Vitamin C Supplementation to Pregnant Smokers: Follow-up of 2 Randomized Trials Plus Changes in DNA Methylation

Asthma Clinical Trial

— VCSIP-ECHO  

Official title:

Maternal Vitamin C Supplementation to Decrease Effects of Smoking During Pregnancy on Infant Lung Function and Health: Follow-up of 2 Randomized Trials and Association With Changes in DNA Methylation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03206710
• Other study ID #: VCSIP ECHO
• Secondary ID: UG3OD023288
• Status: Recruiting
• Start date: June 1, 2017
• Est. completion date: December 1, 2024

Study information

• Verified date: April 2024
• Source: Oregon Health and Science University
• Contact: Cindy McEvoy, MD, MCR
• Phone: 503-494-0085
• Email: mcevoyc[@]ohsu.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

In a randomized clinical trial (RCT) published in JAMA, the investigators have provided evidence that vitamin C supplementation (500 mg daily during pregnancy) ameliorates the effects of maternal smoking during pregnancy on offspring lung function and subsequent incidence of wheeze by 48% through 1 year of age. The investigators are currently completing a second RCT of vitamin C supplementation in pregnant smokers with more robust measures of pulmonary outcomes. The purpose of this ECHO application is to combine these 2 focused, interventional cohorts to allow critical longitudinal follow-up of respiratory outcomes in these children including the study of pulmonary function test (PFT) trajectories and incidence of recurrent wheeze/asthma from infancy through early adolescence in offspring of pregnant smokers randomized to vitamin C versus placebo.

Description:

In a randomized clinical trial (RCT) published in JAMA, the investigators have provided evidence that vitamin C supplementation (500 mg daily during pregnancy) ameliorates the effects of maternal smoking during pregnancy on offspring lung function and subsequent incidence of wheeze by 48% through 1 year of age. the investigators are currently completing a second RCT of vitamin C supplementation in pregnant smokers with more robust measures of pulmonary outcomes. The purpose of this ECHO application is to combine these 2 focused, interventional cohorts to allow critical longitudinal follow-up of respiratory outcomes in these children including the study of pulmonary function test (PFT) trajectories and incidence of recurrent wheeze/asthma from infancy through early adolescence in offspring of pregnant smokers randomized to vitamin C versus placebo.

This will allow the investigators to study the duration of the protection vitamin C provides in the face of in-utero smoke, the relationship between PFTs and the development of recurrent wheeze and/or asthma. In addition we have preliminary data suggesting that, in parallel with the effects of vitamin C on the reduction of pulmonary harm, the supplementary vitamin C blocked the majority of significant changes in DNA methylation induced by maternal smoking in placentas, cord blood and offspring cheek cells. Thus this study will also study the association between the prevention of wheeze/asthma associated with maternal smoking during pregnancy and the prevention of epigenetic changes caused by maternal smoking during pregnancy. By linking the clinical outcomes of decreased wheeze/asthma and pulmonary function in offspring of smokers to epigenetic changes, this study has the potential to identify genes linked to the effects of maternal smoking on lung development and the protective effects of vitamin C.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 420
• Est. completion date: December 1, 2024
• Est. primary completion date: December 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 11 Years

Eligibility

Inclusion Criteria:

• Women and their offspring randomized to vitamin C versus placebo during pregnancy in VCSIP1 or VCSIP2 as well as pregnant nonsmokers and their offspring enrolled as the reference group in VCSIP 1 or VCSIP2

Exclusion Criteria:

• Patients specifically withdrawing consent from VCSIP1 or VCSIP2

Related Conditions & MeSH terms

• Asthma
• In Utero Nicotine
• Pulmonary Function
• Respiratory Sounds
• Wheezing

Intervention

Other:
• No current intervention
This is a follow-up of two randomized trials. No active intervention is being given in the follow-up

Locations

Country	Name	City	State
United States	Indiana University	Indianapolis	Indiana
United States	Oregon Health and Science University	Portland	Oregon

Sponsors (3)

Lead Sponsor	Collaborator
Oregon Health and Science University	Indiana University, National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (1)

McEvoy CT, Schilling D, Clay N, Jackson K, Go MD, Spitale P, Bunten C, Leiva M, Gonzales D, Hollister-Smith J, Durand M, Frei B, Buist AS, Peters D, Morris CD, Spindel ER. Vitamin C supplementation for pregnant smoking women and pulmonary function in thei — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improved pulmonary function	The first primary aim of this study is to demonstrate improved pulmonary function trajectories as measured with forced expiratory flows through 15 years of age in the offspring of pregnant smokers randomized to vitamin C (500 mg/day) versus placebo.	through 15 years of age
Primary	Decreased recurrent wheeze/asthma	The second primary aim of this study is to demonstrate a decreased incidence of recurrent wheeze/ asthma through 15 years of age in the offspring of pregnant smokers randomized to vitamin C (500 mg/day) versus placebo.	through 15 years of age
Secondary	Decreased incidence of recurrent wheeze/asthma	A secondary aim of this study is to demonstrate a decreased incidence of recurrent wheeze/asthma through 15 years of age in offspring of pregnant smokers randomized to vitamin C (500 mg/day) versus placebo	through 15 years of age
Secondary	Epigenetic changes	An additional secondary aim of the study is the analysis of epigenetic changes caused by maternal smoking and reversed by vitamin C at birth. DNA methylation will be measured in biologic samples and then followed longitudinally through ages 15.	through 15 years of age