Vitamin D to Prevent Severe Asthma Exacerbations (Vit-D-Kids Asthma)

Study Description

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Brief Summary:

This study will determine whether vitamin D3 prevents severe asthma attacks in children who have a serum vitamin D (25(OH)D) level <30 ng/ml and who are being treated with inhaled corticosteroids for asthma. Half the participants will receive vitamin D3 at a dose of 4,000 IU/day, and the other half will receive placebo.

Condition or disease	Intervention/treatment	Phase
Asthma	Drug: vitamin D3 4000 IU; Drug: Placebo	Phase 2

Detailed Description:

Results from experimental studies, observational studies, two small trials, and a recent meta-analysis suggest that vitamin D reduces the risk of severe asthma exacerbations, and that this protective effect may be due to immune modulation of viral illnesses and/or increased response to inhaled corticosteroids (ICS).

On the basis of those findings, the investigators hypothesize that vitamin D reduces the incidence of severe asthma exacerbations in high-risk school-aged children who have a serum vitamin D level <30 ng/ml and who are being treated with ICS for persistent asthma. The investigators further hypothesize that this protective effect results from reduced incidence of common viral illnesses or enhanced response to ICS. These hypotheses will be tested in a 48-week randomized double-masked placebo-controlled trial of vitamin D3 supplementation to prevent severe asthma exacerbations in 400 children aged 6 to 16 years who have vitamin D insufficiency or deficiency (a serum 25(OH)D <30 ng/ml) and experienced a severe exacerbation in the prior year (a marker of high risk for subsequent events), and who (after a run-in period) are well controlled on medium-dose inhaled corticosteroids.

Our primary aim will determine whether vitamin D3 (4,000 IU/day) reduces the risk of severe asthma exacerbations (our primary outcome) in participating children. Secondary aims will determine the efficacy of vitamin D3 supplementation in: 1) preventing severe asthma exacerbations due to viral infections, 2) reducing the daily and average cumulative dose of inhaled corticosteroids.

Study participation involves 8-9 visits, with each visit lasting between 30-90 minutes. Participation requires completion of study questionnaires, spirometry (breathing tests), and collection of blood samples (to measure vitamin D levels) and urine samples (to measure urinary calcium/creatinine ratios) at some study visits. Since the start of the study, vitamin D levels and urinary calcium/creatinine ratios have been simultaneously measured, to monitor for both vitamin D toxicity and high risk of severe vitamin D deficiency or rickets, which (should they occur) would be managed by a pediatric endocrinologist or a pediatric nephrologist, as appropriate.

All safety data for the study is regularly reviewed by a Data Safety Monitoring Board appointed by the National Heart, Lung and Blood Institute, as well as by the Institutional Review Board of each participating institution. Total study participation will last about one year.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	400 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Vitamin D to Prevent Severe Asthma Exacerbations
Actual Study Start Date :	February 22, 2016
Estimated Primary Completion Date :	July 2020
Estimated Study Completion Date :	November 2020

Arms and Interventions

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Arm	Intervention/treatment
Experimental: vitamin D3; Cholecalciferol (Vitamin D3) 4000 IU oral gel cap daily	Drug: vitamin D3 4000 IU; The vitamin D3 will be in oral gel cap form and contain 4000 International Units (IU) of cholecalciferol per gel cap.; Other Name: Cholecalciferol
Placebo Comparator: placebo; placebo formulations will be in gel cap form and identical to the active drug	Drug: Placebo; The placebo is a gel cap that is indistinguishable from the vitamin D3 gel cap.

Outcome Measures

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Primary Outcome Measures :

1. Severe asthma exacerbations [ Time Frame: 48 weeks ]

   A severe asthma exacerbation is defined as an exacerbation that meets either of these criteria: 1) Use of systemic corticosteroids (tablets, suspension, or injection), or an increase from a stable maintenance dose, for at least 3 days OR

   2) A hospitalization or ER visit because of asthma, requiring systemic corticosteroids.

Secondary Outcome Measures :

1. Severe asthma exacerbations resulting from viral infections [ Time Frame: 48 weeks ]
   A severe viral asthma exacerbation is defined as a severe asthma exacerbation (defined above) along with a positive respiratory viral panel from a nasal blow collected within 72 hours of the exacerbation.
2. Reduction in ICS dose at visit 6 [ Time Frame: 24 weeks ]

   In the absence of moderate or severe asthma exacerbations, participants may have their dose of ICS reduced by 50% if the following criteria are met at visit 6 (halfway through the Trial Phase):

   • ACT score greater than 19
   • Both pre-bronchodilator FEV1 and FEV1/FVC ≥80% of predicted
   • Use of ≤4 puffs of a rescue inhaler per week
   • ≤1 day per month with asthma symptoms preventing full participation in usual daily activities
   • Clinician's judgment regarding adequate asthma control
3. Average cumulative prescribed dose of ICS at the end of the trial [ Time Frame: 48 weeks ]

Eligibility Criteria

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Ages Eligible for Study:	6 Years to 16 Years (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• 6 to 16 years old
• Physician-diagnosed asthma for at least one year
• At least one severe asthma exacerbation in the previous year
• Use of asthma medications (daily controller medication [ICS or leukotriene inhibitor] or inhaled β2-agonist [at least three days per week]) for at least six months in the previous year
• Vitamin D insufficiency (i.e., serum vitamin D (25(OH)D level <30 ng/ml (75 nmol/L))
• FEV1 ≥70 % of predicted
• Positive bronchodilator response (i.e., increase in FEV1 ≥8% from baseline after inhaled short acting beta agonist or increased airway responsiveness to methacholine (PC20 ≤8 mg/ml if not on ICS or PC20 ≤16 mg/ml if on ICS)
• Study protocol (i.e., age-appropriate dose of Fluticasone and no other asthma controller medications) approved by the child's regular doctor
• Parental consent and child's assent to participate in the study.

Additional inclusion criteria applied after the run-in period, to be eligible for randomization:

• Adherence with ICS and study medication (≥75% use [at least 21 of 28 days]) during the run-in period
• Willingness to be randomized and complete study

Exclusion Criteria:

• Serum calcium >10.8 mg/dl
• Serum 25(OH) D <14 ng/ml (35 nmol/L)
• Chronic respiratory disorder other than asthma
• Severe asthma (intubation for asthma at any time OR ≥3 hospitalizations for asthma in previous year OR ≥6 severe asthma exacerbations in previous year)
• Hepatic/renal disease, rickets, malabsorption, or other diseases that would affect vitamin D metabolism
• Current smoking, or former smoking if ≥5 pack-years
• Immune deficiency, cleft palate or Down's syndrome
• Treatment with anticonvulsants or ≥1,000 IU/day of vitamin D2 or D3
• Chronic oral corticosteroid therapy
• Inability to perform acceptable spirometry
• Use of investigational therapies or participation in trials 30 days before or during the study
• Participant is currently breast feeding an infant
• Pregnancy
• Weight less than 10 kg
• Plans to move out of the study site area in the next year

Additional exclusion criteria applied after the run-in period:

• Any severe asthma exacerbation during the run-in period
• Need for asthma medications other than ICS and p.r.n. rescue inhalers during the run-in period

Contacts and Locations

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Contacts

Contact: Elizabeth Hartigan, RN	412-692-7060	elizabeth.hartigan@chp.edu
Contact: Cynthia Granny	412-692-7041	cynthia.granny@chp.edu

Locations

United States, California
University of California - San Francisco	Completed
San Francisco, California, United States, 94102
United States, Massachusetts
Boston Children's Hospital	Recruiting
Boston, Massachusetts, United States, 02115
Contact: Amparo Cunningham Amparito.Cunningham@childrens.harvard.edu
Principal Investigator: Wanda Phipatanakul, MD, MS
United States, Missouri
Saint Louis Children's Hospital	Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Tina Norris norris.t@wustl.edu
Principal Investigator: Leonard Bacharier, MD
United States, Ohio
Cincinnati Children's Hospital Medical Center	Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Alisha Hartmann 513-636-1882 Alisha.Hartmann@cchmc.org
Contact: Michelle England Michelle.England@cchmc.org
Principal Investigator: Theresa W. Guilbert, MD
Rainbow Babies and Children's Hospital	Recruiting
Cleveland, Ohio, United States, 44106
Contact: Laurie Logan, RN 216-844-7927 Laurie.Logan@UHhospitals.org
Principal Investigator: Kristie Ross, MD
United States, Pennsylvania
Children's Hospital of Pittsburgh of UPMC	Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Principal Investigator: Juan C Celedon, MD, DrPH

Sponsors and Collaborators

Juan Celedon, MD

Pharmavite

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Principal Investigator:	Juan C. Celedón, MD, DrPH	University of Pittsburgh
Principal Investigator:	Stephen Wisniewski, PhD	University of Pittsburgh

More Information

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Responsible Party:	Juan Celedon, MD, Niels K. Jerne Professor of Pediatrics, University of Pittsburgh
ClinicalTrials.gov Identifier:	NCT02687815 History of Changes
Other Study ID Numbers:	PRO12020541; U01HL119952 ( U.S. NIH Grant/Contract )
First Posted:	February 22, 2016
Last Update Posted:	August 1, 2018
Last Verified:	July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Keywords provided by Juan Celedon, MD, University of Pittsburgh:

Vitamin D, severe asthma exacerbations, children

Additional relevant MeSH terms:

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases	Vitamins; Vitamin D; Ergocalciferols; Cholecalciferol; Micronutrients; Growth Substances; Physiological Effects of Drugs; Bone Density Conservation Agents