Assessment of Dapagliflozin Effect on Diabetic Endothelial Dysfunction of Brachial Artery

Sponsor
University of Campinas, Brazil
Study ID
NCT02919345
Phase
PHASE4
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
40 Years - 70 Years
Healthy Volunteers
Not accepted

Interventions

  • Dapagliflozin 10 mg — DRUG
    Dapagliflozin 10 mg in addition to Metformin 1500 mg/day
  • Glibenclamide 5 mg — DRUG
    Glibenclamide 5 mg in addition to Metformin 1500 mg/day

Study Details

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. 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.

Key Dates

Start date
Jan 31, 2017
Status verified
Mar 2023
Primary completion
Dec 31, 2018
Completion
Mar 31, 2019

Study Design

Enrollment
98 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Dapagliflozin
    Dapagliflozin 10 mg in addition to Metformin 1500 mg
  • Active Comparator: Glibenclamide
    Glibenclamide 5mg in addition to Metformin 1500 mg

Primary Outcome Measure

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

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