Vitamin D3 For CGD Patients With BCGosis/Itis
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Vitamin D Group Vitamin D3 Supplementation plus traditional treatment of CGD and TB |
Drug: Vitamin D3
Vitamin D3 drops 800IU/d for 3 months
Drug: Traditional treatment of CGD and TB
Anti-tuberculosis drugs, interferon-gamma
|
| Other: Control Group Traditional treatment of CGD and TB without Vitamin D Supplementation |
Drug: Traditional treatment of CGD and TB
Anti-tuberculosis drugs, interferon-gamma
|
Outcome Measures
Primary Outcome Measures
- Mortality [8 weeks]
Death rate among patients
- Rate of Sputum Culture acid-fast bacilli microscopy Conversion [8 weeks]
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
- Duration of Fever [8 weeks]
Calculate the days suffer from fevers to show the severity of the infection and the efficacy of the treatment
- Number of Anti-tuberculosis Drugs Used in the Treatment [8 weeks]
Calculate the number of anti-tuberculosis drugs used in the treatment to show the severity of the infection and the efficacy of the treatment
- Urine Protein [8 weeks]
Urine protein quantitation
- Urine Calcium [8 weeks]
Concentration of calcium in urine
- Serum Levels of 25-OH Vitamin D3 [8 weeks]
Concentration of 25-OH Vitamin D3 in serum
- Serum Levels of Calcium [8 weeks]
Concentration of calcium in serum
Secondary Outcome Measures
- Change in BMI [1 year]
Evaluate the change in BMI by calculating weight(kg)/height(m)^2 before treatment and 1year after the treatment
- Frequency of Recurrent Infections [1 year]
Use frequency of recurrent infections to evaluate long-term benefits
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Children's Hospital of Fudan University | Shanghai | Shanghai | China | 201102 |
| 2 | Children's Hospital of Fudan University | Shanghai | Shanghai | China |
Sponsors and Collaborators
- Children's Hospital of Fudan University
Investigators
- Study Director: Weili Yan, Ph.D, Children's Hospital of Fudan University
Study Documents (Full-Text)
None provided.More Information
Publications
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- Martineau AR, Timms PM, Bothamley GH, Hanifa Y, Islam K, Claxton AP, Packe GE, Moore-Gillon JC, Darmalingam M, Davidson RN, Milburn HJ, Baker LV, Barker RD, Woodward NJ, Venton TR, Barnes KE, Mullett CJ, Coussens AK, Rutterford CM, Mein CA, Davies GR, Wilkinson RJ, Nikolayevskyy V, Drobniewski FA, Eldridge SM, Griffiths CJ. High-dose vitamin D(3) during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial. Lancet. 2011 Jan 15;377(9761):242-50. doi: 10.1016/S0140-6736(10)61889-2. Epub 2011 Jan 5.
- Martineau AR, Wilkinson KA, Newton SM, Floto RA, Norman AW, Skolimowska K, Davidson RN, Sørensen OE, Kampmann B, Griffiths CJ, Wilkinson RJ. IFN-gamma- and TNF-independent vitamin D-inducible human suppression of mycobacteria: the role of cathelicidin LL-37. J Immunol. 2007 Jun 1;178(11):7190-8. Erratum in: J Immunol. 2007 Dec 15;179(12):8569-70.
- Rockett KA, Brookes R, Udalova I, Vidal V, Hill AV, Kwiatkowski D. 1,25-Dihydroxyvitamin D3 induces nitric oxide synthase and suppresses growth of Mycobacterium tuberculosis in a human macrophage-like cell line. Infect Immun. 1998 Nov;66(11):5314-21.
- VDBCG