- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01601847
Wheezing in Black Preterm Infants: Impact of Vitamin D Supplementation Strategy (D-Wheeze)
May 8, 2018 updated by: Anna Maria Hibbs, Case Western Reserve University
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.
Study Overview
Status
Completed
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
300
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
New York
-
New York, New York, United States, 10467
- Montefiore Medical Center
-
-
Ohio
-
Cleveland, Ohio, United States, 44109
- MetroHealth Medical Center
-
Cleveland, Ohio, United States, 44023
- Case Western Reserve University
-
Cleveland, Ohio, United States, 44023
- University Hospitals
-
-
South Carolina
-
Charleston, South Carolina, United States, 29425
- Medical University of South Carolina
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
No older than 1 year (Child)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion criteria:
- 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.
Exclusion criteria:
- 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;
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Sustained
Infants will remain on 400 IU/day of cholecalciferol until 6 months of age adjusted for prematurity, regardless of dietary intake
|
Infants will receive cholecalciferol 400 IU/day PO until they are 6 months of age adjusted for prematurity
Other Names:
|
Placebo Comparator: Diet-Limited
Infants will receive placebo once their dietary intake of vitamin D has exceeded 200 IU/day
|
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
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Infants With Recurrent Wheezing
Time Frame: up to 12 months adjusted age
|
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.
|
up to 12 months adjusted age
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number With Infants With Allergic Sensitization as Measured by the PhadiaTop Infant Assay
Time Frame: Measured at the 12 month adjusted age visit
|
Measured using the Phadiatop Infant IgE panel
|
Measured at the 12 month adjusted age visit
|
Bone Density
Time Frame: Measured at the 12 month adjusted age visit
|
Measured by bone speed of sound (ultrasound)
|
Measured at the 12 month adjusted age visit
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Anna Maria Hibbs, MD, MSCE, Case Western Reserve University
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
- 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.
- 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. Erratum In: JAMA. 2018 Aug 14;320(6):605.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
January 1, 2013
Primary Completion (Actual)
March 12, 2017
Study Completion (Actual)
March 12, 2017
Study Registration Dates
First Submitted
May 16, 2012
First Submitted That Met QC Criteria
May 17, 2012
First Posted (Estimate)
May 18, 2012
Study Record Updates
Last Update Posted (Actual)
June 8, 2018
Last Update Submitted That Met QC Criteria
May 8, 2018
Last Verified
May 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- R01HL109293 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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