Clinical trial NCT06532682: Efficacy of Dapagliflozin in Early Diabetic Nephropathy in Type 1 Diabetes
Official title: Efficacy and Mechanism of Dapagliflozin Combined With Insulin in the Treatment of Early Diabetic Nephropathy in Patients With Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Diabetic Kidney Disease
Type 1 Diabetes
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
First posted: 2024-08-01
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Urinary albumin-to-creatinine ratio
timeFrame: From baseline to 24 weeks
measure: estimated Glomerular Filtration Rate
timeFrame: From baseline to 24 weeks
Secondary outcomes:
measure: 24-hour urine biochemical quantification
timeFrame: From baseline to 24 weeks
measure: HbA1c
timeFrame: From baseline to 24 weeks
measure: Weight
timeFrame: From baseline to 24 weeks
measure: Time in Range
timeFrame: From baseline to 24 weeks
measure: Daily insulin dose
timeFrame: From baseline to 24 weeks
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Nanjing Medical University First Affiliated Hospital
state: Jiangsu
Study officials:
affiliation: Nanjing Medical University First Affiliated Hospital
name: Mei Zhang
role: PRINCIPAL_INVESTIGATOR
References: