Effects of dapagliflozin treatment on urinary proteomic patterns in patients with type 2 diabetes

Phase 1

Conditions: Diabetes type 2 and albuminuria
MedDRA version: 18.1Level: PTClassification code 10067585Term: Type 2 diabetes mellitusSystem Organ Class: 10027433 - Metabolism and nutrition disorders
Therapeutic area: Diseases [C] - Hormonal diseases [C19]

Registration Number: EUCTR2015-000335-32-DK

Lead Sponsor: Steno Diabetes Center

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 40

Inclusion Criteria

Male or female patients >18 years of age with a diagnosis of type 2 diabetes (WHO criteria).
Patients must be on current stable antiglycaemic treatment with oral drugs (OAD) or insulin 4 weeks before start of study drug and throughout study duration.
Patients must be on stable antihypertensive treatment (must include renin-angiotensin system blocking treatment) 4 weeks before start of study drug and throughout study duration.
HbA1c >7.5 %
Urinary albumin creatinine ratio (UACR) > 30 mg/g (in =2 out 3 morning spot urine collections prior to randomisation).
eGFR = 45 ml/min/1.73 m2
Stable RAAS-blocking treatment (more than or equal to 4 weeks prior to visit 0) If not stable at visit 0, screening phase can be prolonged to 4 weeks.

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 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion Criteria

Current treatment with loop diuretics
Current treatment with thiazolidinediones
Current treatment with dapagliflozin or other SGLT2 inhibitor
Ongoing cancer treatment
Patients on hypertension treatment who are is not on stable antihypertensive treatment (must include renin-angiotensin system blocking treatment) 4 weeks before start of study drug and throughout study duration
Severe hepatic insufficiency and/or significant abnormal liver function defined as aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3x ULN
Total bilirubin >2.0 mg/dL (34.2 µmol/L)
Positive serologic evidence of current infectious liver disease including, Hepatitis B surface antigen and antibody and Hepatitis C virus antibody
eGFR: <45 mL/min (calculated by MDRD formula)
History of unstable or rapidly progressing renal disease
Volume depleted patients. Patients at risk for volume depletion due to co-existing conditions or concomitant medications, such as loop diuretics should have careful monitoring of their volume status
Recent Cardiovascular Events in a patient:
1. Acute Coronary Syndrome (ACS) within 2 months prior to enrolment 2.Hospitalization for unstable angina or acute myocardial infarction within 2 months prior to enrolment
3. Acute Stroke or TIA within two months prior to enrolment
4. Less than two months post coronary artery revascularization
Congestive heart failure defined as New York Heart Association (NYHA) class IV, unstable or acute congestive heart failure. Note: eligible patients with congestive heart failure, especially those who are on diuretic therapy, should have careful monitoring of their volume status throughout the study.
Pregnant or breastfeeding patients
Patients who, in the judgement of the investigator, may be at risk for dehydration

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the effect of dapagliflozin treatment on urinary proteomic patterns in patients with type 2 diabetes, microalbuminuria, and eGFR above 60 ml/min/1.73m2;Secondary Objective: To evaluate the effect of dapagliflozin treatment on other biomarkers for:<br>Microcirculation and vascular calcification, inflammation, oxidative stress, tubular function, endithelial dysfunction, kidney function (GFR), albuminuria (UAER) ;Primary end point(s): Change in urinary peptide patterns during treatment dapagliflozin treatment compared to placebo;Timepoint(s) of evaluation of this end point: Change in urinary peptide patterns after the first and second treatment period of 12 weeks each

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Change in global longitudinal strain meassured by ekko, GFR, 24-hour blood pressure, albuminuria, microcirculation, and markers of oxidative stress, tubular function, inflammation, and endithelial dysfunction during active treatment compared to placebo ;Timepoint(s) of evaluation of this end point: Change in 24-hour blood pressure, albuminuria, microcirculation, and markers of oxidative stress, tubular function, inflammation, and endithelial dysfunction before and after the first and second treatment period of 12 weeks each, global longitudinal strain measured by ekko, and GFR only after the first and second treatment period of 12 weeks each.

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