This study aims to investigate the potential beneficial effects on the kidney of a new medication called Dapagliflozin in type 2 diabetic patients.

• Register: EUCTR
• Last refreshed on: 30 April 2019
• Main ID: EUCTR2013-004042-42-GB
• Date of registration: 14/07/2014
• Prospective Registration: No
• Primary sponsor: King’s College London
• Public title: This study aims to investigate the potential beneficial effects on the kidney of a new medication called Dapagliflozin in type 2 diabetic patients.
• Scientific title: A study to investigate the potential renoprotective role of sodium-glucose transporter-2 (SGLT-2) antagonist Dapagliflozin in Type 2 diabetic patients with diabetic nephropathy - Dapagliflozin in type 2 diabetic nephropathy (DEER)
• Date of first enrolment: 19/06/2014
• Target sample size: 40
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-004042-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

United Kingdom

Contacts

• Name: Dr Janaka Karalliedde
• Affiliation: King's College London

• Name: Dr Janaka Karalliedde
• Affiliation: King's College London

Key inclusion & exclusion 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:
- Patients with impaired renal function (eGFR<60 ml/min);
- Patients with recent (6 months) history of cardiovascular or cerebrovascular disease event;
- Patients on thiazolidinediones (e.g. Pioglitazone);
- Patients who have started drugs which could affect sodium balance (e.g. diuretics, non steroidal anti-inflammatory drugs (NSAID), cyclo-oxygenase (Cox) 2 inhibitors, beta blockers or Calcium channel antagonists) within the previous month;
- Patients with uncontrolled hypertension defined as systolic blood pressure and diastolic blood pressure greater than 160 and 100 mmHg respectively;
- Pregnancy and lactating females
- Pre-menopausal female patients not using contraception;
- Patients with very poorly controlled diabetes defined as HbA1c >12%;
- 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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02]

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

Intervention(s)

Trade Name: Dapagliflozin
Product Name: Dapagliflozin
Pharmaceutical Form: Coated tablet

Product Name: Ramipril
Pharmaceutical Form: Capsule
INN or Proposed INN: RAMIPRIL
CAS Number: 87333-19-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

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.

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 compared to Ramipril only

Timepoint(s) of evaluation of this end point: 24 weeks after treatment with Dapagliflozin and Ramipril compared to Ramipril only.

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)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 24 weeks after treatment with Dapagliflozin and Ramipril compared to Ramipril only.

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)

Secondary ID(s)

DEER

Source(s) of Monetary Support

Astra Zeneca UK Limited

Secondary Sponsor(s)

Guy's and St Thomas NHS Foundation Trust

Ethics review

Status: Approved
Approval date:
Contact: