| CTRI Number |
CTRI/2025/03/082823 [Registered on: 19/03/2025] Trial Registered Prospectively |
| Last Modified On: |
19/03/2025 |
| Post Graduate Thesis |
Yes |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group Trial |
|
Public Title of Study
|
Comparing effect of two different prophylactic Vitamin D dosage on Bone Health in a child with Nephrotic Syndrome (1st Episode) |
|
Scientific Title of Study
|
To compare the effect of two prophylactic Vitamin D regimen on Bone mineral health in Children with first episode Nephrotic syndrome - Open labelled Randomized controlled trial |
| Trial Acronym |
NIL |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Gujjula Ajay Kumar |
| Designation |
Post graduate trainee |
| Affiliation |
AIIMS Bhopal |
| Address |
Pediatric ward,
Department of Pediatrics,
AIIMS Bhopal, Saket Nagar,
Habibganj road, Bhopal,
Madhya pradesh.
Bhopal
MADHYA PRADESH
462020
India |
| Phone |
09182552387 |
| Fax |
|
| Email |
gujjulaajaykumar745@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Mahesh Maheshwari |
| Designation |
Professor |
| Affiliation |
AIIMS Bhopal |
| Address |
Department of Pediatircs,
Aiims bhopal, saket nagar, Habibganj
Bhopal
MADHYA PRADESH
462020
India |
| Phone |
9425428596 |
| Fax |
|
| Email |
mahesh.pediatrics@aiimsbhopal.edu.in |
|
Details of Contact Person
Public Query
|
| Name |
Girish Chandra Bhatt |
| Designation |
Professor |
| Affiliation |
AIIMS Bhopal |
| Address |
Department of Pediatircs,
Aiims bhopal, saket nagar, Habibganj
Bhopal
MADHYA PRADESH
462020
India |
| Phone |
8462002229 |
| Fax |
|
| Email |
drgcbhatt@gmail.com |
|
|
Source of Monetary or Material Support
|
| AIIMS Bhopal, Saket Nagar, Habibganj road, Bhopal, Madhya pradesh, India - 462020. |
|
|
Primary Sponsor
|
| Name |
AIIMS Bhopal |
| Address |
AIIMS bhopal, saket nagar, Habibganj,
Bhopal 462020 |
| Type of Sponsor |
Government medical college |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Gujjula Ajay Kumar |
All India Institute of Medical Sciences |
Pediatric ward,
Department of pediatrics,
AIIMS bhopal, saket nagar, Habibganj road,
Bhopal, Madhya pradesh-462020.
Bhopal
MADHYA PRADESH |
09182552387
gujjulaajaykumar745@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institutional Human Ethics committee - student research (IHEC - SR) |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: N049||Nephrotic syndrome with unspecified morphologic changes, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Vitamin D 1000IU and Calcium 750mg |
In Group B, Vitamin D dose will be 1000 IU along with calcium 750 mg for 12 weeks (as first episode treatment is for 12 weeks) - Maximum prophylactic dose that can be given will be 1000IU of vitamin D in high risk groups |
| Intervention |
Vitamin D 600IU and Calcium 750mg |
In Group A, Vitamin D dose will be 600 IU along with calcium 750 mg for 12 weeks (as first episode treatment is for 12 weeks)- To find out least possible dose of vitamin D for prevention of steroid induced bone loss. |
|
|
Inclusion Criteria
|
| Age From |
1.00 Year(s) |
| Age To |
12.00 Year(s) |
| Gender |
Both |
| Details |
All Children between the ages of 1-12 years diagnosed as first episode Nephrotic syndrome. |
|
| ExclusionCriteria |
| Details |
1. Children with clinical or biochemical evidence of Metabolic bone disease including
vitamin D deficiency.
2. Children with pre-existing Chronic Liver Disease or Autoimmune Disorder.
3. Children with history of prolong steroids intake.
4. Children who develop resistance to steroids during the course of treatment. |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Sequentially numbered, sealed, opaque envelopes |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
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
D prophylaxis at a dose of 600 IU/day Vs 1000IU/day.
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
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) |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| Prevalence of Vitamin D in Children with Nephrotic syndrome before starting steroids. |
At the beginning of study. |
|
|
Target Sample Size
|
Total Sample Size="56"
Sample Size from India="56"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 2/ Phase 3 |
|
Date of First Enrollment (India)
|
30/03/2025 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="6"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
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 of
idiopathic Nephrotic syndrome is 1·15-16·9 per 100 000 children, varying
by ethnicity and region. Therapy for the initial
episode 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 40
mg) on alternate days for the next 6 weeks, and then discontinued. There
is a significant risk that children with nephrotic syndrome may experience side
effects from the high doses of steroids we are administering. Osteoporosis is the most common serious adverse effect of steroid therapy
encountered in 30-50% of patients. Mechanism of Corticosteroids induced osteoporosis – Corticosteroids increase the expression of RANK-L
and CSF-1 and decrease osteo-protegrin expression by human osteoblastic and stromal cells, which in turn results in
increased osteo-clastogenesis and bone resorption. Corticosteroids promote mature osteoblasts programmed cell death, or apoptosis. Glucocorticoids inhibit the synthesis of type I
collagen, the major component of bone extracellular matrix, with a consequent
decrease in bone matrix available for mineralization. The bone loss predominantly occurs in trabecular bones. Therefore, more
severe osteopenia is seen in vertebrae and ribs. Evaluation of Bone metabolic health using Biochemical Parameters –
Calcium, Phosphate, ALP, Vitamin D and Parathormone. Gold standard
investigation for assessing Bone metabolic health (BMD) – DEXA (Dual Energy
X-ray Absorptiometry),
which is advised yearly for patients receiving long-term steroids. In addition, they should also receive
prophylactic calcium and vitamin D supplements. Vitamin
D deficiency has been identified in many types and stages of nephrotic
syndromes, which is exacerbated by continuous biochemical abnormalities
resulting in a loss of vitamin D binding globulin and proteinuria. The supplementation of
vitamin D is indicated primarily for restoration of the bone health in these
patients, which is documented in various studies as improvement in biochemical
and radiological parameters of bone health and is recommended by
international and national guidelines. Reason for
supplementation of Vitamin D and calcium together - Calcium is actively absorbed from the small
intestine in the presence of Vitamin D. Hydroxyapatite crystals are formed by phosphorus and calcium
and serve to mineralize and fortify bones. Therefore, for optimal bone
mineralization, calcium and vitamin D supplements are required. Prophylactic
doses given in Children at high-risk category is between 400IU – 1000IU per day
along with calcium as per IAP Guidelines. Justification
for the conduct of the study- As there is no universal recommendation for
prophylactic supplementation of Vitamin D and calcium in first episode of NS,
who is on steroids for < 3 months. But recent studies showed that there is
significant bone loss even in children on steroids for < 3 months. This
facilitates need for prophylactic Vitamin D and calcium supplementation in
children with first episode nephrotic syndrome. Recent guidelines by Indian
academy of Pediatrics suggested to supplement Vitamin D and calcium in children
with Nephrotic syndrome (Grade 3 evidence) but dose is not suggested. Very few
studies are available in literature on need and dose of vitamin D in nephrotic
syndrome especially in first episode. As per guidelines Vitamin D and Calcium
prophylactic dose ranges from 400IU – 1000 IU & 600 – 800 mg per day
respectively 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 D
showed a significant change in BMD and Biochemical parameters, but it is not
adequate dose to prevent Bone loss. This study is being done to find out
efficacy of 600IU vs. 1000IU dosing
regimens in preventing steroid induced bone loss in children with first episode
Nephrotic syndrome. |