Efficacy of Dapagliflozin in Early Diabetic Nephropathy in Type 1 Diabetes

July 31, 2024 updated by: The First Affiliated Hospital with Nanjing Medical University

Efficacy and Mechanism of Dapagliflozin Combined With Insulin in the Treatment of Early Diabetic Nephropathy in Patients With Type 1 Diabetes

Diabetic kidney disease (DKD) is a leading cause of chronic and end-stage kidney disease, affecting 25-40% of type 1 diabetes (T1D) patients and 5-40% of type 2 diabetes (T2D) patients. Despite standard treatments like ACE inhibitors and ARBs, many patients continue to develop DKD, indicating a need for better kidney protection. This study aims to evaluate the efficacy and safety of dapagliflozin combined with insulin in early DKD patients with T1DM, using ACEi/ARB as standard treatment, to provide new insights into kidney protection and support precision medicine goals.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

This is an open-label, randomized, parallel-group study to evaluate the effects of dapagliflozin on urinary albumin/creatinine ratio (UACR) in participants with early diabetic nephropathy and type 1 diabetes mellitus (T1DM). The primary objective is to assess the changes in UACR and estimated glomerular filtration rate (eGFR) before and after dapagliflozin treatment in these patients. Secondary objectives include observing blood glucose control, weight improvement, and safety evaluation after dapagliflozin treatment.

The study comprises three groups: dapagliflozin 10 mg, dapagliflozin 5 mg, and a standard treatment control, with a 1:1:1 allocation ratio. Participants meeting the inclusion criteria and not meeting any exclusion criteria will enter a 4-8 week lead-in period, during which they will receive the maximum tolerable dose of ACEI/ARB medications, maintain this treatment for at least 4 weeks, and optimize blood glucose control under the guidance of medical professionals while wearing continuous glucose monitoring devices. Starting from baseline, participants will receive either dapagliflozin 5 mg or 10 mg once daily for 24 weeks, while the control group will continue on the maximum tolerable dose of ACEI/ARB medications. Continuous glucose monitoring and regular ketone monitoring will be performed to prevent diabetic ketoacidosis. Follow-up visits will occur approximately 30 days after the last dose of study medication or upon study completion.

The primary efficacy indicators are the mean changes in UACR and eGFR from baseline to week 24. Secondary efficacy indicators include changes in 24-hour urine biochemistry, HbA1c, body weight, continuous glucose monitoring indices, and total daily insulin dose. Safety evaluation indicators include adverse events, serious adverse events, diabetic ketoacidosis, severe hypoglycemia, and urinary or genital infections.

Study Type

Interventional

Enrollment (Actual)

54

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Jiangsu
      • Nanjing, Jiangsu, China, 210000
        • Nanjing Medical University First Affiliated Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age between 18 and 65 years;
  • Diagnosed with type 1 diabetes mellitus with a disease duration of more than 5 years;
  • Glycated hemoglobin (HbA1c) ≤ 7.5% at screening;
  • Diagnosed with diabetic nephropathy;
  • UACR between 30 and 300 and eGFR ≥ 60 ml/min/1.73 m².

Exclusion Criteria:

  • Other types of diabetes;
  • Use of any antidiabetic medications (excluding insulin) within 1 month prior to screening;
  • History of diabetic ketoacidosis within 3 months prior to screening, or a diagnosed episode of diabetic ketoacidosis within the past 1 month;
  • History of poor blood glucose control requiring hospitalization (due to hyperglycemia or hypoglycemia) within 1 month prior to screening;
  • Frequent severe hypoglycemia or unconscious hypoglycemia (more than once requiring medical intervention or emergency care) within 1 month prior to screening;
  • Use of SGLT2 inhibitors or other renal protective medications within 6 months prior to screening;
  • Women who are planning to become pregnant, pregnant, or breastfeeding;
  • Cardiovascular disease (within 6 months prior to screening);
  • Unstable/rapidly progressing renal disease (within 6 months prior to screening), or renal artery stenosis;
  • Major liver disease or malignant tumors (within 5 years prior to screening).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Drug: Dapagliflozin 10 MG + ACE inhibitor
Using ACE inhibitors/ARBs as standard treatment, dapagliflozin is administered at a dose of 10 mg once daily, without food restrictions, for a total treatment duration of 24 weeks.
Drug: dapagliflozin
dapagliflozin 5 MG/10 MG once daily
Other Names:
  • Farxiga
Drug: ACE inhibitor
ACE inhibitor
Experimental: Drug: Dapagliflozin 5 MG + ACE inhibitor
Using ACE inhibitors/ARBs as standard treatment, dapagliflozin is administered at a dose of 5 mg once daily, without food restrictions, for a total treatment duration of 24 weeks.
Drug: dapagliflozin
dapagliflozin 5 MG/10 MG once daily
Other Names:
  • Farxiga
Drug: ACE inhibitor
ACE inhibitor
Active Comparator: Drug: ACE inhibitor
Using ACE inhibitors/ARBs as standard treatment for a total treatment duration of 24 weeks.
Drug: ACE inhibitor
ACE inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Urinary albumin-to-creatinine ratio
Time Frame: From baseline to 24 weeks
Average change from baseline to 24 weeks after treatment
From baseline to 24 weeks
estimated Glomerular Filtration Rate
Time Frame: From baseline to 24 weeks
Average change from baseline to 24 weeks after treatment
From baseline to 24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
24-hour urine biochemical quantification
Time Frame: From baseline to 24 weeks
Average change from baseline to 24 weeks after treatment
From baseline to 24 weeks
HbA1c
Time Frame: From baseline to 24 weeks
Change from baseline to 24 weeks after treatment
From baseline to 24 weeks
Weight
Time Frame: From baseline to 24 weeks
Change from baseline to 24 weeks after treatment
From baseline to 24 weeks
Time in Range
Time Frame: From baseline to 24 weeks
Evaluate blood glucose control through continuous glucose monitoring
From baseline to 24 weeks
Daily insulin dose
Time Frame: From baseline to 24 weeks
Change from baseline to 24 weeks after treatment
From baseline to 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The First Affiliated Hospital with Nanjing Medical University

Investigators

  • Principal Investigator: Mei Zhang, Nanjing Medical University First Affiliated Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2024

Primary Completion (Estimated)

June 30, 2026

Study Completion (Estimated)

October 1, 2026

Study Registration Dates

First Submitted

July 23, 2024

First Submitted That Met QC Criteria

July 31, 2024

First Posted (Actual)

August 1, 2024

Study Record Updates

Last Update Posted (Actual)

August 1, 2024

Last Update Submitted That Met QC Criteria

July 31, 2024

Last Verified

July 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2023-SR-929

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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