Clinical trial NCT00856947: Vitamin D Supplementation During Pregnancy for Prevention of Asthma in Childhood
Official title: Vitamin D Supplementation During Pregnancy for Prevention of Asthma in Childhood: An Interventional Trial in the ABC (Asthma Begins in Childhood) Cohort
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Asthma
Keywords: wheeze
infections
allergy
eczema
vitamin D
Lead sponsor: Copenhagen Studies on Asthma in Childhood
Sponsor class: OTHER
First posted: 2009-03-06
Enrollment: 600
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The aim of this study is to prevent asthma symptoms (recurrent wheeze) in childhood by supplementation with high dose vitamin D to the mother during pregnancy. Participants are mothers and children of the ABC (Asthma Begins in Childhood) cohort. Mothers are recruited during pregnancy and receive daily supplement with 2400 IU of Vitamin D3 or placebo from week 24 og gestation to 1 week after delivery. In addition all mothers are advised to take the recommended dose of 400 IU vitamin D daily. The mothers in ABC also participate in an interventional trial with fish oil supplementation, and the vitamin D randomization is stratified by fish oil treatment group. The child is followed with acute and planned vits at the research unit, and wheeze is diagnosed according to predefined algorithms.


Eligibility criteria: Inclusion Criteria:

Mother:

* Pregnant in week 22-26 of gestation
* Participating in the ABC-cohort
* Living in Sealand, Denmark
* Fluent in Danish
* Willing to let the child participate in the study

Exclusion Criteria:

Mother:

* Intake of more than 400 IU of vitamin D during the last 6 months
* Endocrinological disease such as calcium metabolic disorder, parathyroid disorder, thyroid disorder or Diabetes type 1
* Tuberculosis
* Sarcoidosis
* In need of diuretics or heart medication including calcium channel blockers

Primary outcomes:
measure: Persistent wheeze
timeFrame: 0 to 3 years of age
Secondary outcomes:
measure: Infections
timeFrame: 0 to 3 years of age
measure: Allergic sensitization
timeFrame: 6 and 18 months of age
measure: Eczema
timeFrame: 0 to 3 years of age
measure: Mothers levels of 25-OH-Vitamin D, PTH, Calcium, alkaline phosphatase
timeFrame: 1 week after delivery
measure: Growth
timeFrame: 0 to 3 years of age
measure: Asthma exacerbations
timeFrame: 0 to 3 years of age
measure: Neurological development
timeFrame: 0-3 years
measure: Growth
timeFrame: 0-3 years
measure: Systemic immune status
timeFrame: 18 months
measure: Airway mucosal immune status
timeFrame: 4 weeks and 2 years
measure: 17q21 genotype and sphingolipid metabolites
timeFrame: 6 months
measure: Dental health
timeFrame: 6 year
Other outcomes:
measure: Asthma
timeFrame: 3-10 years of age
measure: Lung function measurements
timeFrame: 5-10 years of age
measure: Infections
timeFrame: 3-10 years of age
measure: Growth
timeFrame: 3- 10 years of age
measure: Eczema
timeFrame: 3-10 years of age
measure: Allergic sensitization/atopy
timeFrame: 6-10 years of age
measure: Airway mucosal immune status
timeFrame: 3-10 years of age
measure: The diagnose allergic rhinitis
timeFrame: 3-10 years of age
measure: Asthma exacerbations:
timeFrame: 3-10 years of age
measure: Airway resistance
timeFrame: 3-10 years of age
measure: Airway resistance
timeFrame: 3-5 years of age
measure: Bronchial reactivity:
timeFrame: at 6 years of age
measure: Body composition
timeFrame: 3-13 years of age
measure: Airway inflammation:
timeFrame: 6-10 years of age
measure: Cognitive function
timeFrame: 10 years of age
measure: MRI scanning of the Brain
timeFrame: 10 years of age
measure: Behavioral and psychopathological dimensions.
timeFrame: 6- 10 years of age
measure: Behavioral and psychopathological dimensions.
timeFrame: 10 years of age
measure: Strength and Difficulties Questionnaire (SDQ)- Questionnaires
timeFrame: 6, 8 and 10 years of age
measure: ADHD- RS- Questionnaires
timeFrame: 8 and 10 years of age
measure: Social Responsive Scale, Second version (SRS-2)
timeFrame: 10 years of age
measure: The Child Behavior Checklist school-age version (CBCL)
timeFrame: 10 years of age
measure: The Behavior Rating Inventory of Executive Function 2nd edition (BRIEF-2)
timeFrame: 10 years of age
measure: Bone fractures
timeFrame: 0-13 years of age
Locations:
city: Gentofte
country: Denmark
facility: Copenhagen University Hospital of Copenhagen
city: Næstved
country: Denmark
facility: Næstved Hospital, Pediatric Department
Study officials:
affiliation: Copenhagen Studies on Asthma in Childhood
name: Klaus Bønnelykke, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mohammadzadeh P, Rosenberg JB, Vinding R, Mollegaard Jepsen JR, Lindberg U, Folsgaard N, Erlang Sorensen M, Sulaiman D, Bilenberg N, Mitta Raghava J, Fagerlund B, Vestergaard M, Pantelis C, Stokholm J, Chawes B, Larsson H, Glenthoj BY, Bonnelykke K, Ebdrup BH, Bisgaard H. Effects of prenatal nutrient supplementation and early life exposures on neurodevelopment at age 10: a randomised controlled trial - the COPSYCH study protocol. BMJ Open. 2022 Feb 1;12(2):e047706. doi: 10.1136/bmjopen-2020-047706.
citation: Knihtila HM, Kelly RS, Brustad N, Huang M, Kachroo P, Chawes BL, Stokholm J, Bonnelykke K, Pedersen CT, Bisgaard H, Litonjua AA, Lasky-Su JA, Weiss ST. Maternal 17q21 genotype influences prenatal vitamin D effects on offspring asthma/recurrent wheeze. Eur Respir J. 2021 Sep 23;58(3):2002012. doi: 10.1183/13993003.02012-2020. Print 2021 Sep.
citation: Sass L, Vinding RK, Stokholm J, Bjarnadottir E, Noergaard S, Thorsen J, Sunde RB, McGrath J, Bonnelykke K, Chawes B, Bisgaard H. High-Dose Vitamin D Supplementation in Pregnancy and Neurodevelopment in Childhood: A Prespecified Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2020 Dec 1;3(12):e2026018. doi: 10.1001/jamanetworkopen.2020.26018.
citation: Brustad N, Garland J, Thorsen J, Sevelsted A, Krakauer M, Vinding RK, Stokholm J, Bonnelykke K, Bisgaard H, Chawes BL. Effect of High-Dose vs Standard-Dose Vitamin D Supplementation in Pregnancy on Bone Mineralization in Offspring Until Age 6 Years: A Prespecified Secondary Analysis of a Double-Blinded, Randomized Clinical Trial. JAMA Pediatr. 2020 May 1;174(5):419-427. doi: 10.1001/jamapediatrics.2019.6083.
citation: Norrisgaard PE, Haubek D, Kuhnisch J, Chawes BL, Stokholm J, Bonnelykke K, Bisgaard H. Association of High-Dose Vitamin D Supplementation During Pregnancy With the Risk of Enamel Defects in Offspring: A 6-Year Follow-up of a Randomized Clinical Trial. JAMA Pediatr. 2019 Oct 1;173(10):924-930. doi: 10.1001/jamapediatrics.2019.2545.
citation: Wolsk HM, Chawes BL, Litonjua AA, Hollis BW, Waage J, Stokholm J, Bonnelykke K, Bisgaard H, Weiss ST. Prenatal vitamin D supplementation reduces risk of asthma/recurrent wheeze in early childhood: A combined analysis of two randomized controlled trials. PLoS One. 2017 Oct 27;12(10):e0186657. doi: 10.1371/journal.pone.0186657. eCollection 2017.
citation: Chawes BL, Bonnelykke K, Stokholm J, Vissing NH, Bjarnadottir E, Schoos AM, Wolsk HM, Pedersen TM, Vinding RK, Thorsteinsdottir S, Arianto L, Hallas HW, Heickendorff L, Brix S, Rasmussen MA, Bisgaard H. Effect of Vitamin D3 Supplementation During Pregnancy on Risk of Persistent Wheeze in the Offspring: A Randomized Clinical Trial. JAMA. 2016 Jan 26;315(4):353-61. doi: 10.1001/jama.2015.18318.