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Effects of Dapagliflozin Treatment on Urinary Proteomic Patterns in Patients With Type 2 Diabetes (DapKid)

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ClinicalTrials.gov Identifier: NCT02914691
Recruitment Status : Recruiting
First Posted : September 26, 2016
Last Update Posted : September 27, 2016
Sponsor:
Information provided by (Responsible Party):
Peter Rossing, Steno Diabetes Center

Brief Summary:

Background: SGLT2 inhibitors are the first antiglycaemic drugs with a direct renal action. A part from reducing blood glucose, systemic blood pressure and albuminuria are decreased, while natriuresis is increased.

Previous research into urinary peptide patterns (proteomics) has revealed that patients in risk of progressive renal disease display a "risk peptide pattern" in their urine, ahead of decline in renal function. Furthermore a urinary proteome pattern is related to CVD risk.

The long-term impact of dapagliflozin (dapa) treatment on renal parameters is unknown, but long term randomized trials are ongoing. By investigating the impact of dapa treatment on this peptide pattern, it will be determined whether this intervention can improve the urinary proteomic peptide pattern. In addition new knowledge regarding renal processes that the treatment influences is sought.

The impact of treatment of urinary and tubular markers of oxidative stress and function (metabolomics) will be assessed. These markers are thought to represent one of several deleterious pathways involved in the pathology of diabetic renal disease, and here the impact dapa treatment will be investigated. Improvement of these markers of oxidative stress may indicate long-term benefit.

Objective: The primary objective is to assess the impact of three months of treatment with dapa 10 mg once daily or placebo on renal proteomics pattern and other risk markers of diabetic comorbidity.

Design: Double blinded, randomized, placebo-controlled crossover, single center study. Treatment period: 2 x 12 weeks.

Patient population: 40 patients with type 2 diabetes recruited from Steno Diabetes Center in accordance with the study in- and exclusion criteria.

Intervention: Dapa 10 mg daily vs. placebo. Endpoints: Primary outcome: To evaluate the effect of dapa treatment on urinary proteomic patterns in patients with type 2 diabetes, microalbuminuria and eGFR equal to or above 45 ml/min/1.73m2.

Secondary endpoints are the effect of the intervention on other markers for tubular function, inflammation, endothelial dysfunction, microcirculation, kidney function, albuminuria, vasoactive hormones in plasma, and effect on global longitudinal strain as measured by echocardiography.

Timeframe: Randomisation planned from June 2015, inclusion over the following 9 months. Last patient is expected to be completed October 2016. Data analysis completed December 2016, presentation autumn 2017 and publication early 2018.


Condition or disease Intervention/treatment Phase
Type 2 Diabetes Diabetic Nephropathy Drug: Dapagliflozine 10 mg once daily tablet treatment Drug: Placebo identical once daily tablet treatment Phase 4

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Official Title: Effects of Dapagliflozin Treatment on Urinary Proteomic Patterns in Patients With Type 2 Diabetes
Study Start Date : August 2015
Estimated Primary Completion Date : July 2017

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: Active
Dapagliflozin 10 mg once daily tablet treatment
Drug: Dapagliflozine 10 mg once daily tablet treatment
Placebo Comparator: Placebo
Identical once daily tablet treatment
Drug: Placebo identical once daily tablet treatment



Primary Outcome Measures :
  1. Change in Urinary Peptide Patterns (Proteomics) [ Time Frame: Up to 26 weeks ]
    Proteomics will be evaluated at week 0, at crossover week 12 (+/- 1 week), and at end study week 24 (+/- 1 week)



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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02914691


Contacts
Contact: Mie K Eickhoff, MD +4530797028 mecf@steno.dk
Contact: Frederik I Persson, MD, DMSc frip@steno.dk

Locations
Denmark
Steno Diabetes Center Recruiting
Gentofte, Denmark, 2820
Contact: Mie K Eickhoff, MD    +4530797028    mecf@steno.dk   
Sponsors and Collaborators
Peter Rossing

Responsible Party: Peter Rossing, Professor, MD, DMSc, Steno Diabetes Center
ClinicalTrials.gov Identifier: NCT02914691     History of Changes
Other Study ID Numbers: 2015-000335-32
First Posted: September 26, 2016    Key Record Dates
Last Update Posted: September 27, 2016
Last Verified: September 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Peter Rossing, Steno Diabetes Center:
Type 2 diabetes
Diabetic Nephropathy
Proteomics
Albuminuria
SGLT2 inhibitor

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Kidney Diseases
Diabetic Nephropathies
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Urologic Diseases
Diabetes Complications