The Effect of Curcumin on the Clinical Outcome of Pediatric Patients With Active Lupus Nephritis

Sponsor

Ain Shams University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05714670

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Pediatric Lupus nephritis which is a sever and common complication to childhood onset systemic lupus erythematous is an aggressive inflammatory process triggered by the deposition of antigen-antibody complex in kidney tissue. The complex stimulates production of multiple immune cells, activating Inflammasome NLRP3 that plays massive role in stimulating various cytokines like IL-6. The inflammation also causes elevation in proteinuria and serum creatinine levels beside other inflammatory markers elevation (CRP )and (ESR). These children are treated with a standard regimen consists of an immunomodulator (mycophenolate mofetil) with strong steroid anti-inflammatory and also hydroxychloroquine is added to the regimen to decrease the intensity of the flares and management of arthritis symptoms. In our study we are introducing a powerful antioxidant and anti-inflammatory drug with nephroprotective benefits which is curcumin capsules. The drug showed success in managing different autoimmune and inflammatory diseases as rheumatoid arthritis and Crohn's disease, it also showed dramatic improvement in lupus nephritis models in previous experimental study. The study primary outcome is will be the composite of the effect of curcumin on Urine protein-to-creatinine ratio and NLPR3 Inflammasome levels in blood. Patients meeting the study inclusion criteria will be educated firmly about the disease details and all information about the drug, then will be randomly assigned to one of two groups, the first group receiving the standard therapy only while the second one receiving the standard therapy beside the curcumin 1000 mg capsules orally daily, a third small group of healthy children as a control for normal inflammasome levels. Patients in the first two groups will undergo baseline evaluation at the beginning of the study including Patients' demographic data, anthropometric measures and medication history. Moreover, collecting patients' medical history which includes Duration of systemic lupus, Duration of lupus nephritis, other organs involvement, past and current medical condition or prescribed and OTC medications. Laboratory Evaluation and renal function assessment will include Inflammasome levels in blood using ELISA technique using Human NLRP3 ELISA Kit, Serum creatinine levels, Protein in urine levels, estimated glomerular filtration rate (eGFR) using Original Schwartz Equations, Inflammatory biomarkers (ESR, CRP), anti-ds DNA, anti-ANA DNA and evaluating Hematuria. Baseline Clinical evaluation includes Blood pressure measurement and Kidney structural damage evaluation via biopsy. Then patients will be followed up monthly for three months for assessing Patient Compliance with the prescribed medication regimens and the study drug, Occurrence of side effect graded using monitoring of side effects scale (MOSES) and checking for Allergic reactions against the drug. After the three months, all patients will be reassessed for all laboratory and clinical evaluations. finally results will be statistically analyzed Statistical analysis will be done using SPSS statistical software package

Condition or Disease	Intervention/Treatment	Phase
Lupus Nephritis SLE Nephritis	Drug: Curcumin Oral Capsule	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

72 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Group I: patients will receive the studied drug orally in addition to their standard treatment for three months. Group II: patients will receive only their standard treatment for three months.Group I: patients will receive the studied drug orally in addition to their standard treatment for three months. Group II: patients will receive only their standard treatment for three months.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

The Effect of Curcumin on the Clinical Outcome of Pediatric Patients With Active Lupus Nephritis

Anticipated Study Start Date :

Feb 1, 2023

Anticipated Primary Completion Date :

Aug 1, 2023

Anticipated Study Completion Date :

Nov 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: standard of care patients will receive oral MMF initial dose of 1200 mg/m2/day, no more than 2000 mg/day, increased to 1800 mg/m2/day, no more than 3000 mg/day, if response is not good + corticosteroid protocols are: intravenous pulse of methylprednisolone (30 mg/kg/dose for three consecutive days, no more than de 1000 mg/dose), followed by oral prednisolone/prednisone (0.5-1.0 mg/kg/day); or high dosage oral prednisone/prednisolone (1-2 mg/kg/day, no more than 60 mg/day) + hydroxychloroquine 4.0-5.5 mg/kg/day
Experimental: Curcumin Oral Capsule group patients will receive oral 1000 mg of curcumin capsules daily in addition to their standard treatment for three months. Standard treatment includes: oral MMF initial dose of 1200 mg/m2/day, no more than 2000 m g/day, increased to 1800 mg/m2/day, no more than 3000 mg/day, if response is not good + corticosteroid protocols are: intravenous pulse of methylprednisolone (30 mg/kg/dose for three consecutive days, no more than de 1000 mg/dose), followed by oral prednisolone/prednisone (0.5-1.0 mg/kg/day); or high dosage oral prednisone/prednisolone (1-2 mg/kg/day, no more than 60 mg/day) + hydroxychloroquine 4.0-5.5 mg/kg/day	Drug: Curcumin Oral Capsule Curcumin 1000 mg Oral Capsule beside the standard of care Other Names: Turmeric

Arm

Intervention/Treatment

No Intervention: standard of care

patients will receive oral MMF initial dose of 1200 mg/m2/day, no more than 2000 mg/day, increased to 1800 mg/m2/day, no more than 3000 mg/day, if response is not good + corticosteroid protocols are: intravenous pulse of methylprednisolone (30 mg/kg/dose for three consecutive days, no more than de 1000 mg/dose), followed by oral prednisolone/prednisone (0.5-1.0 mg/kg/day); or high dosage oral prednisone/prednisolone (1-2 mg/kg/day, no more than 60 mg/day) + hydroxychloroquine 4.0-5.5 mg/kg/day

Experimental: Curcumin Oral Capsule group

patients will receive oral 1000 mg of curcumin capsules daily in addition to their standard treatment for three months. Standard treatment includes: oral MMF initial dose of 1200 mg/m2/day, no more than 2000 m g/day, increased to 1800 mg/m2/day, no more than 3000 mg/day, if response is not good + corticosteroid protocols are: intravenous pulse of methylprednisolone (30 mg/kg/dose for three consecutive days, no more than de 1000 mg/dose), followed by oral prednisolone/prednisone (0.5-1.0 mg/kg/day); or high dosage oral prednisone/prednisolone (1-2 mg/kg/day, no more than 60 mg/day) + hydroxychloroquine 4.0-5.5 mg/kg/day

Drug: Curcumin Oral Capsule

Curcumin 1000 mg Oral Capsule beside the standard of care

Other Names:

Turmeric

Outcome Measures

Primary Outcome Measures

chang is being assessed in Urine protein-to-creatinine ratio from baseline [baseline and week12]
urine sample will be examined for albumin levels and creatinine levels, normal ratio for paediatrics is less than 0.25
change is being assessed in NLPR3 Inflammasome serum levels from baseline [baseline and week12]
serum sample will be examined for NLRP3 inflammasome levels and how it is affected by the tested drug

Secondary Outcome Measures

Erythrocyte sedimentation rate [baseline, week 4, week 8 and week 12]
blood sample is examined for ESR level
C-reactive protein [baseline, week 4, week 8 and week 12]
blood sample is examined for CRP level
Anti-ANA DNA [baseline and week 12]
antinuclear antibody

Eligibility Criteria

Criteria

Ages Eligible for Study:

5 Years to 16 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

1- Lupus nephritis patients both genders aged 16 or younger 2- Biopsy specimens confirmed active lesions or active and chronic lesions defined as classII, III or IV lupus nephritis according to WHO classification 3- Children on standard treatment (mycophenolate mofetil + hydroxychloroquine + steroids)

Exclusion Criteria:

Dialysis or B cell-targeted therapy (including belimumab) within the preceding year
Receipt of CYC induction therapy within 3 months before the start of the trial
Smokers
Previous failures of both MMF and CYC induction therapy,
Estimated glomerular filtration rate (eGFR) of less than 30 ml/min per 1.73 m2 of body surface area.
Patients with other comorbidities