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

NCT ID: NCT05704088

Last Updated: 2024-10-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-08
• Study Completion Date: 2024-01-08

Brief Summary

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.

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.

Conditions

SGLT2 INHIBITORS; Lupus Nephritis; BMD

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Dapagliflozin tablet

Intervention Type: DRUG

randomized control trial, study group will receive dapagliflozin tablets

control group

Control group: will receive placebo as add on drug once daily with or without food for one year.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

randomized control trial, control group will receive placebo tablets

Interventions

Dapagliflozin tablet

randomized control trial, study group will receive dapagliflozin tablets

Intervention Type: DRUG

placebo

randomized control trial, control group will receive placebo tablets

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mansoura University

OTHER

Sponsor Role: lead

Responsible Party

Mohamed Hosny

nephrology specialist at urology and nephrology center (principle investigator)

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Urology and Nephrology Center

Al Mansurah, , Egypt

Countries

Egypt

Other Identifiers

MD.21.12.574

Identifier Type: -

Identifier Source: org_study_id