AsthmaPhase 2NCT02687815

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

A Phase 2 study testing vitamin D3 4000 IU in people with Asthma, run by Juan Celedon, MD at 7 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Trial 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. Read more about this study

Who is it for?: Ages 6 to 16 years
Conditions the study is for: Asthma
What is being tested?: vitamin D3 4000 IU
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 192 participants
Where: 7 sitesUnited States
Study dates: 22 Feb 2016to 17 Sep 2019
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 6 to 16 years
All sexes
No healthy volunteers
Child

Who may be able to join

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

Show all 12Show fewer

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

Who cannot join

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

Show all 18Show fewer

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

Trial locations and contacts

7 sites in 1 country.

City, postcode or hospital

7 sites in 1 country

United States7 sites

Boston Children's Hospital
Boston, Massachusetts, 02115
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Rainbow Babies and Children's Hospital
Cleveland, Ohio, 44106
National Jewish Health
Denver, Colorado, 80206
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
University of California - San Francisco
San Francisco, California, 94102
Saint Louis Children's Hospital
St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: Vitamin D to Prevent Severe Asthma Exacerbations

Read the 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
Being tested: vitamin D3 4000 IU, Placebo
Keywords: Vitamin D, severe asthma exacerbations, children
Medical subject headings: Asthma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

vitamin D3 4000 IUDrug
Also called Cholecalciferol
The vitamin D3 will be in oral gel cap form and contain 4000 International Units (IU) of cholecalciferol per gel cap.
PlaceboDrug
The placebo is a gel cap that is indistinguishable from the vitamin D3 gel cap.

Study groups in NCT02687815
Study group	Role	What they receive
vitamin D3	Experimental	Cholecalciferol (Vitamin D3) 4000 IU oral gel cap daily Receives: Drug: vitamin D3 4000 IU
placebo	Placebo comparator	placebo formulations will be in gel cap form and identical to the active drug Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Days to a Severe Asthma Exacerbation
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.
Measured: 48 weeks

Secondary outcomes (3)

Days to Viral-induced Severe Exacerbation
A severe viral asthma exacerbation is defined as a severe asthma exacerbation [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] along with a positive respiratory viral panel from a nasal blow collected within 72 hours of the exacerbation.
Measured: 48 weeks
Proportion of Participants in Whom Fluticasone Dose Was Halved at Visit 6
In the absence of moderate or severe asthma exacerbations, participants may have their dose of inhaled corticosteroids (ICS) reduced by 50% if the following criteria are met at visit 6 (halfway through the Trial Phase):
- Asthma Control Test (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
Measured: 24 weeks
Average Cumulative Prescribed Dose of ICS at the End of the Trial
The average cumulative dose of inhaled corticosteroids (ICS) during the study period
Measured: 48 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

22 Feb 201617 Sep 2019

First posted22 Feb 2016 (estimated)
Study start22 Feb 2016
Primary completion17 Sep 2019
Study completion17 Sep 2019

Why it stopped: Futility of vitamin D supplementation based on protocol threshold: \<30% conditional power to detect pre-specified effect- 16% reduction in severe exacerbations.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for AsthmaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 192 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02687815
Sponsor's protocol ID: PRO12020541
Other IDs: U01HL119952
Status last verified: Aug 2021
First submitted: 11 Feb 2016
Last updated: 12 Aug 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No

Publications

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.
PubMed 34326185
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.
PubMed 32840597

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Asthma trials

Study at a glance

From the registry record, last updated by the sponsor on 12 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Vitamin D to Prevent Severe Asthma Exacerbations
ClinicalTrials.gov ID: NCT02687815
Acronym / sponsor ID: PRO12020541
Conditions: Asthma
Keywords: Vitamin D, severe asthma exacerbations, children
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Futility of vitamin D supplementation based on protocol threshold: \<30% conditional power to detect pre-specified effect- 16% reduction in severe exacerbations.
Enrolment: 192 participants (actual)
Lead sponsor: Juan Celedon, MDUniversity, hospital or other
Collaborators: Pharmavite LLC, National Heart, Lung, and Blood Institute (NHLBI)
Study start: 22 Feb 2016 (actual)
Primary completion: 17 Sep 2019 (actual)
Study completion: 17 Sep 2019 (actual)
First posted: 22 Feb 2016 (estimated)
Results: Posted 3 Nov 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
vitamin D3	Experimental	Drug: vitamin D3 4000 IUCholecalciferol (Vitamin D3) 4000 IU oral gel cap daily
placebo	Placebo comparator	Drug: Placeboplacebo formulations will be in gel cap form and identical to the active drug

Who may qualify

Ages: 6 to 16 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (12 listed)

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))

Key exclusion criteria (18 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
vitamin D3 4000 IUAlso: CholecalciferolThe vitamin D3 will be in oral gel cap form and contain 4000 International Units (IU) of cholecalciferol per gel cap.	Drug	vitamin D3
PlaceboThe placebo is a gel cap that is indistinguishable from the vitamin D3 gel cap.	Drug	placebo

Primary outcome

Days to a Severe Asthma Exacerbation
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.

3 secondary outcomes

Days to Viral-induced Severe Exacerbation
Time frame: 48 weeks
Proportion of Participants in Whom Fluticasone Dose Was Halved at Visit 6
Time frame: 24 weeks
Average Cumulative Prescribed Dose of ICS at the End of the Trial
Time frame: 48 weeks

Results and safety

Results posted to the registry on 3 Nov 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Vitamin D3	96	92
Placebo	96	88

Primary outcome: Days to a Severe Asthma Exacerbation

Time frame: 48 weeks. Mean (Standard Deviation). Unit: Days

Measure	Vitamin D3 n = 96	Placebo n = 96
Value	240 (105.8)	253 (101.3)

Vitamin D3 vs Placebo: Hazard Ratio (HR): 1.13 (95% CI 0.69 to 1.85), p = 0.63, Regression, Cox

Population analysed: Intent to treat population across the 48-week study period

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: 48 weeks. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Vitamin D3	9 of 96 (9.4%)	5 of 96 (5.2%)	0 of 96
Placebo	7 of 96 (7.3%)	4 of 96 (4.2%)	0 of 96

Limitations and caveats (from the sponsor): Limited statistical power to determine if vitamin D supplementation prolongs the time to a severe asthma exacerbation in children with vitamin D level \<20 ng/ml.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 34326185Han 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.
Derived from this study: PubMed 32840597Forno 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Juan C. Celedón, MD, DrPH principal investigator

University of Pittsburgh

Stephen Wisniewski, PhD principal investigator

University of Pittsburgh

7 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing vitamin D3 4000 IU in people with Asthma, run by Juan Celedon, MD at 7 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 12 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Nov 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Days to a Severe Asthma Exacerbation (time frame: 48 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02687815, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2021.