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Trial record 72 of 228 for:    EDN1

Assessment of Dapagliflozin Effect on Diabetic Endothelial Dysfunction of Brachial Artery (ADDENDA)

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ClinicalTrials.gov Identifier: NCT02919345
Recruitment Status : Completed
First Posted : September 29, 2016
Last Update Posted : March 25, 2019
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Andrei Carvalho Sposito, University of Campinas, Brazil

Brief 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. 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.

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.

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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.


Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 Coronary Artery Disease Carotid Artery Diseases Drug: Dapagliflozin 10 mg Drug: Glibenclamide 5 mg Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 98 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Comparative Study of Dapagliflozin Versus Glibenclamide Effect on Endothelial Function of Coronary Artery Disease Patients
Actual Study Start Date : January 2017
Actual Primary Completion Date : December 2018
Actual Study Completion Date : March 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Dapagliflozin
Dapagliflozin 10 mg in addition to Metformin 1500 mg
Drug: Dapagliflozin 10 mg
Dapagliflozin 10 mg in addition to Metformin 1500 mg/day
Other Name: Farxiga

Active Comparator: Glibenclamide
Glibenclamide 5mg in addition to Metformin 1500 mg
Drug: Glibenclamide 5 mg
Glibenclamide 5 mg in addition to Metformin 1500 mg/day
Other Name: Daonil, Glyburide




Primary Outcome Measures :
  1. Change in flow mediated dilation (FMD) and its related endpoint (FMD post reperfusion lesion) [ Time Frame: 12 weeks ]

Secondary Outcome Measures :
  1. Change in plasma nitric oxide [ Time Frame: 12 weeks ]
  2. Change in plasma isoprostane [ Time Frame: 12 weeks ]
  3. Change in plasma nitric oxide after reperfusion injury. [ Time Frame: 12 weeks ]
  4. Change in plasma isoprostane after reperfusion injury. [ Time Frame: 12 weeks ]
  5. Change in plasma Intercellular Adhesion Molecule 1(ICAM-1) [ Time Frame: 12 weeks ]
  6. Change in plasma Vascular Cell Adhesion Molecule 1 (VCAM-1) [ Time Frame: 12 weeks ]
  7. Change in plasma Endothelin-1 (ET-1) [ Time Frame: 12 weeks ]
  8. Change in plasma Leptin [ Time Frame: 12 weeks ]
  9. Change in plasma Adiponectin [ Time Frame: 12 weeks ]
  10. Change in plasma C-reactive protein (CRP) [ Time Frame: 12 weeks ]
  11. Change in plasma Tumor Necrosis Factor alpha (TNF-α) [ Time Frame: 12 weeks ]
  12. Change in plasma interleukin-6 [ Time Frame: 12 weeks ]
  13. Change in plasma interleukin-2 [ Time Frame: 12 weeks ]
  14. Change in weight [ Time Frame: 12 weeks ]
  15. Change in body composition (% of fat mass and % free fat mass) [ Time Frame: 12 weeks ]

Other Outcome Measures:
  1. Change in Glycated Hemoglobin [ Time Frame: 12 weeks ]
  2. Change in Systolic Blood Pressure [ Time Frame: 12 weeks ]
  3. Change in Mean Arterial Blood Pressure [ Time Frame: 12 weeks ]
  4. Change in Waist Circumference [ Time Frame: 12 weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

(i) 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;

(ii) T2DM using up to two oral hypoglycemic agents;

(iii) inadequate glycemic control (HbA1c ≥ 7%);

Exclusion Criteria:

(i) HbA1c > 9%;

(ii) 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);

(vi) at the time of randomization, patient who is not on metformin XR 1500 mg/day monotherapy for at least 12 weeks;

(vii) patients who spend more than 16 weeks to adjust metformin before randomization;

(viii) BP ≥ 140 x 90 after 16 weeks of anti-hypertensive medication adjustment;

(iii) hospitalization for unstable angina or acute myocardial infarction within 2 months prior to enrolment;

(iv) acute stroke or transient ischemic attack (TIA) within two months prior to enrolment;

(v) less than two months post coronary artery revascularization;

(ix) patients with FMD <2% at the time of randomization;

(x) triglycerides > 500 mg/dL;

(xi) known allergy to any of the study drugs;

(xii) patients with severe coronary artery disease and heart failure;

(xiii) systemic vasculitis;

(xiv) conditions that lead to systemic inflammation;

(xv) patients using rosiglitazone;

(xvi) polyuria, polydipsia, weight loss, or others clinical signs of volume depletion;

(xvii) those who refuse to participate or sign the Statement of Informed Consent;

(xviii) pregnancy or women during reproductive age;

(xix) breastfeeding women;

(xx) history of gastrointestinal disorders that may interfere with the absorption of study medication;

(xxi) patients who are participating in other clinical studies or whose participation ended less than six months ago.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02919345


Locations
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Brazil
State University of Campinas
Campinas, Sao Paulo, Brazil, 13083-887
Sponsors and Collaborators
University of Campinas, Brazil
AstraZeneca

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Andrei Carvalho Sposito, MD, PhD, University of Campinas, Brazil
ClinicalTrials.gov Identifier: NCT02919345     History of Changes
Other Study ID Numbers: 001
First Posted: September 29, 2016    Key Record Dates
Last Update Posted: March 25, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Keywords provided by Andrei Carvalho Sposito, University of Campinas, Brazil:
Dapagliflozin
Glibenclamide
Endothelial Function
Vascular Endothelial Cells
Flow Mediated Dilation
Additional relevant MeSH terms:
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Carotid Artery Diseases
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Diabetes Mellitus, Type 2
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Metformin
2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
Glyburide
Hypoglycemic Agents
Physiological Effects of Drugs
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action