witkowski A; European Society of Cardiology Committee for Practice Guidelines; Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S; EACTS Clinical Guidelines Committee; Sousa Uva M, Achenbach S, Pepper J, Anyanwu A, Badimon L, Bauersachs J, Baumbach A, Beygui F, Bonaros N, De Carlo M, Deaton C, Dobrev D, Dunning J, Eeckhout E, Gielen S, Hasdai D, Kirchhof P, Luckraz H, Mahrholdt H, Montalescot G, Paparella D, Rastan AJ, Sanmartin M, Sergeant P, Silber S, Tamargo J, ten Berg J, Thiele H, van Geuns RJ, Wagner HO, Wassmann S, Wendler O, Zamorano JL; Task Force on Myocardial Revascularization of the European Society of Cardiology and the European Association for Cardio-Thoracic Surgery; European Association of Percutaneous Cardiovascular Interventions. 2014 ESC/EACTS Guidelines on myocardial revascularization: the Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur J Cardiothorac Surg. 2014 Oct;46(4):517-92. doi: 10.1093/ejcts/ezu366. Epub 2014 Aug 29. No abstract available.

    PubMed 25173601

  • Gould KL, Lipscomb K, Hamilton GW. Physiologic basis for assessing critical coronary stenosis. Instantaneous flow response and regional distribution during coronary hyperemia as measures of coronary flow reserve. Am J Cardiol. 1974 Jan;33(1):87-94. doi: 10.1016/0002-9149(74)90743-7. No abstract available.

    PubMed 4808557

  • Barbato E, Aarnoudse W, Aengevaeren WR, Werner G, Klauss V, Bojara W, Herzfeld I, Oldroyd KG, Pijls NH, De Bruyne B; Week 25 study group. Validation of coronary flow reserve measurements by thermodilution in clinical practice. Eur Heart J. 2004 Feb;25(3):219-23. doi: 10.1016/j.ehj.2003.11.009.

    PubMed 14972422

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Dapagliflozin 10 mg Tab in people with Diabetes Mellitus, Type 2, run by Centre Hospitalier Universitaire Saint Pierre at 1 site in Belgium.

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 18 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: stopped early, as of the sponsor's last update on 26 Apr 2024. 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 Belgium. 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. Some participants in this study may receive a placebo. 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?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: recruitment too slow). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

the longitudinal change of the Fractional Flow Reserve (FRR) (time frame: up to 6 months). The study lists 3 primary outcomes in all. 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 NCT05392959, which also lists 37 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 26 Apr 2024.

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