Vitamin D Supplementation During Pregnancy for Prevention of Asthma in Childhood

Asthma Clinical Trial

— ABCvitaminD  

Official title:

Vitamin D Supplementation During Pregnancy for Prevention of Asthma in Childhood: An Interventional Trial in the ABC (Asthma Begins in Childhood) Cohort

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00856947
• Other study ID #: 2008-007871-26
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: March 2009
• Est. completion date: July 2027

Study information

• Verified date: April 2023
• Source: Copenhagen Studies on Asthma in Childhood
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 600
• Est. completion date: July 2027
• Est. primary completion date: July 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Asthma

Intervention

Dietary Supplement:
• Cholecalciferol D3
2 tablets of 1200 IU daily from week 24 of gestation to 1 week after delivery

Other:
• Placebo tablet
2 tablets containing no active substance

Locations

Country	Name	City	State
Denmark	Copenhagen University Hospital of Copenhagen	Gentofte
Denmark	Næstved Hospital, Pediatric Department	Næstved

Sponsors (1)

Lead Sponsor	Collaborator
Copenhagen Studies on Asthma in Childhood

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Asthma	Asthma diagnosed from age 3 to 10 years based on the same predefined algorithm of recurrent troublesome lung symptoms, response to treatment after withdrawal of treatment, which was used for persistent wheeze at age 0-3 in phase 1 of the study. Primary outcome in phase 2 is current asthma at specific visits till age 10 years, which is diagnosed in children fulfilling the persistent wheeze algorithm at any point during the first 10 years of life and still needing inhaled corticosteroids at specific visits (3, 4, 5, 6, 8 and 10 years of age) to control the symptoms.	3-10 years of age
Other	Lung function measurements	Spirometry measuring airflow assessed by FEV1, MMEF and FEV1/FVC ratio at age 5, 6, 8 and 10 years.	5-10 years of age
Other	Infections	Prescribed medicine for infections. Types and length of infections	3-10 years of age
Other	Growth	Anthropometrics: Clinical follow up on the development of weight in kg (calibrated digital weight scales), height in cm (Harpenden stadiometer), waist-, thorax- and head circumference in cm (using tape; 3 times each) at every visit till age 10 years assessed longitudinally in the research clinic.	3- 10 years of age
Other	Eczema	Age at onset of eczema diagnosed prospectively by research doctors according to predefined algorithm based upon Hanifin and Rajka criteria	3-10 years of age
Other	Allergic sensitization/atopy	Allergic sensitization at 6 and 10 years of age assessed by skin prick test (ALK-Abelló, Denmark) and specific IgE in blood (ImmunoCAP, PHarmacia Diagnostics AB, Sweden).	6-10 years of age
Other	Airway mucosal immune status	Immune status measured in airway mucosal lining fluid at 3, 6 and 10 years of age (combined assessments by principal component analyses for each age point).	3-10 years of age
Other	The diagnose allergic rhinitis	Allergic rhinitis will be diagnosed by combining allergic sensitization with symptom recording of troublesome congestion or sneezing or runny nose upon relevant exposure to allergens at age 3, 4, 5, 6, 8 and 10 years.	3-10 years of age
Other	Asthma exacerbations:	Age at onset and number of severe asthma exacerbation diagnosed by predefined criteria of acute severe asthma requiring oral/ high dose inhaled steroids or acute hospital contact	3-10 years of age
Other	Airway resistance	Measured by plethysmography (sRaw) at age 3, 4, 5, 6, 8 and 10 years.	3-10 years of age
Other	Airway resistance	Multiple breath wash-out using SF6 and N2 as inert gasses to determined LCI, Scond and Sacin at ages 3, 4 and 5 years.	3-5 years of age
Other	Bronchial reactivity:	Provocative dose of methacholine leading to a 20% drop in FEV1 from baseline (PD20 value) at age 6 years.	at 6 years of age
Other	Body composition	Body composition measured as fat mass, lean mass, bone mineral content (BMC) and bone mineral density assessed (BMD) through DXA scans at 3 and 6 years of age.; Body impedance measurements at 10 years of age.	3-10 years of age
Other	Airway inflammation:	Measurement of fractional exhaled nitric oxide (FeNO) at age 6, 8 and 10 years	6-10 years of age
Other	Cognitive function	A 2,5 hours cognitive evaluation at 10 years of age. Cognitive functions from a broad spectrum of cognitive domains will be assessed with subtests both using paper pencil tests and Cambridge Neuropsychological Test Automated Battery .	10 years of age
Other	MRI scanning of the Brain	MRI scanning of the Brain	10 years of age
Other	Behavioral and psychopathological dimensions.	Questionnaires will be administered to the parents.	6- 10 years of age
Other	Behavioral and psychopathological dimensions.	Behavioral and psychopathological dimensions will be assessed at 10 years of age.; The childrens' potential psychiatric diagnoses will be ascertained through the semi-structured clinical interview Schedule for Affective Disorders and Schizophrenia for School-Age Children - Present and Lifetime Version (K-SADS-PL) first with a parent and next with the child.	10 years of age
Other	Strength and Difficulties Questionnaire (SDQ)- Questionnaires	The Strengths and Difficulties Questionnaire (SDQ) is a brief behavioural screening questionnaire about 3-16 year olds. Questionnaires will be administered to the parents to obtain their evaluation of their child's potential psychopathology and behavior problems. Scores will be calculated form the questionnaires in order validated methods	6, 8 and 10 years of age
Other	ADHD- RS- Questionnaires	The ADHD Rating Scale obtains parent ratings regarding the frequency of each ADHD symptom based on DSM criteria.; Questionnaires will be administered to the parents to obtain their evaluation of their child's potential psychopathology and behavior problems. Scores will be calculated form the questionnaires. Scores will be calculated form the questionnaires in order validated methods.	8 and 10 years of age
Other	Social Responsive Scale, Second version (SRS-2)	The SRS-2 identifies social impairment associated with autism spectrum disorders (ASDs) and quantifies its severity Questionnaires will be administered to the parents to obtain their evaluation of their child's potential psychopathology. Scores will be calculated form the questionnaires. Scores will be calculated form the questionnaires in order validated methods.	10 years of age
Other	The Child Behavior Checklist school-age version (CBCL)	The Child Behavior Checklist (CBCL) is a widely used questionnaire to assess behavioral and emotional problems.; Questionnaires will be administered to the parents to obtain their evaluation of their child's potential psychopathology and behavior problems. Scores will be calculated form the questionnaires. Scores will be calculated form the questionnaires in order validated methods.	10 years of age
Other	The Behavior Rating Inventory of Executive Function 2nd edition (BRIEF-2)	The BRIEF-2 is a set of questionnaires for parents and teachers , designed to evaluate executive function from multiple perspectives.; Questionnaires will be administered to the parents to obtain their evaluation of their child's potential psychopathology. Scores will be calculated form the questionnaires. Scores will be calculated form the questionnaires in order validated methods.	10 years of age
Primary	Persistent wheeze	Age at onset of persistent wheeze diagnosed according to predefined algorithm of recurrent troublesome lung symptoms, response to treatment and relapse after withdrawal of treatment	0 to 3 years of age
Secondary	Infections	Main analysis: • Number of lower respiratory tract infections registered in daily diaries; Secondary analyses: Acute otitis media; Number of upper respiratory tract infections; Number of other infections; Total number of infections	0 to 3 years of age
Secondary	Allergic sensitization	Allergic sensitization at 6 and/or 18 months assessed by skin prick test and specific IgE in blood	6 and 18 months of age
Secondary	Eczema	Age at onset of eczema diagnosed prospectively by research doctors according to predefined algorithm based upon Hanifin and Rajka criteria	0 to 3 years of age
Secondary	Mothers levels of 25-OH-Vitamin D, PTH, Calcium, alkaline phosphatase		1 week after delivery
Secondary	Growth		0 to 3 years of age
Secondary	Asthma exacerbations	Age at onset of severe asthma exacerbation diagnosed by predefined criteria of acute severe asthma requiring oral/high dose inhaled steroids or acute hospital contact	0 to 3 years of age
Secondary	Neurological development	Main analysis: • Cognitive development assessed at 2½ years using the cognitive part of Bayley Scales of Infant and Toddler Development, third edition; Secondary analyses: Milestone development monitored prospectively by the parents using a registration form based on The Denver Development Index and WHO milestones registration (combined assessment by principal component analysis); Language development assessed at 1 and 2 years of age with the Danish version of The MacArthur Bates Communicative Developmental Inventory (CDI); The child´s general development (language, fine and gross motor, social and problem solving) at 3 years of age assessed with Ages and stages Questioner, third edition (ASQ-3)	0-3 years
Secondary	Growth	Main analysis: • Body composition (fat mass and bone mineral density) assessed by DEXA scan at 3 years of age; Secondary analysis; • Development of BMI from birth to 3 years assesses longitudinally in the research clinic	0-3 years
Secondary	Systemic immune status	Main analysis Immune status at 18 months measured in stimulated whole blood as cytokine release (combined assessments by prinicipal component analyses); Secondary analyses Composition of immune cell subsets in whole blood at birth and at 18 months of age	18 months
Secondary	Airway mucosal immune status	Immune status measured in airway mucosal lining fluid at 4 weeks and 2 years of age (combined assessments by prinicipal component analyses for each age point)	4 weeks and 2 years
Secondary	17q21 genotype and sphingolipid metabolites	In a secondary analyses, we will determine the effect of 17q21 genotype on the efficacy of vitamin D supplementation in the prevention of asthma/wheeze. We will compute hazard ratios for the reduction in asthma/wheeze risk associated with prenatal supplementation, stratified by rs12936231. rs12936231 is a functional SNP influencing expression of ORMDL3, and given the role of ORMDL3 as a key sphingolipid biosynthesis regulator, we will subsequently investigate the relative abundance of sphingolipids between those in the vitamin D Intervention arm and those in the placebo group, stratified by 17q21 genotype. Finally we will identify interactions between prenatal vitamin D supplementation, rs12936231 genotype and sphingolipid metabolism in the risk of asthma/wheeze by age three.	6 months
Secondary	Dental health	Caries and enamel defects (molar incisor hypomineralization, MIH) determined at a dental examination at age 6 years.	6 year