Comparing effect of two different prophylactic Vitamin D dosage on Bone Health in a child with Nephrotic Syndrome (1st Episode)

Phase 2/3

Not yet recruiting

• Conditions: Nephrotic syndrome with unspecified morphologic changes,

• Registration Number: CTRI/2025/03/082823
• Lead Sponsor: AIIMS Bhopal

Brief Summary

Nephrotic syndrome is one among the most common kidney diseases in childhood. It is characterized by edema, massive proteinuria and hypoalbuminemia. The incidence ofidiopathic Nephrotic syndrome is 1·15-16·9 per 100 000 children, varyingby ethnicity and region. Therapy for the initialepisode should comprise of prednisolone at a dose of 60 mg/m2/day (2 mg/kg/day,maximum 60 mg per day) for 6 weeks, followed by 40 mg/m2 (1.5 mg/kg, maximum 40mg) on alternate days for the next 6 weeks, and then discontinued. Thereis a significant risk that children with nephrotic syndrome may experience sideeffects from the high doses of steroids we are administering. Osteoporosis is the most common serious adverse effect of steroid therapyencountered in 30-50% of patients. Mechanism of Corticosteroids induced osteoporosis – Corticosteroids increase the expression of RANK-Land CSF-1 and decrease osteo-protegrin expression by human osteoblastic and stromal cells, which in turn results inincreased osteo-clastogenesis and bone resorption. Corticosteroids promote mature osteoblasts programmed cell death, or apoptosis. Glucocorticoids inhibit the synthesis of type Icollagen, the major component of bone extracellular matrix, with a consequentdecrease in bone matrix available for mineralization. The bone loss predominantly occurs in trabecular bones. Therefore, moresevere osteopenia is seen in vertebrae and ribs. Evaluation of Bone metabolic health using Biochemical Parameters –Calcium, Phosphate, ALP, Vitamin D and Parathormone. Gold standardinvestigation for assessing Bone metabolic health (BMD) – DEXA (Dual EnergyX-ray Absorptiometry),which is advised yearly for patients receiving long-term steroids. In addition, they should also receiveprophylactic calcium and vitamin D supplements. VitaminD deficiency has been identified in many types and stages of nephroticsyndromes, which is exacerbated by continuous biochemical abnormalitiesresulting in a loss of vitamin D binding globulin and proteinuria. The supplementation ofvitamin D is indicated primarily for restoration of the bone health in thesepatients, which is documented in various studies as improvement in biochemicaland radiological parameters of bone health and is recommended byinternational and national guidelines. Reason forsupplementation of Vitamin D and calcium together - Calcium is actively absorbed from the smallintestine in the presence of Vitamin D. Hydroxyapatite crystals are formed by phosphorus and calciumand serve to mineralize and fortify bones. Therefore, for optimal bonemineralization, calcium and vitamin D supplements are required. Prophylacticdoses given in Children at high-risk category is between 400IU – 1000IU per dayalong with calcium as per IAP Guidelines.

Justificationfor the conduct of the study- As there is no universal recommendation forprophylactic supplementation of Vitamin D and calcium in first episode of NS,who is on steroids for < 3 months. But recent studies showed that there issignificant bone loss even in children on steroids for < 3 months. Thisfacilitates need for prophylactic Vitamin D and calcium supplementation inchildren with first episode nephrotic syndrome. Recent guidelines by Indianacademy of Pediatrics suggested to supplement Vitamin D and calcium in childrenwith Nephrotic syndrome (Grade 3 evidence) but dose is not suggested. Very fewstudies are available in literature on need and dose of vitamin D in nephroticsyndrome especially in first episode. As per guidelines Vitamin D and Calciumprophylactic dose ranges from 400IU – 1000 IU & 600 – 800 mg per dayrespectively in high-risk groups. In Previous study, Placebo and Vitamin D(400 IU) was given for children with first episode NS. Dose of 400 IU Vitamin Dshowed a significant change in BMD and Biochemical parameters, but it is notadequate dose to prevent Bone loss. This study is being done to find outefficacy of 600IU vs. 1000IU dosingregimens in preventing steroid induced bone loss in children with first episodeNephrotic syndrome.

Detailed Description

Not available

Study Timeline

• Last Update Posted: 2025-03-19
• Study Start: 2025-03-30

Recruitment & Eligibility

• Status: Not Yet Recruiting
• Sex: All
• Target Recruitment: 56

Inclusion Criteria

All Children between the ages of 1-12 years diagnosed as first episode Nephrotic syndrome.

Exclusion Criteria

• Children with clinical or biochemical evidence of Metabolic bone disease including vitamin D deficiency.
• Children with pre-existing Chronic Liver Disease or Autoimmune Disorder.
• Children with history of prolong steroids intake.
• Children who develop resistance to steroids during the course of treatment.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
1. Compare the proportionate change in Bone Mineral Density (Before and after the standard steroid therapy) in children with new onset nephrotic syndrome receiving vitamin	1. Evaluation of Bone mineral density at the time of diagnosis (first episode nephrotic syndrome) and 4 weeks after completion of Treatment (6 weeks full dose steroids and 6 weeks alternate day steroids) | 2. Evaluation of Biochemical parameters of Mineral bone disease at various time points of study. (Baseline, after 6 weeks of full dose steroids, after 6 weeks of alternate day steroids and after 4 weeks of treatment completion)
1000IU/day.	1. Evaluation of Bone mineral density at the time of diagnosis (first episode nephrotic syndrome) and 4 weeks after completion of Treatment (6 weeks full dose steroids and 6 weeks alternate day steroids) | 2. Evaluation of Biochemical parameters of Mineral bone disease at various time points of study. (Baseline, after 6 weeks of full dose steroids, after 6 weeks of alternate day steroids and after 4 weeks of treatment completion)
D prophylaxis at a dose of 600 IU/day Vs 1000IU/day.	1. Evaluation of Bone mineral density at the time of diagnosis (first episode nephrotic syndrome) and 4 weeks after completion of Treatment (6 weeks full dose steroids and 6 weeks alternate day steroids) | 2. Evaluation of Biochemical parameters of Mineral bone disease at various time points of study. (Baseline, after 6 weeks of full dose steroids, after 6 weeks of alternate day steroids and after 4 weeks of treatment completion)
2. Compare the proportionate change in serum Calcium, Phosphate, Alkaline phosphatase, 25-OH vitamin D and serum Parathormone in children with new onset nephrotic syndrome receiving vitamin D prophylaxis at a dose of 600 IU/day Vs	1. Evaluation of Bone mineral density at the time of diagnosis (first episode nephrotic syndrome) and 4 weeks after completion of Treatment (6 weeks full dose steroids and 6 weeks alternate day steroids) | 2. Evaluation of Biochemical parameters of Mineral bone disease at various time points of study. (Baseline, after 6 weeks of full dose steroids, after 6 weeks of alternate day steroids and after 4 weeks of treatment completion)

Secondary Outcome Measures

Name	Time	Method
Prevalence of Vitamin D in Children with Nephrotic syndrome before starting steroids.	At the beginning of study.

Trial Locations

Locations (1)

All India Institute of Medical Sciences; 🇮🇳 Bhopal, MADHYA PRADESH, India

All India Institute of Medical Sciences

🇮🇳Bhopal, MADHYA PRADESH, India

Dr Gujjula Ajay Kumar

Principal investigator

09182552387

gujjulaajaykumar745@gmail.com