Vitamin D3 For CGD Patients With BCGosis/Itis

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

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.

Study Overview

• Status: Completed
• Conditions: BCG; Vitamin D3; Chronic-granulomatous Disease
• Intervention / Treatment: Drug: Vitamin D3; Drug: Traditional treatment of CGD and TB

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 Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 201102
      • Children's Hospital of Fudan University
    • Shanghai, Shanghai, China
      • Children's Hospital of Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. less than 18 years' old
2. Diagnosed with CGD
3. Got BCG infection after vaccination

Exclusion Criteria:

1. Serum 25-(OH)-vit D >75 nmol/L (30 ng/mL)
2. Hyperphosphatemia
3. Hypercalcemia
4. Acute or chronic renal failure
5. Acute or chronic cardiac failure
6. Kidney stone

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Children's Hospital of Fudan University
• Investigators: Study Director: Weili Yan, Ph.D, Children's Hospital of Fudan University

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2019
• Primary Completion (Actual): December 31, 2021
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: December 5, 2018
• First Submitted That Met QC Criteria: June 12, 2019
• First Posted (Actual): June 13, 2019

Study Record Updates

• Last Update Posted (Actual): July 9, 2024
• Last Update Submitted That Met QC Criteria: July 7, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immunologic Deficiency Syndromes; Immune System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Disease Attributes; Hematologic Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Leukocyte Disorders; Phagocyte Bactericidal Dysfunction; Chronic Disease; Granuloma; Granulomatous Disease, Chronic; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: VDBCG

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No