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WheezingPhase 4D-WheezeNCT01601847

Wheezing in Black Preterm Infants: Impact of Vitamin D Supplementation Strategy

A Phase 4 study testing Cholecalciferol in people with Wheezing and Allergy, run by Case Western Reserve University at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The goal of this study is to identify a vitamin D supplementation strategy that best promotes the lung, immune, and overall health of black infants born preterm (28-36 weeks gestational age). Read more about this study

Who is it for?
Ages Up to 1 year
Conditions the study is for
Wheezing, Allergy
What is being tested?
Cholecalciferol
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
300 participants
Where
5 sitesUnited States
Study dates
Jan 2013to 12 Mar 2017
Phase
Phase 4
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 Up to 1 year
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 28 0/7-36 6/7 weeks gestational age (GA) at birth;
  • family identifies the child as black or African American;
  • < 28 days of supplemental oxygen (subsequent oxygen therapy for < 72 hrs for a brief subsequent illness or surgery will be allowed);
  • admitted to a participating site NICU, special care nursery, transitional care nursery, or well-baby nursery as a neonate; and
  • < 40 weeks corrected GA at enrollment.

Who cannot join

  • BPD (> 28 days of supplemental oxygen);
  • pre-existing diagnosis of moderate to severe osteopenia of prematurity and/or alkaline phosphatase > 700;
  • history of fracture;
  • gastrointestinal surgery, including for NEC;
  • known gastrointestinal malabsorption;
  • major congenital anomaly;
Show all 12Show fewer
  • congenital pulmonary or airway disorder (e.g., cystic fibrosis, tracheomalacia, swallowing disorder, bronchopulmonary sequestration);
  • documented wheezing or stridor prior to enrollment;
  • previous vit. D supplementation with > 400 IU/day;
  • family plans to move more than 60 miles from CWRU or other pre-defined radius at other sites;
  • baseline hypo- or hypercalcemia, hypo- or hyperphosphatemia; and
  • baseline 25(OH) D level < 10 ng/ml.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Case Western Reserve University

    Cleveland, Ohio, 44023

  • University Hospitals

    Cleveland, Ohio, 44023

  • MetroHealth Medical Center

    Cleveland, Ohio, 44109

  • Montefiore Medical Center

    New York, New York, 10467

Other trials in United States

About this study

The goal of this study is to identify a vitamin D supplementation strategy that best promotes the lung, immune, and overall health of black infants born preterm (28-36 weeks gestational age). This is a high risk population that seems to have unique vitamin D needs, and inappropriate supplementation may promote wheezing or allergy. The results of this study will help form nutritional recommendations for the approximately 100,000 black infants born at 30-36 weeks gestational age in the U.S. every year.

Read the detailed description

Black infants face the highest rates of prematurity in the U.S. (18%), have high rates of prematurity-associated wheezing illnesses, and tend to have lower vitamin D levels. The goal of this [comparative effectiveness] study is to identify a vit. D supplementation strategy that minimizes recurrent wheezing in infancy. Long recognized as important for bone health, a growing body of evidence suggests that vit. D may play a role in the regulation and development of many organ systems. The D pathway regulates lung inflammation and impacts morphogenesis, structure, and cell growth and survival in bronchial smooth muscle. Vit. D exposure has the potential to skew cytokine expression from a Th1 (less allergic) to a Th2 (more allergic) phenotype. Due to their developmental immaturity, preterm infants may be particularly vulnerable to any positive or negative effects of vit. D supplementation on the lung, airway, and immune system. Our preliminary data, supported by the literature, suggests that overly aggressive vit. D supplementation may inadvertently increase wheezing in infancy in black, but not white, preterm infants; however, vit. D deficiency could theoretically also increase wheezing via vulnerability to respiratory pathogens. The proposed study is a randomized clinical trial comparing the effect of two different enteral vitamin D supplementation strategies on recurrent wheezing in infancy in 300 black infants born preterm at 28 0/7-36 6/7 wks gestational age, a population for whom neither vit. D requirements nor optimal vit. D serum levels have been established. The investigators will test two strategies: (I) sustained supplementation until 6 mo. of age adjusted for prematurity, and (II) cessation of supplementation when a minimum dietary intake of 200 IU/day is reached. The specific aims are to characterize the effect of each strategy on (aim 1) recurrent wheezing and (aim 2) allergic sensitization and atopy. The investigators will (aim 3) explore the relationship between vit. D serum levels and recurrent wheezing. The investigators hypothesize that strategy II will be more effective in promoting pulmonary health by minimizing recurrent wheezing, allergic sensitization, and overall healthcare utilization, and will be sufficient to prevent clinical vit. D deficiency. The investigators also hypothesize that optimal vit. D serum levels will be lower than the norms for other populations.

Conditions
Wheezing, Allergy
Being tested
Cholecalciferol
Medical subject headings
Respiratory Sounds, Hypersensitivity

What participants receive

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

  • CholecalciferolDietary supplement

    Once the dietary intake of vitamin D has exceeded 200 IU/Day, the infants will receive placebo until they are 6 months of age adjusted for prematurity

  • CholecalciferolDrug

    Also called D-Vi-Sol, Vitamin D

    Infants will receive cholecalciferol 400 IU/day PO until they are 6 months of age adjusted for prematurity

Study groups in NCT01601847
Study groupRoleWhat they receive
SustainedActive comparatorInfants will remain on 400 IU/day of cholecalciferol until 6 months of age adjusted for prematurity, regardless of dietary intake
Receives: Drug: Cholecalciferol
Diet-LimitedPlacebo comparatorInfants will receive placebo once their dietary intake of vitamin D has exceeded 200 IU/day
Receives: Dietary Supplement: Cholecalciferol

What is being measured

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

  1. Number of Infants With Recurrent Wheezing

    Recurrent wheezing was defined as more than 1 episode of wheezing reported during the study period. Separate episodes were defined as occurring at least 2 weeks apart.

    Measured: up to 12 months adjusted age

Secondary outcomes (2)

  1. Number With Infants With Allergic Sensitization as Measured by the PhadiaTop Infant Assay

    Measured using the Phadiatop Infant IgE panel

    Measured: Measured at the 12 month adjusted age visit

  2. Bone Density

    Measured by bone speed of sound (ultrasound)

    Measured: Measured at the 12 month adjusted age visit

Timeline

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

  1. First posted18 May 2012 (estimated)
  2. Study startJan 2013
  3. Primary completion12 Mar 2017
  4. Study completion12 Mar 2017

Resources

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 4
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
300 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01601847
Sponsor's protocol ID
R01HL109293
Other IDs
R01HL109293
Acronym
D-Wheeze
Status last verified
May 2018
First submitted
16 May 2012
Last updated
8 Jun 2018
Data monitoring committee
Yes

Publications

  • Benson AC, Chen Z, Minich NM, Tatsuoka C, Furman L, Ross K, Hibbs AM. Human milk feeding and wheeze in Black infants born preterm. J Perinatol. 2022 Nov;42(11):1480-1484. doi: 10.1038/s41372-022-01471-w. Epub 2022 Aug 4.

    PubMed 35927485

  • Huey SL, Acharya N, Silver A, Sheni R, Yu EA, Pena-Rosas JP, Mehta S. Effects of oral vitamin D supplementation on linear growth and other health outcomes among children under five years of age. Cochrane Database Syst Rev. 2020 Dec 8;12(12):CD012875. doi: 10.1002/14651858.CD012875.pub2.

    PubMed 33305842

  • Ledingham L, Tatsuoka C, Minich N, Ross KR, Kerns LA, Wagner CL, Fuloria M, Groh-Wargo S, Zimmerman T, Hibbs AM. Burden of prematurity-associated recurrent wheezing: caregiver missed work in the D-Wheeze trial. J Perinatol. 2021 Jan;41(1):69-76. doi: 10.1038/s41372-020-0729-7. Epub 2020 Jul 21.

    PubMed 32694857

  • Hibbs AM, Ross K, Kerns LA, Wagner C, Fuloria M, Groh-Wargo S, Zimmerman T, Minich N, Tatsuoka C. Effect of Vitamin D Supplementation on Recurrent Wheezing in Black Infants Who Were Born Preterm: The D-Wheeze Randomized Clinical Trial. JAMA. 2018 May 22;319(20):2086-2094. doi: 10.1001/jama.2018.5729.

    PubMed 29800180

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Cholecalciferol in people with Wheezing and Allergy, run by Case Western Reserve University at 5 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 5 inclusion and 12 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: finished, as of the sponsor's last update on 8 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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 8 Jun 2018). 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?

Number of Infants With Recurrent Wheezing (time frame: up to 12 months adjusted age). 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 NCT01601847, which also lists 4 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 8 Jun 2018.

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