Vitamin D3 For CGD Patients With BCGosis/Itis

Study Overview
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Brief Summary
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When children with chronic granulomatous disease (CGD) got BCG infection the treatment would be a tough task. The goal of the proposed research is to observe weather vitamin D supplementation can help the CGD children get through this challenge.

Detailed Description
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Chronic granulomatous disease (CGD) is one of primary immunodeficiency diseases. Due to the deficiency of the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase the respiratory burst of all types of phagocytic cells is badly impaired which lead to a susceptibility to infection among CGD patients. BCG vaccine is wildly used in China to avoid severe tuberculosis infection. Children are supposed to get BCG vaccine injected within 24 hours after birth. When patients with CGD got the vaccination of BCG they will easily got infected. And due to the immunodeficiency of these children, the infection cannot be cure by normal treatment. Vitamin D supplementation was used to treat tuberculosis in the pre-antibiotic era and is reported to have influence on immune system especially on monocytes and macrophages thus may help CGD children defend the BCG infection. In addition, studies show that 1,25-Dihydroxyvitamin D3 can induce nitric oxide synthase thus may up regulate NO production and help host defense against human tuberculosis without the help of NADPH oxidase. Other researches indicate that Vitamin D and the expression of vitamin D receptor may lead to induction of antimicrobial peptide such as LL-37 which help macrophages kill the intracellular Mycobacterium tuberculosis. These discoveries indicated that vitamin D may induce immune response against BCG in a nontraditional way. Therefore, when CGD patients face BCG infection, add vitamin D supplementation to the treatment may help them survive this challenge. Since there have had clinical trials revealing that intermittent high dose vitamin D3 supplementation as 2.5mg per 14 days only receive positive effect on partial patients the investigators decide to choose a mild dose treatment as 800IU/d for 3 month to see if things get different in this way.

Official Title
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Effect of Vitamin D3 Supplementation on Chronic Granulomatous Disease Patients With BCGosis/Itis

Conditions
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Vitamin D3, Chronic-granulomatous Disease, BCG

Intervention / Treatment
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* Drug: Vitamin D3
* Drug: Traditional treatment of CGD and TB


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: less than 18 years' old Diagnosed with CGD Got BCG infection after vaccination Exclusion Criteria: Serum 25-(OH)-vit D >75 nmol/L (30 ng/mL) Hyperphosphatemia Hypercalcemia Acute or chronic renal failure Acute or chronic cardiac failure Kidney stone

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin D Group<br>Vitamin D3 Supplementation plus traditional treatment of CGD and TB | Drug: Vitamin D3<br>* Vitamin D3 drops 800IU/d for 3 months<br>Drug: Traditional treatment of CGD and TB<br>* Anti-tuberculosis drugs, interferon-gamma<br>|
| Other: Control Group<br>Traditional treatment of CGD and TB without Vitamin D Supplementation | Drug: Traditional treatment of CGD and TB<br>* Anti-tuberculosis drugs, interferon-gamma<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | Death rate among patients | 8 weeks | 
| Rate of Sputum Culture acid-fast bacilli microscopy Conversion | If sputum culture and acid-fast bacilli microscopy show positive results before treatments, compare the results before and after treatments to see if the rate that results changed from positive to negative differ between control group and vitamin D group | 8 weeks | 
| Duration of Fever | Calculate the days suffer from fevers to show the severity of the infection and the efficacy of the treatment | 8 weeks | 
| Number of Anti-tuberculosis Drugs Used in the Treatment | Calculate the number of anti-tuberculosis drugs used in the treatment to show the severity of the infection and the efficacy of the treatment | 8 weeks | 
| Urine Protein | Urine protein quantitation | 8 weeks | 
| Urine Calcium | Concentration of calcium in urine | 8 weeks | 
| Serum Levels of 25-OH Vitamin D3 | Concentration of 25-OH Vitamin D3 in serum | 8 weeks | 
| Serum Levels of Calcium | Concentration of calcium in serum | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in BMI | Evaluate the change in BMI by calculating weight(kg)/height(m)^2 before treatment and 1year after the treatment | 1 year | 
| Frequency of Recurrent Infections | Use frequency of recurrent infections to evaluate long-term benefits | 1 year |