Vitamin C to Decrease Effects of Smoking in Pregnancy on Infant Lung Function (VCSIP) Longer Term Follow Up

Sponsor

Oregon Health and Science University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06106646

Collaborator

Indiana University (Other), National Heart, Lung, and Blood Institute (NHLBI) (NIH)

225

Enrollment

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The overall aims of this protocol are to determine whether prenatal supplementation with vitamin C to pregnant smokers can improve pulmonary function at 10 years of age in their offspring. This is an additional continuation of the Vitamin C to Decrease Effects of Smoking in Pregnancy on Infant Lung Function (VCSIP) trial, to follow the offspring through 10 years of age. The hypothesis for this protocol is an extension of the VCSIP trial that supplemental vitamin C in pregnant smokers can significantly improve their children's airway function tests. The investigators aim to demonstrate sustained improvement in airway/pulmonary function and trajectory through 10 years of age.

Condition or Disease	Intervention/Treatment	Phase
Asthma Pulmonary Function Wheezing In Utero Nicotine	Dietary Supplement: No active intervention in this protocol (previously randomized to Vitamin C) Other: No active intervention in this protocol (previously randomized to Placebo)

Detailed Description

The primary outcome of this longitudinal follow-up study is the comparison of airway function tests (specifically the forced expiratory flow between 25%and 75% of expired volume [FEF25-75]) measured yearly through 10 years of age by forced expiratory maneuvers with spirometry between the children of the pregnant smokers randomized to vitamin C (500 mg/day) versus placebo during pregnancy. The occurrence of wheeze obtained with quarterly standardized respiratory questionnaires will also be compared between the two groups of children. This is a follow-up of the original "Vitamin C to Decrease Effects of Smoking in Pregnancy on Infant Lung Function" (VCSIP) trial.

The secondary outcomes are:

A single low dose high-resolution computed tomography (HRCT) image of the lungs (acquired during inspiration) will be done at 10 years of age in offspring of pregnant smokers who were randomized to vitamin C (500 mg/day) versus placebo during pregnancy. Image analysis will be performed by Dr. Miranda Kirby's Quantitative Image Analysis in Medicine laboratory at Ryerson University in Toronto, ON using certified pulmonary image analysis software. The airway lumen cross sectional areas to at least the fifth generation of airways will be compared between the two groups of children. The number of airways and the lumen, wall, and total cross sectional areas and the segment lengths will also be quantified.
A secondary aim is to quantify the differences in DNA methylation between the two groups and measure the correlation between the differences in DNA methylation and respiratory outcomes.

Study Design

Study Type:

Observational

Anticipated Enrollment :

225 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Assessing the Effect of Vitamin C on Infant Lung Function When Given to Pregnant Women Who Smoke - (Long Term Follow-up of a Randomized Trial)

Anticipated Study Start Date :

Oct 1, 2023

Anticipated Primary Completion Date :

Aug 1, 2027

Anticipated Study Completion Date :

Aug 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Offspring of smokers who received Vitamin C In the original VCSIP study, pregnant women were randomized to receive either extra Vitamin C every day (500mg/day) or placebo.	Dietary Supplement: No active intervention in this protocol (previously randomized to Vitamin C) In the original VCSIP study, pregnant women were randomized to receive either extra Vitamin C every day (500mg/day) or placebo. This trial is a follow-up trial with no active intervention.
Offspring of smokers who received Placebo In the original VCSIP study, pregnant women were randomized to receive either extra Vitamin C every day (500mg/day) or placebo.	Other: No active intervention in this protocol (previously randomized to Placebo) In the original VCSIP study, pregnant women were randomized to receive either extra Vitamin C every day (500mg/day) or placebo. This trial is a follow-up trial with no active intervention.
Offspring of non-smokers

Arm

Intervention/Treatment

Offspring of smokers who received Vitamin C

In the original VCSIP study, pregnant women were randomized to receive either extra Vitamin C every day (500mg/day) or placebo.

Dietary Supplement: No active intervention in this protocol (previously randomized to Vitamin C)

In the original VCSIP study, pregnant women were randomized to receive either extra Vitamin C every day (500mg/day) or placebo. This trial is a follow-up trial with no active intervention.

Offspring of smokers who received Placebo

In the original VCSIP study, pregnant women were randomized to receive either extra Vitamin C every day (500mg/day) or placebo.

Other: No active intervention in this protocol (previously randomized to Placebo)

In the original VCSIP study, pregnant women were randomized to receive either extra Vitamin C every day (500mg/day) or placebo. This trial is a follow-up trial with no active intervention.

Offspring of non-smokers

Outcome Measures

Primary Outcome Measures

Sustained improvement in pulmonary function and trajectory [10 years of age]
The primary outcome of this longitudinal follow-up study is the comparison of airway function tests (specifically FEF25-75 in liters/sec) measured yearly through 10 years of age by forced expiratory maneuvers with spirometry between the children of the pregnant smokers randomized to vitamin C (500 mg/day) versus placebo during pregnancy. This is a follow-up of the original "Vitamin C to Decrease Effects of Smoking in Pregnancy on Infant Lung Function" (VCSIP) trial.

Secondary Outcome Measures

Occurrence of wheeze [10 years of age]
The occurrence of wheeze obtained with quarterly standardized respiratory questionnaires will also be compared between the children of the pregnant smokers randomized to vitamin C (500 mg/day) versus placebo during pregnancy. This is a follow-up of the original "Vitamin C to Decrease Effects of Smoking in Pregnancy on Infant Lung Function" (VCSIP) trial.
Airway lumen cross sectional areas [10 years of age]
A single low dose high-resolution computed tomography (HRCT) image of the lungs (acquired during inspiration) will be done at 10 years of age in offspring of pregnant smokers who were randomized to vitamin C (500 mg/day) versus placebo during pregnancy. Image analysis will be performed by Dr. Miranda Kirby's Quantitative Image Analysis in Medicine laboratory at Ryerson University in Toronto, ON using certified pulmonary image analysis software. The airway lumen cross sectional areas (in mm squared) to at least the fifth generation of airways will be compared between the two groups of children.
Changes in DNA methylation [10 years of age]
A secondary aim is to quantify the differences in DNA methylation between the two groups and measure the correlation between the differences in DNA methylation and respiratory outcomes.

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 16 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Women and their offspring randomized to vitamin C versus placebo during pregnancy as well as pregnant nonsmokers and their offspring enrolled as the reference group in the original VCSIP study