Diabetic Nephropathy MedDRA version: 20.1 Level: PT Classification code 10061835 Term: Diabetic nephropathy System Organ Class: 10038359 - Renal and urinary disorders MedDRA version: 20.0 Level: PT Classification code 10067585 Term: Type 2 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Trade Name: Dapagliflozin
Product Name: Dapagliflozin
Pharmaceutical Form: Coated tablet
Product Name: Ramipril
Pharmaceutical Form: Ca
Sponsors
King’s College London
Guy's and St Thomas NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Male and female patients aged 35 to 75 years with known diagnosis of type-2 diabetes as per ADA criteria (1) with HbA1c = 7% on monotherapy or combination therapy with approved hypoglycaemic agents (e.g. metformin, sulphonylurea, acarbose, or DPP IV inhibitor, insulin, GLP-1 receptor agonist) - Patients with residual albuminuria (defined as a urine albumin creatinine ratio (ACR) >3 mg/mmol in the preceding 12 months) on maximal tolerated dose of ACE-inhibitor or ARB - preserved renal function [estimated GFR >60 ml/min by 4 variable MDRD equation (23)] - Patients on a stable dose of ACE-inhibitors or ARB in the preceding 3 months. - Written informed consent to participate in the study prior to any study procedures; - Ability to communicate and comply with all study requirements. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: - Patients with impaired renal function (eGFR12%; - Patients with non diabetic renal disease; - Patients with a history of connective tissue disease or inflammatory arthritis; - Recent ( within 3 months) or current use of SGLT2 receptor blocker; - Patients not willing to use appropriate contraception; - Patients on loop diuretics - Recent history of (within 3 years of screening visit) or active malignancy - Patients with New York Heart Association class 3 or 4 cardiac disease - Abnormal Liver function tests defined as ALT or AST levels >3 times the upper limit of normal at screening - History of hereditary glucose-galactose malabsorption or primary renal glucosuria; - History of one or more severe hypoglycaemic episodes within 6 months of screening; (severe hypoglycaemic episodes is as defined by ADA criteria (24). - Previous hypersensitivity to the active substance or to any of the excipients - Patients with an insufficient understanding of the trial - Patients with a history of DKA or at high risk of DKA (T2DM patients with known low C-peptide (<0.25nmol/l), patients with a history of pancreatitis, patients with conditions that lead to restricted food intake or severe dehydration.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To study the potential protective role of Dapagliflozin on renal disease in patients with Type 2 diabetes and diabetic renal disease. We aim to evaluate in this trial if the combination of Dapagliflozin and Ramipril (an established reno-protective drug) significantly reduces microalbuminuria ( a markers of renal damage) as compared to Ramipril alone in patients with type-2 diabetes with preserved renal function and residual albuminuria despite currently available optimal treatments.; Secondary Objective: Changes in the following will be measured - Central aortic blood pressure and central arterial stiffness; Brachial blood pressure; Plasma renin activity, aldosterone, ACE-2 and Angiotensin 1-7/1-9 levels; Total body water and extracellular fluid volumes by bio-impedance; Highly sensitive CRP; HbA1c, fasting c-peptide, glucose; Lipid profile (total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides); Serum electrolytes (sodium, magnesium, potassium), and renal function (serum creatinine, and estimated GFR; Plasma albumin and liver function tests (ALT, ALP GGT); Serum uric acid, serum calcium, serum phosphate, and haemoglobin; Renal tubular markers L-FABP levels and retinol binding protein; 24 hr urine sodium, urine magnesium, urine uric acid, urine calcium, urine phosphate and urine potassium excretion; Vascular cell adhesion molecule-1, Von Willebrand factor, oxidized low density lipoprotein and endothelin-1; Quality of life (EQOL5) ;Primary end point(s): The primary endpoint will be change albuminuria measured by albumin excretion rate (AER); median of three non-consecutive independent urine collections performed within 10 days of 24 weeks' treatment with Dapagliflozin and Ramipril compare | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Changes in the following will be measured - Central aortic blood pressure and central arterial stiffness; Brachial blood pressure; Plasma renin activity, aldosterone, ACE-2 and Angiotensin 1-7/1-9 levels; Total body water and extracellular fluid volumes by bio-impedance; Highly sensitive CRP; HbA1c, fasting c-peptide, glucose; Lipid profile (total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides); Serum electrolytes (sodium, magnesium, potassium), and renal function (serum creatinine, and estimated GFR; Plasma albumin and liver function tests (ALT, ALP GGT); Serum uric acid, serum calcium, serum phosphate, and haemoglobin; Renal tubular markers L-FABP levels and retinol binding protein, soluble Klotho 24 hr urine sodium, urine magnesium, urine uric acid, urine calcium, urine phosphate and urine potassium excretion; Vascular cell adhesion molecule-1, Von Willebrand factor, oxidized low density lipoprotein and endothelin-1; Quality of life (EQOL5) ;Timepoint(s) of evaluation of this end point: 24 weeks after treatment with Dapagliflozin and Ramipril compared to Ramipril only. | — |
Countries
United Kingdom
Contacts
Public ContactDr Janaka Karalliedde
King's College London
Outcome results
None listed