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Randomized Trial: Maternal Vitamin D Supplementation to Prevent Childhood Asthma (VDAART) (VDAART)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Scott T. Weiss, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT00920621
First received: June 11, 2009
Last updated: July 12, 2017
Last verified: July 2017
June 11, 2009
July 12, 2017
September 2009
January 21, 2015   (Final data collection date for primary outcome measure)
  • Asthma or Recurrent Wheeze in First 3 Years of Life [ Time Frame: First 3 years of life. ]

    Parental report of physician diagnosis of asthma or occurrence of recurrent wheeze in the child's first 3 years of life ascertained from questionnaires administered every 3 months.

    *For some variables the "negative" count incorporates "negative and indeterminate."

  • Achieved Maternal 25(OH)D Level of ≥ 30 ng/mL at Third Trimester Sampling. [ Time Frame: 32-38 weeks gestation ]
    Maternal serum 25-hydroxyvitamin D measurement at third trimester during pregnancy
Asthma or recurrent wheeze in the child. [ Time Frame: 1 year and 3 years ]
Complete list of historical versions of study NCT00920621 on ClinicalTrials.gov Archive Site
  • Child Positive-specific IgE Tests From Blood Collection at 3 Year Visit. [ Time Frame: 3 years ]
    Child positive-specific IgE tests from blood collection at 3 year visit.
  • Child Serum 25-hydroxyvitamin D Measurement From Blood Collection at 1 Year Visit. [ Time Frame: 1 year visit ]
    Child serum 25-hydroxyvitamin D measurement from blood collection at 1 year visit.
  • Parental Report of Physician Diagnosed Eczema (With Rash) in the Child's First 3 Years of Life. [ Time Frame: Child's first 3 years of life. ]

    Parental report of physician diagnosis of eczema with rash in typical distribution in the child's first 3 years of life ascertained from questionnaires administered every 3 months.

    *For some variables the "negative" count incorporates "negative and indeterminate."

  • Parental Report of Physician Diagnosis of Lower Respiratory Tract Infection in the Child's First 3 Years of Life. [ Time Frame: Child's first 3 years of life. ]
    Parental report of physician diagnosis of lower resperatory tract infection (LRI) in the child's first 3 years of life. LRI defined as physician diagnosed bronchitis, bronchiolitis, croup, or pneumonia ascertained from questionnaires administered every 3 months.
  • Child Serum 25-hydroxyvitamin D Measurement From Blood Collection at 3 Year Visit. [ Time Frame: Blood collection at childs' 3 year visit. ]
    Child serum 25-hydroxyvitamin D measurement from blood collection at 3 year visit.
  • Any Allergic Sensitization in the Child's First 3 Years of Life. [ Time Frame: Child's first 3 years of life. ]

    Any allergic sensitization in the child's first 3 years of life.

    *For some variables the "negative" count incorporates "negative and indeterminate."

  • Mass Spec Vitamin D Value From Cord Blood at Delivery [ Time Frame: Blood collection at delivery ]
    Mass Spec Vitamin D value from cord blood at delivery
Not Provided
Not Provided
Not Provided
 
Randomized Trial: Maternal Vitamin D Supplementation to Prevent Childhood Asthma (VDAART)
Randomized Trial: Maternal Vitamin D Supplementation to Prevent Childhood Asthma (VDAART)
Vitamin D supplementation given to pregnant women will prevent asthma in their offspring and children.

Asthma is one of the leading causes of morbidity in children with 60% of all cases diagnosed by age 3. Thus, finding factors that can lead to prevention of this disease would be of great public health importance. Vitamin D deficiency is highly prevalent among pregnant women, and thus, represents a potentially modifiable factor for the prevention of disease. Due to the effect of vitamin D in modulating immune responses, we believe that vitamin D deficiency in pregnant mothers leads to faulty immune system development in the neonate, predisposing them to asthma and allergy. We have observational data from two independent birth cohort studies that higher maternal intakes of vitamin D during pregnancy are each independently associated with a 50% reduction in risk for recurrent wheezing and asthma in 3- and 5-yr old children. However, in order to recommend this as a universal treatment to prevent asthma, a randomized, controlled, clinical trial is necessary. Therefore, we propose a two arm, double-blind, placebo controlled, randomized, clinical trial of Vitamin D, to determine whether higher vitamin D intake and levels in the pregnant mother will prevent asthma and allergy in the child at age 3. We will identify pregnant women who have asthma or allergies or whose partner has asthma or allergies, from obstetric clinics in the three clinical centers participating in this trial. We will recruit 870 pregnant women during the first trimester of pregnancy and randomize them to one of two treatment arms of a 4-year clinical trial: 4000 IU of Vitamin D in addition to usual prenatal vitamins, n=435; and usual prenatal vitamins alone, n=435. Our primary specific aim is to determine whether adequate vitamin D supplementation in the pregnant mother is associated with reduced incidence of asthma in the child during the first 3 years of life. The sub-aims of the study will include (1) To determine whether adequate vitamin D supplementation in the pregnant mother is associated with reduced secondary outcomes in the child of (a) allergic sensitization, (b) doctor's diagnosis of eczema and (c) lower respiratory tract infections during the first 3 years of life; and (2) To determine whether adequate vitamin D supplementation in the pregnant mother is associated with improved vitamin D status in the mothers and their offspring through measurement of 25(OH)D levels in maternal plasma, cord blood, and children's blood at 1 and 3 yrs of age and (3)To determine whether sufficient vitamin D supplementation in the pregnant mother is associated with reduced incidence of preterm birth (birth <37 weeks gestation), preeclampsia, gestational hypertension, and/or Hemolytic anemia, Elevated Liver enzymes, Low Platelet count (HELLP syndrome) (PB/PE) compared to a usual care control group in VDAART.

VDAART Analysis Plan (Addendum to Protocol)

All analyses of primary and secondary outcomes stated in the VDAART Protocol will be performed using the intent-to-treat (ITT) paradigm, unless specifically stated.

I. Definition of outcomes.

A. Asthma and recurrent wheezing. The primary outcome of the trial will be development of a doctor's diagnosis of asthma and/or recurrent wheeze. While asthma is acknowledged to have its roots in early life, making a definite diagnosis is difficult until the child is older, and wheezing illnesses may be precursors of an asthma diagnosis. Thus, we will have a composite definition for the primary outcome.

  • Asthma will be defined as a parent's report of physician's diagnosis at any time during the first three years of life, based on questionnaire responses. For time-to-event analyses, the time of incident asthma will be determined by the time of first positive questionnaire response.
  • Recurrent wheezing will be defined as at least one report of wheezing in the third year of life plus any report of wheezing in any of the first two years of life.

Recognizing that wheezing symptoms may be modified by medication use, variable age of onset, and other variables, the following will be included in the composite outcome:

  • children who had at least one wheezing episode (during the 1st 2 years of life), plus an asthma controller medication (defined as steroid inhalers or nebulizers OR steroid pills or liquids OR leukotriene modifiers) in the third year
  • children who did not report any wheezing in the first 2 years but who report 2 separate episodes of wheezing in the third year OR are on controller medication (defined as above) on at least 2 separate reports in the third year OR at least 1 report of wheezing and at least 1 separate report of controller medication use in the third year

For recurrent wheezing (and the other wheezing phenotypes), the time of incident recurrent wheezing will be determined by the time of first report of wheezing, for time-to-event analyses. In the event that the child meets the definition based solely on the use of controller medication, the first report of use of this controller medication will be used to determine the time of onset of wheezing for time-to-event analyses.

For these outcomes, because the questions were asked every 3 months, and recognizing that missing questionnaires occurred, event times will be treated as interval-censored.

B. Eczema. Eczema will be defined as a positive response to parent's report of physician's diagnosis at any time during the first three years of life based on the questionnaire responses.

C. Lower respiratory tract infections (LRI). Lower respiratory tract infections (LRIs) will be defined based on parental responses to questionnaires. LRIs will be defined as a parental report of a physician's diagnosis of pneumonia, bronchiolitis, bronchitis, or croup (laryngotracheobronchitis). LRIs may occur multiple times over a three-year period in a child. Information on repeated episodes of LRI will be employed for rate estimation and comparison.

D. Total and specific IgE. Total and specific serum IgE will be measured from cord blood samples, and from year 3 samples from the children. Total IgE will be analyzed as a continuous outcome. Sensitization will be defined as any specific IgE ≥ 0.35 IU.

II. Secondary Analyses.

A. Analyses based on levels. Secondary analyses using baseline and follow-up maternal 25OHD levels will be performed. We will investigate the effect of baseline and follow-up maternal levels separately on the development of primary and secondary outcomes in the trial. Additionally, we will categorize mothers into categories based on joint baseline and follow-up levels. Mothers who have baseline levels and follow-up levels ≥ 40 mg/dl will be categorized in the HI-HI group; those who have baseline levels and follow-up levels < 40 mg/dl will be categorized in the LO-LO group; mothers who do not meet these definitions will be categorized either in the HI-LO or LO-HI groups based on their baseline and follow-up levels.

B. We also performed metabolomics on the children at age 1 and 3 and eventually age 6. We are assessing the association with vitamin D, asthma, and other phenotypes such as food allergies, IgE, and lung function with metabolites and genetic variants.

C. As an ancillary study, we have collected stool samples from the mothers in the 3rd trimester, and samples from the infants and children at 3-6 months, 1 year, and 3 years. We will sequence the stool samples for the microbiome, and we will assess the effects of the early life microbiome on the development of asthma, allergies (including food allergies and sensitization), growth and development, and obesity.

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Asthma
  • Dietary Supplement: Vitamin D 3 cholecalciferol
    Dosage form oral Dosage 4000IU Vitamin D 3 cholecalciferol
    Other Names:
    • vitamin D
    • vitamin D3
    • cholecalciferol
  • Dietary Supplement: Vitamin D3
    4000 IU of vitamin D3 administered orally once a day during pregnancy
  • Experimental: Vitamin D treatment
    vitamin D treatment plus prenatal multivitamins
    Interventions:
    • Dietary Supplement: Vitamin D 3 cholecalciferol
    • Dietary Supplement: Vitamin D3
  • Placebo Comparator: placebo
    placebo plus prenatal multivitamins
    Intervention: Dietary Supplement: Vitamin D3

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
876
June 2019
January 21, 2015   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Personal history of asthma, eczema, allergic rhinitis or a history of asthma, eczema, allergic rhinitis in the biological father of the child
  • Gestational age between 10 and 18 weeks at the time of randomization
  • Maternal age between 18 and 39 years
  • Not a current smoker
  • English or Spanish speaking
  • Intent to participate for the full 4 years (through Pregnancy and then until the 3rd birthday of the child)

Exclusion Criteria:

  • Not meeting inclusion criteria
  • Gestational age greater than 18 weeks
  • Presence of chronic medical conditions
  • Taking vitamin D supplements containing more than 2000 IU/day of vitamin D3
  • Multiple gestation pregnancy (twins, triplets)
  • Pregnancy achieved by assisted reproduction techniques (e.g., IUI, IVF)
Sexes Eligible for Study: Female
18 Years to 39 Years   (Adult)
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00920621
655
5U01HL091528-03 ( U.S. NIH Grant/Contract )
HL091528-01A1
Yes
Not Provided
Not Provided
Scott T. Weiss, Brigham and Women's Hospital
Brigham and Women's Hospital
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Scott T Weiss Brigham and Women's Hospital
Brigham and Women's Hospital
July 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP