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Diabetes Mellitus, Type 2Phase 4ADDENDANCT02919345

Assessment of Dapagliflozin Effect on Diabetic Endothelial Dysfunction of Brachial Artery

A Phase 4 study testing Dapagliflozin 10 mg and Glibenclamide 5 mg in people with Diabetes Mellitus, Type 2 and Coronary Artery Disease, run by University of Campinas, Brazil at 1 site in Brazil.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Background Endothelial dysfunction is one of the early events in atherosclerotic plaque development. It is characterized by an increased ratio of substances with vasoconstrictive, pro-thrombotic, and proliferative properties over substances with vasolidatory, antithrombogenic and antimitogenic properties. Read more about this study

Who is it for?
Ages 40 to 70 years
What is being tested?
Dapagliflozin 10 mg and Glibenclamide 5 mg
Could I receive a placebo?
No, everyone receives an active treatment
How many people
98 participants
Where
1 siteBrazil
Study dates
Jan 2017to Mar 2019
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 40 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • chronic coronary artery disease as shown by angiogram or subclinical artery disease diagnosed by the presence of carotid atherosclerotic plaque or carotid Intima-Media Thickness (cIMT) ≥ 1mm;
  • T2DM using up to two oral hypoglycemic agents;
  • inadequate glycemic control (HbA1c ≥ 7%);

Who cannot join

  • HbA1c > 9%;
  • contraindications to metformin use (Cr Clearance <60 ml/min, Cr> 1.5 mg/dL in men and> 1.4 mg/dl in women, liver failure - AST or ALT> 3x upper normal limit or other conditions that might increase the risk of lactic acidosis);
  • at the time of randomization, patient who is not on metformin XR 1500 mg/day monotherapy for at least 12 weeks;
  • patients who spend more than 16 weeks to adjust metformin before randomization;
  • BP ≥ 140 x 90 after 16 weeks of anti-hypertensive medication adjustment;
  • hospitalization for unstable angina or acute myocardial infarction within 2 months prior to enrolment;
Show all 21Show fewer
  • acute stroke or transient ischemic attack (TIA) within two months prior to enrolment;
  • less than two months post coronary artery revascularization;
  • patients with FMD <2% at the time of randomization;
  • triglycerides > 500 mg/dL;
  • known allergy to any of the study drugs;
  • patients with severe coronary artery disease and heart failure;
  • systemic vasculitis;
  • conditions that lead to systemic inflammation;
  • patients using rosiglitazone;
  • polyuria, polydipsia, weight loss, or others clinical signs of volume depletion;
  • those who refuse to participate or sign the Statement of Informed Consent;
  • (xviii) pregnancy or women during reproductive age;
  • breastfeeding women;
  • history of gastrointestinal disorders that may interfere with the absorption of study medication;
  • patients who are participating in other clinical studies or whose participation ended less than six months ago.

Trial locations and contacts

1 site in 1 country.

Brazil1 site

  • State University of Campinas

    Campinas, São Paulo, 13083-887

Other trials in Brazil

About this study

Official title: Comparative Study of Dapagliflozin Versus Glibenclamide Effect on Endothelial Function of Coronary Artery Disease Patients

Background Endothelial dysfunction is one of the early events in atherosclerotic plaque development. It is characterized by an increased ratio of substances with vasoconstrictive, pro-thrombotic, and proliferative properties over substances with vasolidatory, antithrombogenic and antimitogenic properties. Endothelial dysfunction is also associated with high-risk patients with coronary artery disease. Hyperglycemia, obesity, hypertension and fat mass also impair the endothelium by increasing the expression of cytokines, inflammatory markers and vascular markers.

Hypothesis Administration of dapagliflozin in addition to metformin background with clinical or subclinical cardiovascular atherosclerotic disease improves endothelial function when compared to those using glibenclamide in addition to metformin.

Read more

Objectives Evaluate the effect of dapagliflozin vs glibenclamide on a metformin background on endothelial function in patients with clinical or subclinical cardiovascular atherosclerotic disease and poorly controlled diabetes.

Enpoints Prymary Change in flow mediated dilation (FMD) and its related endpoint (FMD post reperfusion lesion) between the randomization visit and over 12 weeks of treatment.

Secondary Change in plasma nitric oxide, isoprostane, ICAM-1, VCAM-1, ET-1, leptin, adiponectin, C-reactive protein, TNF- α, interleukin-6, interleukin-2, weight and body composition (% of fat mass and % free fat mass) at the randomization visit and over 12 weeks of treatment.

3

Design Randomized, parallel-group, comparative, prospective clinical study. The study is divided in two phases: Run-in and Randomization. In the former phase, which must have the maximum period of 16 weeks, patients will visit the outpatient to adjust metformin and blood pressure medications. After run-in phase, patients that fulfill inclusion criteria will perform an ambulatory blood pressure monitoring (ABPM) in order to asses BP; body composition will be assessed by dual x-ray absorptiometry (DXA); endothelial function as assessed by flow mediated dilation and vascular cytokines. Patients will by randomized to dapagliflozin or glibenclamide on a metformin background. After 12 weeks, the ABPM, DXA and endothelial function will be assessed.

Being tested
Dapagliflozin 10 mg, Glibenclamide 5 mg
Keywords
Dapagliflozin, Glibenclamide, Endothelial Function, Vascular Endothelial Cells, Flow Mediated Dilation
Medical subject headings
Diabetes Mellitus, Type 2, Coronary Artery Disease, Carotid Artery Diseases

What participants receive

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

  • Dapagliflozin 10 mgDrug

    Also called Farxiga

    Dapagliflozin 10 mg in addition to Metformin 1500 mg/day

  • Glibenclamide 5 mgDrug

    Also called Daonil, Glyburide

    Glibenclamide 5 mg in addition to Metformin 1500 mg/day

Study groups in NCT02919345
Study groupRoleWhat they receive
DapagliflozinExperimentalDapagliflozin 10 mg in addition to Metformin 1500 mg
Receives: Drug: Dapagliflozin 10 mg
GlibenclamideActive comparatorGlibenclamide 5mg in addition to Metformin 1500 mg
Receives: Drug: Glibenclamide 5 mg

What is being measured

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

  1. Change in flow mediated dilation (FMD) and its related endpoint (FMD post reperfusion lesion)

    Measured: 12 weeks

Secondary outcomes (15)

  1. Change in plasma nitric oxide

    Measured: 12 weeks

  2. Change in plasma isoprostane

    Measured: 12 weeks

  3. Change in plasma nitric oxide after reperfusion injury.

    Measured: 12 weeks

  4. Change in plasma isoprostane after reperfusion injury.

    Measured: 12 weeks

  5. Change in plasma Intercellular Adhesion Molecule 1(ICAM-1)

    Measured: 12 weeks

  6. Change in plasma Vascular Cell Adhesion Molecule 1 (VCAM-1)

    Measured: 12 weeks

  7. Change in plasma Endothelin-1 (ET-1)

    Measured: 12 weeks

  8. Change in plasma Leptin

    Measured: 12 weeks

  9. Change in plasma Adiponectin

    Measured: 12 weeks

  10. Change in plasma C-reactive protein (CRP)

    Measured: 12 weeks

  11. Change in plasma Tumor Necrosis Factor alpha (TNF-α)

    Measured: 12 weeks

  12. Change in plasma interleukin-6

    Measured: 12 weeks

  13. Change in plasma interleukin-2

    Measured: 12 weeks

  14. Change in weight

    Measured: 12 weeks

  15. Change in body composition (% of fat mass and % free fat mass)

    Measured: 12 weeks

Timeline

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

  1. First posted29 Sep 2016 (estimated)
  2. Study startJan 2017
  3. Primary completionDec 2018
  4. Study completionMar 2019

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
None (open label)
Enrolment
98 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02919345
Sponsor's protocol ID
001
Acronym
ADDENDA
Status last verified
Mar 2023
First submitted
28 Sep 2016
Last updated
10 Mar 2023
Results posted
No
Data monitoring committee
No
Individual data sharing
Yes

Publications

  • Kimura-Medorima ST, Oliveira DC, Breder I, Wolf VLW, Soares AAS, Barreto J, Munhoz DB, Cunha JS, Bonilha I, de Carvalho LSF, Coelho-Filho OR, Matos-Souza JR, Moura FA, Nadruz W, Quinaglia T, Sposito AC. Dapagliflozin-induced integrated improvements in left ventricular diastole, endothelial function, and arterial load: a randomized clinical trial. Cardiovasc Diabetol. 2026 Mar 26;25(1):140. doi: 10.1186/s12933-026-03142-y.

    PubMed 41888924

  • Cintra RMR, Soares AAS, Breder I, Munhoz DB, Barreto J, Kimura-Medorima ST, Cavalcante P, Zanchetta R, Breder JC, Moreira C, Virginio VW, Bonilha I, Lima-Junior JC, Coelho-Filho OR, Wolf VLW, Guerra-Junior G, Oliveira DC, Haeitmann R, Fernandes VHR, Nadruz W, Chaves FRP, Arieta CEL, Quinaglia T, Sposito AC; ADDENDA-BHS2 trial investigators. Assessment of dapagliflozin effect on diabetic endothelial dysfunction of brachial artery (ADDENDA-BHS2 trial): rationale, design, and baseline characteristics of a randomized controlled trial. Diabetol Metab Syndr. 2019 Jul 31;11:62. doi: 10.1186/s13098-019-0457-3. eCollection 2019.

    PubMed 31384310

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Dapagliflozin 10 mg and Glibenclamide 5 mg in people with Diabetes Mellitus, Type 2 and Coronary Artery Disease, run by University of Campinas, Brazil at 1 site in Brazil.

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 3 inclusion and 21 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: finished, as of the sponsor's last update on 10 Mar 2023. 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 Brazil. 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?

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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Change in flow mediated dilation (FMD) and its related endpoint (FMD post reperfusion lesion) (time frame: 12 weeks). 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 NCT02919345, which also lists 2 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 Mar 2023.

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