SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT00856947

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

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

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.

NCT00856947 Asthma
MeSH: Asthma
HPO: Asthma

2 Interventions

Name: Cholecalciferol D3

Description: 2 tablets of 1200 IU daily from week 24 of gestation to 1 week after delivery

Type: Dietary Supplement

Vitamin D

Name: Placebo tablet

Description: 2 tablets containing no active substance

Type: Other

Placebo


Primary Outcomes

Description: 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

Measure: Persistent wheeze

Time: 0 to 3 years of age

Secondary Outcomes

Description: 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

Measure: Infections

Time: 0 to 3 years of age

Description: Allergic sensitization at 6 and/or 18 months assessed by skin prick test and specific IgE in blood

Measure: Allergic sensitization

Time: 6 and 18 months of age

Description: Age at onset of eczema diagnosed prospectively by research doctors according to predefined algorithm based upon Hanifin and Rajka criteria

Measure: Eczema

Time: 0 to 3 years of age

Measure: Mothers levels of 25-OH-Vitamin D, PTH, Calcium, alkaline phosphatase

Time: 1 week after delivery

Measure: Growth

Time: 0 to 3 years of age

Description: 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

Measure: Asthma exacerbations

Time: 0 to 3 years of age

Description: 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)

Measure: Neurological development

Time: 0-3 years

Description: 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

Measure: Growth

Time: 0-3 years

Description: 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

Measure: Systemic immune status

Time: 18 months

Description: 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)

Measure: Airway mucosal immune status

Time: 4 weeks and 2 years

Description: 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.

Measure: 17q21 genotype and sphingolipid metabolites

Time: 6 months

Description: Caries and enamel defects (molar incisor hypomineralization, MIH) determined at a dental examination at age 6 years.

Measure: Dental health

Time: 6 year

Purpose: Prevention

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 rs12936231

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.. Dental health.



HPO Nodes


HPO:
Asthma
Genes 66
ELOVL4 FLG COL5A1 LIFR COL5A2 TGIF1 LIG4 CDSN ERCC2 BCL11B CARMIL2 COMT SEC24C ALMS1 ARVCF NKX2-1 DOCK8 GLI2 TRAIP NFKB2 CFTR TBX21 SCN4A UFD1 GAS1 PEPD SHH BBS1 GTF2H5 PEX5 CASP8 FGF8 CARD11 FGFR1 TDGF1 PLCG2 LRBA SIK3 COX4I2 IDS PTCH1 RREB1 FOXH1 SIX3 DLL1 ADA SUFU NODAL NSUN2 GRHL2 TALDO1 NEK9 CCDC151 JMJD1C DISP1 TBX1 PGM3 SDHD CDON HIRA ZIC2 GP1BA GP1BB COL1A1 SPINK5 GP9