Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT06073925 |
| Other study ID # |
MS.23.03.2332 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
Early Phase 1
|
| First received |
|
| Last updated |
|
| Start date |
December 2023 |
| Est. completion date |
October 2024 |
Study information
| Verified date |
October 2023 |
| Source |
Mansoura University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Immune thrombocytopenia is an autoimmune disease in which platelets are targeted by the host
immune system. Platelet depletion occurs when autoantibodies targeting glycoproteins (αIIb-β3
and GPIb) found on the surface of platelets opsonize the cells, resulting in destruction by
macrophages. These antibodies can also bind to megakaryocytes and prevent complete
maturation, which results in lowered levels of platelet production Vitamin D (VD) or
1,25-dihydroxyvitamin D, may be a potent immunomodulator, and it may have potential
therapeutic use in many autoimmune diseases In 1991, researchers found that the production of
interleukin (IL)-6 and IL-2 in cell cultures were reduced by 1,25(OH)2D3 VD deficiency is
very common in children with either newly diagnosed or chronic ITP form.Correlation between
hypovitaminosis D and a higher incidence of infections and autoimmune diseases was reported
as well Case-Control interventional study (over time each participant will be randomized to
be enrolled in one of either study arms in a random sequence). To evaluate the efficacy of VD
supplementation as an adjuvant therapy in chronic ITP children and its effect on platelet
count and bleeding score.
The participants will be - Children from 1 year to 18 years diagnosed with Chronic ITP with
platelet count <100,000/microL.
Patients groups will be:
Patients of Chronic ITP aged from 1year till 18 years old . in this study will be divided
into 2 groups ● Group A : All patients with VIT D insufficiency(The preferred level for
25(OH)D is now recommended by many experts to be >30 ng/ml) will receive supplementary
Vitamin D3(NIVAGEN Vitamin D3 Cholecalciferol 50000 IU) oral once weekly for 3 months as
adjuvant therapy in combination with their treatment for ITP.
● Group B : patients in this group have sufficient VIT D level and will be divided into 2
groups :
- Group 1 B :will receive their standard treatment for ITP with VIT D.
- Group 2 B :will receive their standard treatment for ITP without VIT D. Complete blood
picture will be made at the beginning of study then monthly to evaluate the number of
platelets that expected to increase after VD supplementation
Description:
Introduction
Immune thrombocytopenia is an autoimmune disease in which platelets are targeted by the host
immune system. Platelet depletion occurs when autoantibodies targeting glycoproteins (αIIb-β3
and GPIb) found on the surface of platelets opsonize the cells, resulting in destruction by
macrophages. These antibodies can also bind to megakaryocytes and prevent complete
maturation, which results in lowered levels of platelet production.
ITP of childhood is characterized by isolated thrombocytopenia (platelet count
<100,000/microL with normal white blood cell count, hemoglobin, and blood smear).
The incidence of ITP in children is approximately 4-8 per 100,000 person-year . A recent
history of viral illness is described in 50-65% of children with ITP. The peak age is 1-4 yr.
ITP seems to occur more often in late winter and spring after the peak season of viral
respiratory illness.
ITP can be classified by disease duration into; newly diagnosed (0-3 months), persistent
(>3-12 months), or chronic (>12 months). The term "refractory" has been used to refer to
patients who failed to improved after splenectomy.
Current treatment involves intravenous corticosteroids show efficacy in 50% to 80% of cases,
but if treatment is stopped, the remission rate is only 10% to 30% immunosuppressants such as
mycophenolate mofetil and azathioprine, cyclophosphamide, and intravenous immunoglobulin
(IVIg).
Anti-D immunoglobulin that can only be given to RhD-positive individuals, thus limiting
treatment options for RhD-negative persons. Rituximab has also been tried, and combinations
of therapies have been used with some success .
If patients are refractory to drug treatments, splenectomy is a second line option;
two-thirds of patients who undergo splenectomy for ITP respond to the treatment . However,
complications may arise from this surgical procedure including hemorrhage, abscess, sepsis,
thrombosis and death and relapse of ITP occurs in a median of 15% of patients .
Vitamin D (VD) or 1,25-dihydroxyvitamin D, may be a potent immunomodulator, and it may have
potential therapeutic use in many autoimmune diseases . In 1991, researchers found that the
production of interleukin (IL)-6 and IL-2 in cell cultures were reduced by 1,25(OH)2D3.
It was postulated that 1,25(OH) 2D3 may inhibit the production and function of IL-6 and,
therefore, regulate lymphocyte functions. Activation of the vitamin D receptors (VDRs) is
known to alter immune cell transcriptional patterns, proliferation and differentiation
through several intracellular pathways . Both CD4+ and CD8+ lymphocytes contain significant
amounts of VDRs, and thus it is reasonable to conclude that 1,25(OH)2D3 may play a role in
the regulation of the immune response .
VD deficiency is very common in children with either newly diagnosed or chronic ITP
form.Correlation between hypovitaminosis D and a higher incidence of infections and
autoimmune diseases was reported as well.
There is an inverse association between TNF-α and VD levels in a healthy population and there
is a protective association found for VD against inflammatory diseases such as inflamatory
heart disease and rheumatoid arthritis. However, more studies are needed to precisely
characterize the relationship between VD and TNF-α. Vitamin D therapy may show promise as
adjunct to anti-TNF-α in autoimmune disease such as ITP .
Aim of the work:
To evaluate the efficacy of VD supplementation as an adjuvant therapy in chronic ITP children
and its effect on platelet count and bleeding score.
Research gap:
To the best of our knowledge, no previous studies evaluating the effect of VD supplementation
on chronic ITP children (only case reports).
Patients and methods
A randomized controlled trial will be conducted in the period from 2023 to 2024.
1. -Study design:
Case-Control interventional study (over time each participant will be randomized to be
enrolled in one of either study arms in a random sequence).
2. - Participants:
A - Inclusion criteria:
- Chirdren from 1 year to 18 years.
- Diagnosed with Chronic ITP .
- Platelet count <100,000/microL.
B- Exclusion criteria:
● Other causes of thrombocytopenia.
● Acute and persistant ITP.
● Dysmorphic feature.
● Patients with other comorbidities.
3. -Study location:
Mansoura University Children Hospital- Hematology Out Patient Clinc. 4- Study duration:
Over one year from 2023 to 2024
5- Study methodology:
A- Randomization:
1. Procedure: Simple .
2. Allocation concealment: using sequentially numbered sealed envelop. 3- Sample size:
pilot study.
B- Patients groups:
Patients of Chronic ITP aged from 1year till 18 years old . in this study will be divided
into 2 groups ● Group A : All patients with VIT D insuffeciency(The preferred level for
25(OH)D is now recommended by many experts to be >30 ng/ml) will receive supplementary
Vitamin D3(NIVAGEN Vitamin D3 Cholecalciferol 50000 IU) oral once weekly for 3 months as
adjuvant therapy in combination with their treatment for ITP.
● Group B : patients in this group have suffecient VIT D level and will be divided into 2
groups :
- Group 1 B :will receive their standard treatment for ITP with VIT D.
- Group 2 B :will receive their standard treatment for ITP without VIT D.
Each patient in group A and group 1b will be provided with patient dairy to document
patient's compliance:
1. Patients considered fulfilling >75% of the weekly oral VD their compliance will be
considered (good compliance)
2. Patients fulfilling 50%-75% will be considered (fair compliance).
3. Patients fulfilling <50% will be considered (poor compliance).
C- History and examination:
1. Age.
2. Sex.
3. Duration of the illness.
4. Bleeding score, Each patient will be undergone examination for bleeding manifestation,
bleeding score will be done for all patients and assessment of patients for growth
parameters according to Table (1) Table (1): Scale of Bolton-Maggs and Moon -for
severity of bleeding.
None/mild ▪ No bleeding at all or bruising, petechiae, occasaional mild epistaxis with
very little or no interference with daily living.
Moderate ▪ More severe skin manifestation with some mucosal bleeding and more
troublesome epistaxis or menorrhagia.
Sever ▪ Bleeding episodes (epistaxis, melena, menorrhagia, and - or intracranial
hemorrhage ) requiring hospital admission and - or blood transfusion, that is symptoms
interfering seriously with quality of life.
5. Current treatment.
6. Examination for any bleeding signs.
D- laboratory assessment:
- Complete blood picture at the begining of study then monthly.
- Estimation of Vitamin D level by ELISA .
Ethical consideration:
Privacy was maintained by identification of the patients by coded numbers and all private
data of the patients such as name, address and phone numbers didn't appear in the research
instead, a code number was assigned to identify research participant.
The study protocol will be subjected for approval from Institutional Review Board of faculty
of medicine - Mansoura University .
The merits of the study were explained to the participant.
The subjects that were involved in the research had the right to withdraw from the study at
any time.
An informed consent obtained from all parents before enrollment of their children in the
study.
Statistical Analysis :
All data will be collected, processed &analyzed using SPSS version 20. Quantitative data will
be expressed as mean ±SD for parametric & median (minimum - maximum) for non-parametric,
after testing norm- ality using Kolmogrov- Smirnov test. Categorical variables will be
described as number & percentage. The proper statistical test will be applied according to
data. All tests will be 2 tailed & P value will be considered significant < 0.05.
