Clinical trial NCT06106646: Vitamin C to Decrease Effects of Smoking in Pregnancy on Infant Lung Function (VCSIP) Longer Term Follow Up
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)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Asthma
Pulmonary Function
Wheezing
In Utero Nicotine
Keywords: Asthma
Pulmonary Function
Pulmonary Function Testing
Wheeze
Vitamin C
Antioxidants
Forced Expiratory Flows
Spirometry
Lung Function
Epigenetics
High resolution CT scans
Lead sponsor: Oregon Health and Science University
Sponsor class: OTHER
Collaborators: name: Indiana University
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2023-10-30
Enrollment: 225
Sex: ALL
Minimum age (years): 6
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: This is a follow up of NCT01723696. In that study, pregnant smokers were recruited at obstetric clinics delivering at OHSU in Portland OR, PeaceHealth Southwest Washington Medical Center in Vancouver, Washington or Indiana University in Indianapolis, Indiana. We are continuing to follow the offspring of those pregnant smokers (and control group non-smokers).

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.

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:

1. 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.
2. 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: 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

Exclusion Criteria:

* participants who specifically withdraw consent

Primary outcomes:
measure: Sustained improvement in pulmonary function and trajectory
timeFrame: 10 years of age
Secondary outcomes:
measure: Occurrence of wheeze
timeFrame: 10 years of age
measure: Airway lumen cross sectional areas
timeFrame: 10 years of age
measure: Changes in DNA methylation
timeFrame: 10 years of age
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Portland
country: United States
facility: Oregon Health and Science University (OHSU)
state: Oregon
Study officials:
affiliation: Oregon Health and Science University
name: Cindy McEvoy, MD, MCR
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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 their newborn infants: a randomized clinical trial. JAMA. 2014 May;311(20):2074-82. doi: 10.1001/jama.2014.5217.
citation: McEvoy CT, Shorey-Kendrick LE, Milner K, Harris J, Vuylsteke B, Cunningham M, Tiller C, Stewart J, Schilling D, Brownsberger J, Titus H, MacDonald KD, Gonzales D, Vu A, Park BS, Spindel ER, Morris CD, Tepper RS. Effect of Vitamin C Supplementation for Pregnant Smokers on Offspring Airway Function and Wheeze at Age 5 Years: Follow-up of a Randomized Clinical Trial. JAMA Pediatr. 2023 Jan 1;177(1):16-24. doi: 10.1001/jamapediatrics.2022.4401.
citation: McEvoy CT, Shorey-Kendrick LE, Milner K, Schilling D, Tiller C, Vuylsteke B, Scherman A, Jackson K, Haas DM, Harris J, Park BS, Vu A, Kraemer DF, Gonzales D, Bunten C, Spindel ER, Morris CD, Tepper RS. Vitamin C to pregnant smokers persistently improves infant airway function to 12 months of age: a randomised trial. Eur Respir J. 2020 Dec 3;56(6):1902208. doi: 10.1183/13993003.02208-2019. Print 2020 Dec.
citation: Blue SW, McEvoy CT, Spindel ER, Shorey-Kendrick LE, Davies MH, O'Sullivan SM, Erikson DW. Analysis of nicotine in plasma, brain, and hair samples with the same liquid chromatography-tandem mass spectrometry method. Rapid Commun Mass Spectrom. 2023 Sep 15;37(17):e9613. doi: 10.1002/rcm.9613. No abstract available.
citation: McEvoy CT, Shorey-Kendrick LE, Milner K, Schilling D, Tiller C, Vuylsteke B, Scherman A, Jackson K, Haas DM, Harris J, Schuff R, Park BS, Vu A, Kraemer DF, Mitchell J, Metz J, Gonzales D, Bunten C, Spindel ER, Tepper RS, Morris CD. Oral Vitamin C (500 mg/d) to Pregnant Smokers Improves Infant Airway Function at 3 Months (VCSIP). A Randomized Trial. Am J Respir Crit Care Med. 2019 May 1;199(9):1139-1147. doi: 10.1164/rccm.201805-1011OC.
citation: Shorey-Kendrick LE, McEvoy CT, O'Sullivan SM, Milner K, Vuylsteke B, Tepper RS, Haas DM, Park B, Gao L, Vu A, Morris CD, Spindel ER. Impact of vitamin C supplementation on placental DNA methylation changes related to maternal smoking: association with gene expression and respiratory outcomes. Clin Epigenetics. 2021 Sep 19;13(1):177. doi: 10.1186/s13148-021-01161-y.