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

Primary Purpose

Type 2 Diabetes, Diabetic Nephropathy

Status

Completed

Phase

Phase 4

Locations

Denmark

Study Type

Interventional

Intervention

Dapagliflozine 10 mg once daily tablet treatment

Placebo identical once daily tablet treatment

About this trial

This is an interventional prevention trial for Type 2 Diabetes focused on measuring Type 2 diabetes, Diabetic Nephropathy, Proteomics, Albuminuria, SGLT2 inhibitor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Steno Diabetes Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Active

Placebo

Arm Description

Dapagliflozin 10 mg once daily tablet treatment

Identical once daily tablet treatment

Outcomes

Primary Outcome Measures

Change in Urinary Peptide Patterns (Proteomics)

Proteomics will be evaluated at week 0, at crossover week 12 (+/- 1 week), and at end study week 24 (+/- 1 week)

Secondary Outcome Measures

Full Information

NCT ID

NCT02914691

First Posted

September 9, 2016

Last Updated

September 6, 2018

Sponsor

Peter Rossing

1. Study Identification

Unique Protocol Identification Number

NCT02914691

Brief Title

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

Acronym

DapKid

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2018

Overall Recruitment Status

Completed

Study Start Date

August 2015 (undefined)

Primary Completion Date

July 5, 2017 (Actual)

Study Completion Date

July 5, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Peter Rossing

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 2 Diabetes, Diabetic Nephropathy

Keywords

Type 2 diabetes, Diabetic Nephropathy, Proteomics, Albuminuria, SGLT2 inhibitor

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 4

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

40 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Active

Arm Type

Active Comparator

Arm Description

Dapagliflozin 10 mg once daily tablet treatment

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Identical once daily tablet treatment

Intervention Type

Drug

Intervention Name(s)

Dapagliflozine 10 mg once daily tablet treatment

Intervention Type

Drug

Intervention Name(s)

Placebo identical once daily tablet treatment

Primary Outcome Measure Information:

Title

Change in Urinary Peptide Patterns (Proteomics)

Description

Proteomics will be evaluated at week 0, at crossover week 12 (+/- 1 week), and at end study week 24 (+/- 1 week)

Time Frame

Up to 26 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Facility Information:

Facility Name

Steno Diabetes Center

City

Gentofte

ZIP/Postal Code

2820

Country

Denmark

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

32340841

Citation

Eickhoff MK, Olsen FJ, Frimodt-Moller M, Diaz LJ, Faber J, Jensen MT, Rossing P, Persson F. Effect of dapagliflozin on cardiac function in people with type 2 diabetes and albuminuria - A double blind randomized placebo-controlled crossover trial. J Diabetes Complications. 2020 Jul;34(7):107590. doi: 10.1016/j.jdiacomp.2020.107590. Epub 2020 Apr 18.

Results Reference

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

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