Effect of Dapagliflozin in Non-Diabetic Patients With Nephrotic Syndrome.

July 26, 2023 updated by: Amal A. Elkholy, Ain Shams University

Assessment of the Renoprotective Effect of Dapagliflozin in Non-Diabetic Patients With Nephrotic Syndrome.

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

90

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 Contact

Study Contact Backup

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

Accepts Healthy Volunteers

No

Description

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.

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: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Dapagliflozin group and Standard therapy which include either ACEI or ARB
- The first group (45 patients) will receive Dapagliflozin (Diglifloz) 10 mg orally once daily at any time of day with or without food. Tablets are to be swallowed whole with half a cup of water for 24 weeks and standard therapy which include either angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB).
Drug: Dapagliflozin and Standard therapy (ACEI or ARB).
Dapagliflozin (Diglifloz) 10 mg orally once daily for 24 weeks and the standard therapy (ACEI or ARB).
Other Names:
  • Dapagliflozin (Diglifloz) 10 mg orally once daily and the standard therapy (ACEI or ARB).
Drug: Standard Therapy (ACEI or ARB).
Standard Therapy which include either ACEI or ARB for 24 weeks.
Other Names:
  • Standard Therapy which include either ACEI or ARB.
Active Comparator: Standard therapy which include either ACEI or ARB
- The second group (45 patients); will receive the standard therapy (ACEI or ARB).
Drug: Dapagliflozin and Standard therapy (ACEI or ARB).
Dapagliflozin (Diglifloz) 10 mg orally once daily for 24 weeks and the standard therapy (ACEI or ARB).
Other Names:
  • Dapagliflozin (Diglifloz) 10 mg orally once daily and the standard therapy (ACEI or ARB).
Drug: Standard Therapy (ACEI or ARB).
Standard Therapy which include either ACEI or ARB for 24 weeks.
Other Names:
  • Standard Therapy which include either ACEI or ARB.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessment of the effect of Dapagliflozin on proteinuria.
Time Frame: Change from Baseline UPCR at 6 months
By measuring UPCR.
Change from Baseline UPCR at 6 months
Assessment of the effect of Dapagliflozin on proteinuria.
Time Frame: Change from Baseline Serum Albumin at 6 months
By measuring serum albumin
Change from Baseline Serum Albumin at 6 months
Assessment of the effect of Dapagliflozin on Glomerular Filtration Rate (GFR).
Time Frame: Change from Baseline Serum Creatinine at 6 months
By measuring serum creatinine.
Change from Baseline Serum Creatinine at 6 months
Assessment of the effect of Dapagliflozin on Glomerular Filtration Rate (GFR).
Time Frame: Change from Baseline eGFR at 6 months
By measuring eGFR.
Change from Baseline eGFR at 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessment of the effect of Dapagliflozin on Systolic blood pressure.
Time Frame: Change from Baseline Systolic Blood Pressure at 6 months
By measuring Systolic blood pressure.
Change from Baseline Systolic Blood Pressure at 6 months
Assessment of the effect of Dapagliflozin on Diastolic blood pressure.
Time Frame: Change from Baseline Diastolic Blood Pressure at 6 months
By measuring Diastolic blood pressure.
Change from Baseline Diastolic Blood Pressure at 6 months
Assessment of the effect of Dapagliflozin on uric acid.
Time Frame: Change from Baseline Uric acid at 6 months
By measuring uric acid.
Change from Baseline Uric acid at 6 months
Assessment of the effect of Dapagliflozin on lipid profile.
Time Frame: Change from Baseline lipid profile at 6 months
By measuring lipid profile.
Change from Baseline lipid profile at 6 months

Collaborators and Investigators

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

Sponsor

Ain Shams University

Investigators

  • Study Chair: Nagwa A. Sabri, Professor, Department of Clinical Pharmacy

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Estimated)

August 1, 2023

Primary Completion (Estimated)

January 1, 2024

Study Completion (Estimated)

March 1, 2024

Study Registration Dates

First Submitted

June 19, 2023

First Submitted That Met QC Criteria

July 26, 2023

First Posted (Actual)

August 1, 2023

Study Record Updates

Last Update Posted (Actual)

August 1, 2023

Last Update Submitted That Met QC Criteria

July 26, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Dapagliflozin in NS

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

No

Studies a U.S. FDA-regulated device product

No

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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