Assessment of Safety and Efficacy of SGLT2is Among LN Patients

Study Overview
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Brief Summary
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The aim of this study is to assess the safety and efficacy of SGLT2is among LN patients.

Detailed Description
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SLE is a chronic debilitating autoimmune disorder that involves multiple organ systems either simultaneously or sequentially with relapsing and remitting course. The word 'Lupus' is a Latin term which means wolf. Lupus nephritis (LN) is one of the common complications in patients with SLE and influences overall outcome of these patients. About two-thirds of patients with SLE have renal disease at some stage which is a leading cause of mortality in these patients. Manifestations of LN vary from asymptomatic urinary abnormalities to rapidly progressive crescentic glomerulonephritis to end-stage renal disease (ESRD). Recently, metabolic modulation approach has become a hot spot in the management of SLE. Increased glucose metabolism in immune cells has been reported in patients with SLE. Repurposing metformin, an old anti diabetic drug, has the potential to reduce the risk of lupus flare in randomized controlled trials. A recent crossover study implied that peroxisome proliferator-activated receptor-gamma agonists might decrease cardiovascular risk in patients with SLE. Dapagliflozin, SGLT2i, is a new therapy for type 2 diabetes. The Dapagliflozin mode of action is to reduce glucose reabsorption in the epithelial cells of the proximal renal tubule of the kidney, which results in decreased blood glucose and glycated hemoglobin levels. Strikingly, four cardiovascular outcome trials demonstrated that treatment with SGLT2is (empagliflozin, canagliflozin and dapagliflozin) in patients with type 2 diabetes had prominent effects on slowing the decline rate of eGFR and decreasing albuminuria, as well as a significant reduction in cardiovascular events. Furthermore, the nephroprotective efficacy of SGLT2is was extended to non-diabetic CKD, such as IgA nephropathy. The net gain of SGLT2 inhibition is to reduce renal workload and to modulate weight loss and blood pressure. The paradigm for CKD and congestive heart failure management has been shifted accordingly Interestingly, all researchers have reported that SGLT2is could block lipopolysaccharide-induced and NLRP3-mediated inflammatory responses and regulate macrophage polarization via interplay with mammalian target of rapamycin (mTOR) and AMP-activated protein kinase pathway thereby, SGLT2is might further contribute to reducing inflammation, modulating endothelial dysfunction and decelerating atherosclerosis which are all relevant to the pathophysiology of SLE. Here, the investigators initiated this study aiming to assess the safety and efficacy of dapagliflozin among patients with LN.

Official Title
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Assessment of Safety and Efficacy of Sodium Glucose Co-transporter 2 Inhibitors Among Lupus Nephritis Patients

Conditions
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Lupus Nephritis

Intervention / Treatment
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* Drug: Dapagliflozin 10mg Tab orally once daily


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged more than 18 year. Patients with confirmed SLE according to EULAR/ACR classification criteria. Patients with LN ( persistent proteinuria > 2 gm per day or greater than 3+ by dipstick, and/or cellular casts including red cell, hemoglobin, granular, tubular or mixed & active urinary sediment (>5 RBC/hpf, >5 WBC/hpf in the absence of infection, or cellular casts limited to RBC or WBC casts ) Patient with e GFR > 25 ml/min/1.73m2 by CKD-EPI equation. Exclusion Criteria: Patients with an allergy or intolerance to Dapagliflozin or any prior SGLT2i exposure within 1 month before screening. Medical history of chronic disease (Severe respiratory distress, gastrointestinal tract lesions & chronic liver disease) Patients with recurrent genitourinary infections. Patient with proteinuria < 2gm. Patient who show response to immune therapy in proteinuria reduction > 50%. Patient with Lupus in induction phase. Patient on steroids > 30 mg daily dose. Patients with diabetes mellitus. Patients with severe infection requiring antibiotics within 1 month before screening. Patients with malignant diseases. Pregnant or breast-feeding women. Patients with eGFR < 25 ml/min/1.73m2 or undergoing dialysis therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug as Dapagliflozin 10 mg orally for 6 months is given<br>25 lupus nephritis patients will receive SGLT2is as dapagliflozin 10mg beside there usual treatment of lupus for 6 months | Drug: Dapagliflozin 10mg Tab orally once daily<br>* Sodium glucose co-transporter 2 inhibitors<br>* Other names: Empagliflozin 10 mg tab orally once daily;|
| No Intervention: On there conventional lupus nephritis treatment<br>25 lupus nephritis patients didn't receive SGLT2i and continue on their conventional lupus nephritis treatment | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal Function Tests: | Measurement of serum urea level in mg/dl at 3 month's interval, that is, at 0, 3 and 6 months. Measurement of serum creatinine level in mg/dl at 3 month's interval, that is, at 0, 3 and 6 months. Measurement of serum uric acid level in mg/dl at 3 month's interval, that is, at 0, 3 and 6 months. | 6 months |