Effects of Dapagliflozin on Progression of Alport Syndrome

Recently, a series of large clinical trials have confirmed the cardio-renal protective effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors. but few patients with hereditary nephritis were included in these studies. This study is to evaluate the effects of dapagliflozin on slowing kidney disease progression in patients with Alport syndrome.

Study Overview

• Status: Active, not recruiting
• Conditions: Alport Syndrome
• Intervention / Treatment: Drug: Dapagliflozin 10mg Tab

• Study Type: Observational
• Enrollment (Actual): 222

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210016
      • Jinling Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients with Alport syndrome who are at risk for kidney disease progression

Description

Inclusion Criteria:

• Histologic or genetic confirmation of Alport syndrome;
• eGFR ≥ 30 ml/min/1.72m2;
• Proteinuria > 0.5 g/24 h;
• Use of an ACE inhibitor or ARB, dose stable for more than 4 weeks;

Exclusion Criteria:

• Concurrence of other types of kidney disease;
• type 1 or type 2 diabetes;
• use of other types of sodium-glucose cotransporter 2 inhibitors within the month prior to enrollment, or prior allergy to such drugs;
• ACEI combined with ARB, or direct renin inhibitors, aldosterone receptor antagonists;
• Uncontrolled hypertension (blood pressure greater than 160/90 mmHg during screening);
• Patients undergoing renal transplantation or maintenance dialysis treatment;
• Coexist with other serious and/or unstable diseases, such as serious cardiovascular diseases, respiratory diseases, liver diseases or neuropsychiatric diseases;
• Patients who are participating in clinical trials of other drugs;
• Pregnant or lactating women, or patients who do not want to receive contraception.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Dapagliflozin + RAS inhibitor; In addition to ACEI/ARB treatment, patients will receive dapagliflozin 10mg once daily for 24 months.	Drug: Dapagliflozin 10mg Tab; Dapagliflozin 10mg daily plus RAS inhibitor; Other Names: Dapagliflozin
RAS inhibitor only; Patients will continue ACEI/ARB treatment for 24 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of eGFR	The change of eGFR from baseline after 24 months of treatment	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of proteinuria	The change of proteinuria from baseline after 24 months of treatment	24 months
Progression of kidney disease	The incidence of doubling of serum creatinine, a sustained ≥40% eGFR decline from baseline, or end-stage kidney disease after treatment	24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of eGFR in different subgroups	The change of eGFR from baseline in patients with different phenotype -genotype after treatment	24 months
Change of proteinuria in different subgroups	The change of proteinuria from baseline in patients with different phenotype -genotype after treatment	24 months

Collaborators and Investigators

• Sponsor: Nanjing University School of Medicine
• Investigators: Principal Investigator: Yu An, MD, National Clinical Research Center of Kidney Diseases

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: January 16, 2024
• First Submitted That Met QC Criteria: January 17, 2024
• First Posted (Actual): January 26, 2024

Study Record Updates

• Last Update Posted (Estimated): September 5, 2024
• Last Update Submitted That Met QC Criteria: September 1, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease; Urogenital Abnormalities; Congenital Abnormalities; Connective Tissue Diseases; Nephritis; Collagen Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Syndrome; Nephritis, Hereditary; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin
• Other Study ID Numbers: 2023DZKY-094

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No