SGLT2 Inhibitors Between Reno Protective Effects and Impact on Bone and Mineral Disease Among Lupus Nephritis Patients

SGLT2 Inhibitors Between Reno Protective Effects and Impact on Bone and Mineral Disease Among Diabetic and Non- Diabetic Lupus Nephritis Patients

The goal of this Randomized, controlled trial in 100 patients with LN with an estimated glomerular filtration rate (eGFR) of 25-75 ml/min/1.73m2. Diagnosis of LN was performed by renal biopsy, and all of the renal biopsies were carried out at urology and nephrology center.

1. The main questions it aims to answer are:

• Assess the role of sodium glucose co transporter 2 inhibitors (SGLT2i) in regression of ongoing kidney and cardiac diseases among diabetic or non-diabetic patients with lupus nephritis (LN) under different immunosuppressive therapies.
• Investigate the impact of SGLT2i on bone and mineral metabolism in these patients.

Participants will be randomized into two groups :

• Study group: will receive SGLT2i as add on drug or replace another drug according to the patient clinical situation, Dapagliflozin 10 mg will be used once daily with or without food.
• Control group: will be maintained on their medication.

Study Overview

• Status: Active, not recruiting
• Conditions: Lupus Nephritis; BMD; SGLT2 INHIBITORS
• Intervention / Treatment: Drug: Dapagliflozin tablet; Drug: placebo

Detailed Description

Study sitting: Nephrology and renal transplant unit at urology and nephrology center in Mansoura University.

Study design and sample size:

Randomized, controlled trial that will include 100 patients with Lupus nephritis (LN) with an estimated glomerular filtration rate of 25-75 ml/min/1.73m2. Diagnosis of LN was performed by renal biopsy, and all of the renal biopsies were carried out at urology and nephrology center.

The patients will be randomized into two groups Study group: will receive SGLT2i as add on drug or replace another drug according to the patient clinical situation, Dapagliflozin 10 mg will be used once daily with or without food.

Control group: will be maintained on their medication.

Study Protocol:

Patients in the study group will treated with dapagliflozin initiated at a total daily dosage of 10 mg once daily.

Methods:

The following data will be gathered and evaluated for all patients:

I-before intervention:

Patients of both groups will be subjected to full history taking including duration of LN and drug history and routine clinical examination including blood pressure and BMI measurements.

Laboratory investigations:

Serum creatinine, Creatinine clearance. 24 hour urine protein, urine protein/creatinine ratio. Urine analysis. HBA1c. hemoglobin (HGB). Uric acid and lipid profile. Lupus serology. immunoreactive parathyroid hormone (iPTH). Vitamin D level. Fibroblast growth factor 23 level. bone turnover markers : bone specific alkaline phosphates propeptides of type 1 procollagen tartrate resistant acid phosphatase 5b sclerostin level

Radiological investigation:

Quantitative computed tomography: to detect bone and mineral density (BMD). Cardiovascular assessment: Echocardiography and vascular calcification incidence (NCCT model) : for detection of coronary calcification.

II-after intervention:

All patients will be evaluated monthly regarding:

Regular measurement of blood pressure each visit.

Laboratory investigations:

Serum creatinine, creatinine clearance. 24 hour proteinuria, protein/creatinine ratio. Fasting, random and postprandial glucose levels. calcineurin inhibitors (CNI) trough level if used. Urine analysis. HGB level. Uric acid, lipid profile. Lupus serology.

All patients will be evaluated every 3 month regarding:

1. iPTH
2. Vitamin D level

All patients will be evaluated at 12 month regarding:

1. Fibroblast growth factor 23 level
2. High resolution quantitative computed tomography.
3. Bone turnover markers.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Mansoura, Egypt, 35511
    • Urology and nephrology center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age of patient is more than 18.
• Patients who are willing to sign informed consent.
• Patients with SLE diagnosed according to EULAR/ACR classification criteria.
• Patients with LN according to renal biopsy.
• Patients with eGFR > 30 ml/min/1.73m2.

Exclusion Criteria:

• With eGFR <30 ml/min per 1.73 m2.
• Who is currently pregnancy or lactation.
• With medical history of chronic disease (chronic liver disease, cancer, severe respiratory distress, gastrointestinal tract lesions).
• Refuse to participate in the study or lost follow up.
• With evidence of urinary obstruction of difficulty in voiding at screening.
• Who are receiving high dose diuretics or combined angiotensin-converting enzyme inhibitor (ACEI) and Angiotensin II receptor blockers (ARBS).
• Who have frequent hypotensive episode or systolic blood pressure <100 mmHg. Active malignancy.
• Active infection including HIV.
• Any medications that may affect or interact with bone metabolism such as calcitonin, , denosumab, estrogen and fluoride during the last 6 months.
• Current or previous organ transplantation, or expected to get a kidney transplant within 12 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: study group; Study group: will receive SGLT2i as add on drug or replace another drug according to the patient clinical situation, Dapagliflozin 10 mg will be used once daily with or without food for one year.	Drug: Dapagliflozin tablet; randomized control trial, study group will receive dapagliflozin tablets
Placebo Comparator: control group; Control group: will receive placebo as add on drug once daily with or without food for one year.	Drug: placebo; randomized control trial, control group will receive placebo tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
effect of dapagliflozin on renal function	Effect of dapagliflozin on eGFR (ml/ min).	1 year
effect of dapagliflozin on kidney function	Effect of dapagliflozin on s.creatinine (mg/dl).	1 year
effect of dapagliflozin on BMD	Effect of dapagliflozin on osteoporosis using Qct	1 year
effect of dapagliflozin on minerals	Effect of dapagliflozin on serum calcium and phosphorus (mg/dl)	1 year
effect of dapagliflozin on Bone	Effect of dapagliflozin on bone turnover markers (ng/dl)	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
effect of dapagliflozin on blood pressure	measuring systolic and diastolic blood pressure mmgh before and after intervention	1 year
effect of dapagliflozin on body weight	assessing body weight in kg before and after intervention	1 year

Collaborators and Investigators

• Sponsor: Mansoura University

Study record dates

Study Major Dates

• Study Start (Actual): October 8, 2022
• Primary Completion (Anticipated): October 8, 2023
• Study Completion (Anticipated): December 8, 2023

Study Registration Dates

• First Submitted: January 10, 2023
• First Submitted That Met QC Criteria: January 19, 2023
• First Posted (Estimate): January 30, 2023

Study Record Updates

• Last Update Posted (Estimate): January 30, 2023
• Last Update Submitted That Met QC Criteria: January 19, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: systemic lupus erythematosus; BMD; SGLT2 INHIBITORS
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Kidney Diseases; Urologic Diseases; Connective Tissue Diseases; Glomerulonephritis; Lupus Erythematosus, Systemic; Nephritis; Lupus Nephritis; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin
• Other Study ID Numbers: MD.21.12.574

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: all individual participant data (IPD) that underlie results in a publication
• IPD Sharing Supporting Information Type: Study Protocol; Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No