Efficacy of Vitamin D Supplementation for Children With Bronchiolitis

Efficacy of Vitamin D Supplementation for Children With Bronchiolitis at Sohag University Hospital

Vitamin D plays an important role in enhancing mucosal immune defense, decreasing excessive inflammation, and increasing mucociliary clearance. Experimental studies have shown that vitamin D reduces inflammation of epithelial cells in airways infected with Respiratory Syncytial Virus and confers antiviral effects. Furthermore, several studies have shown lower serum vitamin D levels in hospitalized children with bronchiolitis. However, studies on the efficacy of Vitamin D supplementation for children with bronchiolitis are scarce with inconsistent findings. In this study, we aim to evaluate the efficacy of vitamin D supplementation in children with bronchiolitis.

Study Overview

• Status: Recruiting
• Conditions: Bronchiolitis
• Intervention / Treatment: Drug: Vitamin D3

Detailed Description

Bronchiolitis is the most frequent lower respiratory tract infection in children under two years of age, which represents a major cause of medical visits, hospital admissions, and death. This disease predominantly affects small airways with acute inflammatory edema epithelial cells, excess mucus production, and bronchospasm. The most commonly involved organisms are Respiratory Syncytial Virus (accounting for 60% of cases), followed by Rhinovirus, Parainfluenza, Metapneumovirus, Influenza, and Adenovirus. Certain factors are associated with a higher risk of severe bronchiolitis, such as prematurity, chronic lung disease, cardiac disease, immunodeficiency, neuromuscular disease, and Down syndrome.

Diagnosis of bronchiolitis relies on a constellation of clinical manifestations, including respiratory distress and wheezing preceded by viral upper respiratory tract prodrome in children under two years of age. Common manifestations of bronchiolitis are rhinorrhea, cough, wheezing, tachypnea, and increased work of breathing, including nasal flaring, retractions, and grunting. Management of bronchiolitis is mainly supportive, aiming at maintaining adequate oxygenation and hydration.

Given the high burden of bronchiolitis and the lack of specific treatment, studies have investigated several therapeutic options. One of these potential therapies is vitamin D. Vitamin D is a fat-soluble vitamin that is mainly formed in the skin after exposure to ultraviolet rays, while less than 10% is obtained from dietary sources. Besides regulation of calcium and phosphorus homeostasis, vitamin D plays an important role in enhancing mucosal immune defense, decreasing excessive inflammation, and increasing mucociliary clearance. Vitamin D deficiency is common among children, particularly in developing countries, and has been linked to an increased risk of several diseases, including bronchiolitis, pneumonia, and otitis media.

Experimental studies have shown that vitamin D reduces inflammation of epithelial cells in airways infected with Respiratory Syncytial Virus and confers antiviral effects. Furthermore, several studies have shown lower serum vitamin D levels in hospitalized children with bronchiolitis. However, studies on the efficacy of Vitamin D supplementation for children with bronchiolitis are scarce with inconsistent findings.

In this study, we aim to evaluate the efficacy of vitamin D supplementation in children with bronchiolitis.

• Study Type: Interventional
• Enrollment (Anticipated): 146
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Elsayed Abdelkreem, MD, PhD; Phone Number: +201114232126; Email: d.elsayedmohammed@med.sohag.edu.eg
• Study Contact Backup: Name: Yostena S Labeeb, MD; Phone Number: 01019492210; Email: youstinasafwat@med.sohag.edu.eg

Study Locations

• Egypt
  • Sohag, Egypt, 82524
    • Recruiting
    • Sohag University Hospital
    • Contact: Abdelrahim A Sadek, MD, PhD; Email: abdoneurology@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 2 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age between 3 to 24 months.
• Clinical diagnosis of first episode of bronchiolitis
• First 24 hours of admission.
• Stable or decreasing requirement for oxygen on 2 measurements 2 hours apart.
• Pulse rate less than 180 beat/minute.
• Respiratory rate less than 80 breath/min.
• Oxygen supplementation < 40% Fraction of inspired oxygen or < 2 L/min by nasal prong
• Not on high flow nasal cannula, continuous positive airway pressure, or mechanical ventilation at the time of enrollment.

Exclusion Criteria:

.• History of previous episodes of wheezing.

• History of apnea
• Need for positive pressure support or high flow nasal cannula at the time of enrollment.
• Chronic lung disease (requiring home oxygen, or pulmonary hypertension)
• Cardiac disease (cyanotic, hemodynamically significant [requiring diuretics], or pulmonary hypertension).
• Neuromuscular disease.
• Metabolic disease.
• Immunodeficiency.
• Chromosomal abnormalities.
• Craniofacial malformation
• Hemoglobinopathy.
• Hypercalcemia
• Chromosomal abnormalities
• Use of large doses of vitamin D (> 400 IU/day) in the last month.

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: Study group; Children receive a single dose of intramuscular 200,000 IU vitamin D3	Drug: Vitamin D3; A single dose of intramuscular 200,000 IU vitamin D3 within 24 hours of admission; Other Names: Cholecalciferol; Devarol
No Intervention: Control group; Children receiving only the standard recommended dose of vitamin D3 as 400 IU/day orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time from randomization to discharge	Time from randomization to hospital discharge (in hours)	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time from randomization to discontinuation of oxygen therapy	Time from randomization to discontinuation of oxygen therapy (in hours)	4 weeks
Time from randomization to discontinuation of intravenous fluids	Time from randomization to discontinuation of intravenous fluids (in hours)	4 weeks
Time from randomization to meeting discharge criteria	Time from randomization to meeting hospital discharge criteria (in hours)	4 weeks
Time from hospital admission to discharge	Time from hospital admission to discharge (in hours)	4 weeks
Blood level of 25-hydroxycholecalciferol	Blood level of 25-hydroxycholecalciferol	On day 3 after randomization
Serum level of ionized calcium	Serum level of ionized calcium	On day 3 after randomization
Admission to pediatric intensive care unit	Proportion of patients admitted to pediatric intensive care unit	4 weeks
Intubation	Proportion of patients who underwent endotracheal intubation	4 weeks
Mortality	Proportion of patients who died during hospital admission	4 weeks
Bronchodilator therapy	Proportion of patients who received bronchodilator therapy	4 weeks
Systemic steroids	Proportion of patients who received systemic steroids	4 weeks

Collaborators and Investigators

• Sponsor: Sohag University
• Investigators: Study Chair: Mostafa A Mohammed, MD, PhD, Sohag University

Publications and helpful links

General Publications

• Ralston SL, Lieberthal AS, Meissner HC, Alverson BK, Baley JE, Gadomski AM, Johnson DW, Light MJ, Maraqa NF, Mendonca EA, Phelan KJ, Zorc JJ, Stanko-Lopp D, Brown MA, Nathanson I, Rosenblum E, Sayles S 3rd, Hernandez-Cancio S; American Academy of Pediatrics. Clinical practice guideline: the diagnosis, management, and prevention of bronchiolitis. Pediatrics. 2014 Nov;134(5):e1474-502. doi: 10.1542/peds.2014-2742. Erratum In: Pediatrics. 2015 Oct;136(4):782.
• Wang EE, Milner RA, Navas L, Maj H. Observer agreement for respiratory signs and oximetry in infants hospitalized with lower respiratory infections. Am Rev Respir Dis. 1992 Jan;145(1):106-9. doi: 10.1164/ajrccm/145.1.106.
• Brustad N, Yousef S, Stokholm J, Bonnelykke K, Bisgaard H, Chawes BL. Safety of High-Dose Vitamin D Supplementation Among Children Aged 0 to 6 Years: A Systematic Review and Meta-analysis. JAMA Netw Open. 2022 Apr 1;5(4):e227410. doi: 10.1001/jamanetworkopen.2022.7410.
• Manti S, Staiano A, Orfeo L, Midulla F, Marseglia GL, Ghizzi C, Zampogna S, Carnielli VP, Favilli S, Ruggieri M, Perri D, Di Mauro G, Gattinara GC, D'Avino A, Becherucci P, Prete A, Zampino G, Lanari M, Biban P, Manzoni P, Esposito S, Corsello G, Baraldi E. UPDATE - 2022 Italian guidelines on the management of bronchiolitis in infants. Ital J Pediatr. 2023 Feb 10;49(1):19. doi: 10.1186/s13052-022-01392-6.
• Munns CF, Shaw N, Kiely M, Specker BL, Thacher TD, Ozono K, Michigami T, Tiosano D, Mughal MZ, Makitie O, Ramos-Abad L, Ward L, DiMeglio LA, Atapattu N, Cassinelli H, Braegger C, Pettifor JM, Seth A, Idris HW, Bhatia V, Fu J, Goldberg G, Savendahl L, Khadgawat R, Pludowski P, Maddock J, Hypponen E, Oduwole A, Frew E, Aguiar M, Tulchinsky T, Butler G, Hogler W. Global Consensus Recommendations on Prevention and Management of Nutritional Rickets. J Clin Endocrinol Metab. 2016 Feb;101(2):394-415. doi: 10.1210/jc.2015-2175. Epub 2016 Jan 8.
• Esposito S, Lelii M. Vitamin D and respiratory tract infections in childhood. BMC Infect Dis. 2015 Oct 28;15:487. doi: 10.1186/s12879-015-1196-1.
• Golan-Tripto I, Loewenthal N, Tal A, Dizitzer Y, Baumfeld Y, Goldbart A. Vitamin D deficiency in children with acute bronchiolitis: a prospective cross-sectional case- control study. BMC Pediatr. 2021 Apr 30;21(1):211. doi: 10.1186/s12887-021-02666-4.
• Khoshnevisasl P, Sadeghzadeh M, Kamali K, Ardalani A. A randomized clinical trial to assess the effect of zinc and vitamin D supplementation in addition to hypertonic saline on treatment of acute bronchiolitis. BMC Infect Dis. 2022 Jun 13;22(1):538. doi: 10.1186/s12879-022-07492-2.
• Sarhan AA, Saeed NM, Mostafa AA, Osman AM. Vitamin D supplementation for acute bronchiolitis: a double-blind randomized controlled trial. Alexandria Journal of Pediatrics. 2019;32(2):61.
• Saad K, Abd Aziz NH, El-Houfey AA, El-Asheer O, Mohamed SA, Ahmed AE, Abdel Baseer KA, Darwish MM. Trial of vitamin D supplementation in infants with bronchiolitis: a randomized, double-blind, placebo-controlled study. Pediatric Allergy, Immunology, and Pulmonology. 2015;28(2):102-6

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2023
• Primary Completion (Anticipated): April 1, 2024
• Study Completion (Anticipated): May 1, 2024

Study Registration Dates

• First Submitted: March 8, 2023
• First Submitted That Met QC Criteria: March 21, 2023
• First Posted (Actual): April 3, 2023

Study Record Updates

• Last Update Posted (Actual): April 4, 2023
• Last Update Submitted That Met QC Criteria: April 1, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Vitamin D; Children; Bronchiolitis
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Bronchitis; Bronchiolitis; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: Soh-Med-23-03-11MS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Unidentified patients' data will be available upon reasonable request after publication
• IPD Sharing Time Frame: After publication of the study
• IPD Sharing Access Criteria: Unidentified patients' data will be available upon reasonable request after publication
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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