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

NCT ID: NCT02687815

Last Updated: 2021-08-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 192 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-22
• Study Completion Date: 2019-09-17

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.

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.

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

vitamin D3

Cholecalciferol (Vitamin D3) 4000 IU oral gel cap daily

Group Type: EXPERIMENTAL

vitamin D3 4000 IU

Intervention Type: DRUG

The vitamin D3 will be in oral gel cap form and contain 4000 International Units (IU) of cholecalciferol per gel cap.

placebo

placebo formulations will be in gel cap form and identical to the active drug

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

The placebo is a gel cap that is indistinguishable from the vitamin D3 gel cap.

Interventions

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.

Intervention Type: DRUG

Placebo

The placebo is a gel cap that is indistinguishable from the vitamin D3 gel cap.

Intervention Type: DRUG

Other Intervention Names

Cholecalciferol

Eligibility 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.

• 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

• 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

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pharmavite LLC

INDUSTRY

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Juan Celedon, MD

OTHER

Sponsor Role: lead

Responsible Party

Juan Celedon, MD

Niels K. Jerne Professor of Pediatrics

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Juan C. Celedón, MD, DrPH

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Stephen Wisniewski, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

University of California - San Francisco

San Francisco, California, United States

National Jewish Health

Denver, Colorado, United States

Boston Children's Hospital

Boston, Massachusetts, United States

Saint Louis Children's Hospital

St Louis, Missouri, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Rainbow Babies and Children's Hospital

Cleveland, Ohio, United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Countries

United States

References

Han YY, Forno E, Bacharier LB, Phipatanakul W, Guilbert TW, Cabana MD, Ross K, Blatter J, Rosser FJ, Durrani S, Luther J, Wisniewski SR, Celedon JC. Vitamin D supplementation, lung function and asthma control in children with asthma and low vitamin D levels. Eur Respir J. 2021 Oct 28;58(4):2100989. doi: 10.1183/13993003.00989-2021. Print 2021 Oct.

Reference Type: DERIVED

PMID: 34326185 (View on PubMed)

Forno E, Bacharier LB, Phipatanakul W, Guilbert TW, Cabana MD, Ross K, Covar R, Gern JE, Rosser FJ, Blatter J, Durrani S, Han YY, Wisniewski SR, Celedon JC. Effect of Vitamin D3 Supplementation on Severe Asthma Exacerbations in Children With Asthma and Low Vitamin D Levels: The VDKA Randomized Clinical Trial. JAMA. 2020 Aug 25;324(8):752-760. doi: 10.1001/jama.2020.12384.

Reference Type: DERIVED

PMID: 32840597 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

U01HL119952

Identifier Type: NIH

Identifier Source: secondary_id

View Link

PRO12020541

Identifier Type: -

Identifier Source: org_study_id