Vitamin D3 For CGD Patients With BCGosis/Itis
Primary Purpose
Vitamin D3, Chronic-granulomatous Disease, BCG
Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Vitamin D3
Traditional treatment of CGD and TB
Sponsored by
About this trial
This is an interventional treatment trial for Vitamin D3
Eligibility 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
Sites / Locations
- Children's Hospital of Fudan UniversityRecruiting
- Children's Hospital of Fudan UniversityRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
Vitamin D Group
Control Group
Arm Description
Vitamin D3 Supplementation plus traditional treatment of CGD and TB
Traditional treatment of CGD and TB without Vitamin D Supplementation
Outcomes
Primary Outcome Measures
Mortality
Death rate among patients
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
Duration of Fever
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
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
Urine protein quantitation
Urine Calcium
Concentration of calcium in urine
Serum Levels of 25-OH Vitamin D3
Concentration of 25-OH Vitamin D3 in serum
Serum Levels of Calcium
Concentration of calcium in serum
Secondary Outcome Measures
Change in BMI
Evaluate the change in BMI by calculating weight(kg)/height(m)^2 before treatment and 1year after the treatment
Frequency of Recurrent Infections
Use frequency of recurrent infections to evaluate long-term benefits
Full Information
NCT ID
NCT03984890
First Posted
December 5, 2018
Last Updated
March 21, 2022
Sponsor
Children's Hospital of Fudan University
1. Study Identification
Unique Protocol Identification Number
NCT03984890
Brief Title
Vitamin D3 For CGD Patients With BCGosis/Itis
Official Title
Effect of Vitamin D3 Supplementation on Chronic Granulomatous Disease Patients With BCGosis/Itis
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Recruiting
Study Start Date
August 1, 2019 (Actual)
Primary Completion Date
December 31, 2021 (Actual)
Study Completion Date
December 31, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Children's Hospital of Fudan University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Vitamin D3, Chronic-granulomatous Disease, BCG
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Vitamin D Group
Arm Type
Experimental
Arm Description
Vitamin D3 Supplementation plus traditional treatment of CGD and TB
Arm Title
Control Group
Arm Type
Other
Arm Description
Traditional treatment of CGD and TB without Vitamin D Supplementation
Intervention Type
Drug
Intervention Name(s)
Vitamin D3
Intervention Description
Vitamin D3 drops 800IU/d for 3 months
Intervention Type
Drug
Intervention Name(s)
Traditional treatment of CGD and TB
Intervention Description
Anti-tuberculosis drugs, interferon-gamma
Primary Outcome Measure Information:
Title
Mortality
Description
Death rate among patients
Time Frame
8 weeks
Title
Rate of Sputum Culture acid-fast bacilli microscopy Conversion
Description
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
Time Frame
8 weeks
Title
Duration of Fever
Description
Calculate the days suffer from fevers to show the severity of the infection and the efficacy of the treatment
Time Frame
8 weeks
Title
Number of Anti-tuberculosis Drugs Used in the Treatment
Description
Calculate the number of anti-tuberculosis drugs used in the treatment to show the severity of the infection and the efficacy of the treatment
Time Frame
8 weeks
Title
Urine Protein
Description
Urine protein quantitation
Time Frame
8 weeks
Title
Urine Calcium
Description
Concentration of calcium in urine
Time Frame
8 weeks
Title
Serum Levels of 25-OH Vitamin D3
Description
Concentration of 25-OH Vitamin D3 in serum
Time Frame
8 weeks
Title
Serum Levels of Calcium
Description
Concentration of calcium in serum
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
Change in BMI
Description
Evaluate the change in BMI by calculating weight(kg)/height(m)^2 before treatment and 1year after the treatment
Time Frame
1 year
Title
Frequency of Recurrent Infections
Description
Use frequency of recurrent infections to evaluate long-term benefits
Time Frame
1 year
10. Eligibility
Sex
All
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jinqiao Sun, Ph.D.,M.D
Phone
86-21-64932909
Email
jinqiaosun@sina.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Weili Yan, Ph.D
Organizational Affiliation
Children's Hospital of Fudan University
Official's Role
Study Director
Facility Information:
Facility Name
Children's Hospital of Fudan University
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
201102
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Weili Yan, Ph.D
Email
yanwl@fudan.edu.cn
Facility Name
Children's Hospital of Fudan University
City
Shanghai
State/Province
Shanghai
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jinqiao Sun, Ph.D.,M.D
Email
jinqiaosun@sina.com
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
17513768
Citation
Martineau AR, Wilkinson KA, Newton SM, Floto RA, Norman AW, Skolimowska K, Davidson RN, Sorensen 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. doi: 10.4049/jimmunol.178.11.7190. Erratum In: J Immunol. 2007 Dec 15;179(12):8569-70.
Results Reference
background
PubMed Identifier
9784538
Citation
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. doi: 10.1128/IAI.66.11.5314-5321.1998.
Results Reference
background
PubMed Identifier
21215445
Citation
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.
Results Reference
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PubMed Identifier
16497887
Citation
Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, Ochoa MT, Schauber J, Wu K, Meinken C, Kamen DL, Wagner M, Bals R, Steinmeyer A, Zugel U, Gallo RL, Eisenberg D, Hewison M, Hollis BW, Adams JS, Bloom BR, Modlin RL. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006 Mar 24;311(5768):1770-3. doi: 10.1126/science.1123933. Epub 2006 Feb 23.
Results Reference
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PubMed Identifier
30215381
Citation
Collaborative Group for the Meta-Analysis of Individual Patient Data in MDR-TB treatment-2017; Ahmad N, Ahuja SD, Akkerman OW, Alffenaar JC, Anderson LF, Baghaei P, Bang D, Barry PM, Bastos ML, Behera D, Benedetti A, Bisson GP, Boeree MJ, Bonnet M, Brode SK, Brust JCM, Cai Y, Caumes E, Cegielski JP, Centis R, Chan PC, Chan ED, Chang KC, Charles M, Cirule A, Dalcolmo MP, D'Ambrosio L, de Vries G, Dheda K, Esmail A, Flood J, Fox GJ, Frechet-Jachym M, Fregona G, Gayoso R, Gegia M, Gler MT, Gu S, Guglielmetti L, Holtz TH, Hughes J, Isaakidis P, Jarlsberg L, Kempker RR, Keshavjee S, Khan FA, Kipiani M, Koenig SP, Koh WJ, Kritski A, Kuksa L, Kvasnovsky CL, Kwak N, Lan Z, Lange C, Laniado-Laborin R, Lee M, Leimane V, Leung CC, Leung EC, Li PZ, Lowenthal P, Maciel EL, Marks SM, Mase S, Mbuagbaw L, Migliori GB, Milanov V, Miller AC, Mitnick CD, Modongo C, Mohr E, Monedero I, Nahid P, Ndjeka N, O'Donnell MR, Padayatchi N, Palmero D, Pape JW, Podewils LJ, Reynolds I, Riekstina V, Robert J, Rodriguez M, Seaworth B, Seung KJ, Schnippel K, Shim TS, Singla R, Smith SE, Sotgiu G, Sukhbaatar G, Tabarsi P, Tiberi S, Trajman A, Trieu L, Udwadia ZF, van der Werf TS, Veziris N, Viiklepp P, Vilbrun SC, Walsh K, Westenhouse J, Yew WW, Yim JJ, Zetola NM, Zignol M, Menzies D. Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis. Lancet. 2018 Sep 8;392(10150):821-834. doi: 10.1016/S0140-6736(18)31644-1.
Results Reference
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Vitamin D3 For CGD Patients With BCGosis/Itis
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