This study aims to demonstrate the hypothesis that treatment with dapagliflozin 10mg lowers in at least 10-20% of measured glomerular filtration rate (mGFR) in non-diabetic obese patients with glomerular hyperfiltration.
Conditions
Interventions
Trade Name: Edistride
Product Name: Dapagliflozin
Pharmaceutical Form: Tablet
INN or Proposed INN: Dapagliflozin
CAS Number: 461432-26-8
Other descriptive name: DAPAGLIFLOZIN
Concentration unit: mg mi
Sponsors
Hospital Universitari Germans Trias i Pujol
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Age =18 and =70 years 2) Diagnosis of obesity (body mass index =30 Kg/m²) 3) Diagnosis of measured glomerular hyperfiltration (mGFR = 120mL/min) by clearance of iohexol. 4) Understanding and accepting the clinical trial and willing to sign informed consent 5) Twenty of the 60 subjects included must be on a stable dose of angiotensin converting enzyme inhibitors (ACEI) for at least 4 weeks prior to randomization. 6) Women of Child-Bearing Potential (WOCBP: women who have experienced menarche and who have not undergone successful surgical sterilization -hysterectomy, bilateral tubal ligation, or bilateral oophorectomy- or who are not post-menopausal): must be using an acceptable method of contraception (barrier, hormonal or intra uterine device) to avoid pregnancy throughout the study and for up to 4 weeks after the last dose of study drug in such a manner that the risk of pregnancy is minimized.ç7) WOCBP must have a negative serum or urine pregnancy test result within 0 to 72 hours before the first dose of study drug. 8) Women must not be breast-feeding. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1) Not complying inclusion criteria. 2) Diagnosis of type 1 or type 2 Diabetes Mellitus. 3) History of severe hypersensitivity or contraindications to dapagliflozin. 4) Lactose intolerance or glucose-galactasa malabsorption. 5) Treatment a month prior clinical trial beginning of any oral antidiabetic. 6) Autosomal dominant polycystic kidney disease or autosomal recessive polycystic kidney disease, lupus nephritis, or ANCA-associated vasculitis. 7) Receiving cytotoxic therapy, immunosuppressive therapy, or other immunotherapy for primary or secondary renal disease within 6 months prior to enrolment. 8) History of organ transplantation. 9) History of New York Heart Association (NYHA) class IV of cardiac insufficiency. 10) Miocardial infarction, unstable angina, stroke or transient ischemic attack within 12 weeks prior to enrolment. 11) Any medication, surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of medications including, but not limited to any of the following: - History of active inflammatory bowel disease within the last six months; - Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection; - Gastro-intestinal ulcers and/or gastrointestinal or rectal bleeding within last six months; - Pancreatic injury or pancreatitis within the last six months; - Evidence of hepatic disease as determined by any one of the following: ALT or AST values exceeding 3x ULN at the screening visit, a history of hepatic encephalopathy, a history of esophageal varices, or a history of portocaval shunt. 12) History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during the screening. 13) Active malignancy aside from treated squamous cell or basal cell carcinoma of the skin. 14) History of > 2 urinary infections within the last year. 15) Pregnancy or breastfeeding. 16) Participation in any clinical investigation within 3 months prior to initial dosing. 17) History of noncompliance to medical regimens or unwillingness to comply with the study protocol. 18) Any surgical or medical condition, which in the opinion of the investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study. 19) Treatment with antidiabetic drugs, surgery, aggressive diet regimen or significant increase of physical exercise leading to unstable body weight. 19) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and up to 4 weeks after the last dose of study drug. 20) Iodized contrast allergy During the clinical trial, the treatment with concomitant non-steroidal anti-inflammatory drugs (NSAIDs) will be contraindicated, due to the risk of acute renal failure as a consequence of an excessive decrease in renal perfusion.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of dapagliflozin on mGFR in non-diabetic obese patients with glomerular hyperfiltration.;Secondary Objective: Moreover, we will study the effect of dapagliflozin on blood pressure, weight, abdominal, proteinuria, hepatic esteatosis, aric ucid, HbA1c, fasting blood glycemia, insulin resistence, aldosterone, renin, angiotensin II and urinary biomarkers.;Primary end point(s): Decrease in at least 10-20% of measured glomerular filtration rate (mGFR) in non-diabetic obese patients with glomerular hyperfiltration after treatment with dapagliflozin 10mg for 6 weeks relative to placebo (Time Frame: week 0, 6).;Timepoint(s) of evaluation of this end point: Follow-up of 6 weeks. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Maintenance of the decrease in mGFR after 24 weeks of treatment with dapagliflozin. - Comparison of the effect over mGFR between treatment with dapagliflozin 10mg, dapagliflozin 10mg + angiotensin-converting enzyme inhibitors (ACEI) and placebo (Time Frame week 0, 6, 12, 24). - Effect of dapagliflozin 10mg/d compared to placebo and dapagliflozin 10mg +ACEI on proteinuria measured by quotient mg/g (Time Frame week 0, 6, 12 y 24). - Effect of dapagliflozin 10 mg/d compared to placebo and dapagliflozin 10mg +ACEI on systolic/diastolic blood pressure (Time Frame: week 0, 6, 12, 24). - Effect of dapagliflozin 10 mg/d compared to placebo and dapagliflozin 10mg +ACEI on plasmatic levels of aldosterone, renin and angiotensin II hormones (Time Frame: week 0, 6, 12, 24). - Effect of dapagliflozin 10 mg/d compared to placebo and dapagliflozin 10mg+ACEI on body weight and body mass index (Time Frame: week 0, 6, 12, 24). - Effect of dapagliflozin 10mg/d compared to placebo and dapagliflozin 10mg+ACEI on abdominal perimeter (Time Frame: week 0, 6, 12, 24). - Effect of dapagliflozin 10mg/d compared to placebo and dapagliflozin 10mg+ACEI on hepatic esteatosis (Time Frame: week 0, 24). - Effect of dapagliflozin 10mg/d compared to placebo and dapagliflozin 10mg+ACEI on glycated haemoglobin (HbA1c) (Time Frame: week 0, 12, 24). - Effect of dapagliflozin 10mg/d compared to placebo and dapagliflozin 10mg+ACEI on fasting glycemia (Time Frame: week 0, 6, 12, 24). - Effect of dapagliflozin 10mg/d compared to placebo and dapagliflozin 10mg+ACEI on insulin resistance (Time Frame: week 0, 6, 12, 24). - Effect of dapagliflozin 10mg/d compared to placebo and dapagliflozin 10mg+ACEI on seric uric acid (Time Frame: week 0, 6, 12, 24). - Effect of dapagliflozin 10 mg/d compared to placebo and dapagliflozin 10mg+ACEI on selected neurohormones/ biomarkers (Time Frame: week 0, 12, 24).;Timepoint(s) of evaluation of this end point: A follow up of 24 weeks. | — |
Countries
Spain
Contacts
Public ContactServicio de Nefrología
Hospital Universitari Germans Trias i Pujol
Outcome results
None listed