Clinical trial NCT05966818: Effect of Dapagliflozin in Non-Diabetic Patients With Nephrotic Syndrome.
Official title: Assessment of the Renoprotective Effect of Dapagliflozin in Non-Diabetic Patients With Nephrotic Syndrome.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Nephrotic Syndrome
Keywords: Nephrotic Syndrome
SGLT2 inhibitor
dapagliflozin
management
proteinuria
Lead sponsor: Ain Shams University
Sponsor class: OTHER
First posted: 2023-08-01
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study is a Prospective, Randomized, Interventional, Parallel, Open Label study.
Primary purpose: TREATMENT

Brief summary: Dapagliflozin is the first SGLT2 inhibitor to be approved for CKD treatment regardless of diabetes status. Since many etiologies of non-diabetic nephropathy are characterized by intraglomerular hypertension, it was hypothesized that dapagliflozin acutely decreases GFR and proteinuria in patients without diabetes at risk of progressive kidney function loss such as nephrotic patients via a glucose independent hemodynamic mechanism.

The aim of the study is to assess the effect of Dapagliflozin on proteinuria and estimated glomerular filtration rate in non-diabetic patients with nephrotic syndrome in order to slow the decline in kidney function and the progression to ESRD and to prevent the complications of nephrotic syndrome like thrombotic diseases, peritonitis, hyperuricemia, and recurrent infections.

Detailed description: Nephrotic syndrome (NS) is a clinical syndrome defined by massive proteinuria (greater than 40 mg/m2 per hour) responsible for hypoalbuminemia (less than 30 g/L), with resulting hyperlipidemia, edema, and other complications as thrombotic diseases, peritonitis and recurrent infections.

Dapagliflozin is the first SGLT2 inhibitor to be approved for CKD treatment regardless of diabetes status. Since many etiologies of non-diabetic nephropathy are characterized by intra-glomerular hypertension, it was hypothesized that Dapagliflozin decreases GFR and proteinuria in patients without diabetes at risk of progressive kidney function loss via a glucose independent hemodynamic mechanism.

The aim of the study is to assess the effect of Dapagliflozin on proteinuria and estimated glomerular filtration rate in non-diabetic patients with nephrotic syndrome.

The study will include 90 patients with diagnosis of nephrotic syndrome (proteinuria ≥3.5g/24hr, and serum albumin ≤30g/L) and Urine protein/Creatinine Ratio (UPCR) ≥2. Serum creatinine \<3mg/dl (265.2umol/L) and eGFR \>30 ml/min/1.73 m2. They will assigned randomly into 2 groups. Each group will contain 45 patients.

* The first group will receive Dapagliflozin (Diglifloz) 10 mg orally once daily for 24 weeks and the standard therapy (ACEI or ARB).
* The second group will receive the standard therapy (ACEI or ARB).

A. Baseline assessment:

At baseline , the non-diabetic patients with nephrotic syndrome will undergo:

* A detailed medical history,
* Physical examination,
* Blood pressure,
* Complete blood count (CBC),
* Baseline biochemical laboratory tests including: kidney function tests (Urinary protein/creatinine ratio (UPCR), eGFR, serum albumin, serum creatinine, serum uric acid, Blood urea nitrogen (BUN), lipid profile and serum glucose level

B. Follow up assessment:

Patients will be followed up every four weeks during the study period (6 months) by measuring UPCR, eGFR, serum albumin, serum creatinine, Blood urea nitrogen (BUN), blood pressure, uric acid, glucose level, lipid profile and CBC. In between visits, patients will be contacted via phone for monitoring of any side effects.

C. End of study assessment:

After 6 months, the previous biochemical tests will be performed such as UPCR, eGFR, serum albumin, serum creatinine, Blood urea nitrogen (BUN), blood pressure, uric acid, glucose level, lipid profile and CBC to measure changes from the baseline.

Eligibility criteria: Inclusion Criteria:

* Age ≥18 and ≤60 years.
* Patients with diagnosis of nephrotic syndrome (proteinuria ≥3.5g/24hr, and serum albumin ≤30g/L) and Urine protein/Creatinine Ratio (UPCR) ≥2.
* Serum creatinine \<3mg/dl (265.2umol/L) and eGFR \>30 ml/min/1.73 m2.
* Pathological diagnosis with membranous nephropathy (MN) or focal segmental glomerulosclerosis (FSGS).
* Absence of any contraindication to dapagliflozin (eGFR less than 30).
* On a stable dose of an ACEI or ARB for at least 4 weeks prior to randomization or Initiation of ACEI or ARB.
* Agreed to participate and sign written informed consent.

Exclusion Criteria:

* Diagnosis of type 1 or type 2 diabetes mellitus.
* Autosomal dominant polycystic kidney disease or autosomal recessive polycystic kidney disease or lupus nephritis.
* Active malignancy aside from treated squamous cell or basal cell carcinoma of the skin.
* History of severe hypersensitivity or contraindications to dapagliflozin.
* History of repeated urinary tract infection or fungal infection.
* Patients with Hemodynamic instability or Hypotension.
* History of noncompliance to medical regimens or unwillingness to comply with the study protocol.
* Pregnancy or breastfeeding.

Primary outcomes:
measure: Assessment of the effect of Dapagliflozin on proteinuria.
timeFrame: Change from Baseline UPCR at 6 months
measure: Assessment of the effect of Dapagliflozin on proteinuria.
timeFrame: Change from Baseline Serum Albumin at 6 months
measure: Assessment of the effect of Dapagliflozin on Glomerular Filtration Rate (GFR).
timeFrame: Change from Baseline Serum Creatinine at 6 months
measure: Assessment of the effect of Dapagliflozin on Glomerular Filtration Rate (GFR).
timeFrame: Change from Baseline eGFR at 6 months
Secondary outcomes:
measure: Assessment of the effect of Dapagliflozin on Systolic blood pressure.
timeFrame: Change from Baseline Systolic Blood Pressure at 6 months
measure: Assessment of the effect of Dapagliflozin on Diastolic blood pressure.
timeFrame: Change from Baseline Diastolic Blood Pressure at 6 months
measure: Assessment of the effect of Dapagliflozin on uric acid.
timeFrame: Change from Baseline Uric acid at 6 months
measure: Assessment of the effect of Dapagliflozin on lipid profile.
timeFrame: Change from Baseline lipid profile at 6 months
Other outcomes:
Locations:
Study officials:
affiliation: Department of Clinical Pharmacy
name: Nagwa A. Sabri, Professor
role: STUDY_CHAIR
References:
citation: Hussein N, Abdelrahman F, Khedr A, Aref H, Halawa MR, ELSharkawy M. Value of Sodium-Glucose Co-Transporter 2 Inhibitor Versus Traditional Medication in Microalbuminuric Diabetic Patients. Curr Diabetes Rev. 2021;17(6):e101120187809. doi: 10.2174/1573399816999201110194413.
citation: Tapia C, Bashir K. Nephrotic Syndrome. 2023 May 29. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK470444/
citation: Wang CS, Greenbaum LA. Nephrotic Syndrome. Pediatr Clin North Am. 2019 Feb;66(1):73-85. doi: 10.1016/j.pcl.2018.08.006.
citation: Heerspink HJL, Stefansson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, Mann JFE, McMurray JJV, Lindberg M, Rossing P, Sjostrom CD, Toto RD, Langkilde AM, Wheeler DC; DAPA-CKD Trial Committees and Investigators. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020 Oct 8;383(15):1436-1446. doi: 10.1056/NEJMoa2024816. Epub 2020 Sep 24.