AsthmaVCSIPNCT06106646
Vitamin C to Decrease Effects of Smoking in Pregnancy on Infant Lung Function (VCSIP) Longer Term Follow Up
An observational study of Asthma and Pulmonary Function, run by Oregon Health and Science University at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 16 years
- Conditions the study is for
- Asthma, Pulmonary Function, Wheezing
- What is being tested?
- No active intervention in this protocol (previously randomized to Vitamin C)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 225 participants
- Where
- 2 sitesUnited States
- Study dates
- 11 Oct 2023to Aug 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 16 years
- All sexes
- No healthy volunteers
- Child
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).
Who may be able to join
- 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
Who cannot join
- participants who specifically withdraw consent
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Indiana University
Indianapolis, Indiana, 46902
Christina Tiller, ctiller@iu.edu
Robert Tepper, MD
- Recruiting
Oregon Health and Science University (OHSU)
Portland, Oregon, 97217
Kristin Milner, 971-404-0223, milner@ohsu.edu
Cindy McEvoy, MD
About this study
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)
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.
Read the 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.
- Conditions
- Asthma, Pulmonary Function, Wheezing, In Utero Nicotine
- Being tested
- No active intervention in this protocol (previously randomized to Vitamin C), No active intervention in this protocol (previously randomized to Placebo)
- Keywords
- Asthma, Pulmonary Function, Pulmonary Function Testing, Wheeze, Vitamin C, Antioxidants, Forced Expiratory Flows, Spirometry, Lung Function, Epigenetics, High resolution CT scans
- Medical subject headings
- Asthma, Respiratory Sounds
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No active intervention in this protocol (previously randomized to Vitamin C)Dietary supplement
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.
No active intervention in this protocol (previously randomized to Placebo)Other
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Dietary Supplement: No active intervention in this protocol (previously randomized to Vitamin C) | |
| 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. Receives: Other: No active intervention in this protocol (previously randomized to Placebo) | |
| Offspring of non-smokers | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sustained improvement in pulmonary function and trajectory
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.
Measured: 10 years of age
Secondary outcomes (3)
Occurrence of wheeze
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.
Measured: 10 years of age
Airway lumen cross sectional areas
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.
Measured: 10 years of age
Changes in DNA methylation
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.
Measured: 10 years of age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2023
- Study start11 Oct 2023
- Primary completionAug 2027 (estimated)
- Study completionAug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 225 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Oregon Health and Science University
- Sponsor type
- University, hospital or other
- Collaborators
- Indiana University, National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Cynthia McEvoy, Oregon Health and Science University
- Investigators
- Cindy McEvoy, MD, MCR, Principal investigator, Oregon Health and Science University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06106646
- Sponsor's protocol ID
- VCSIP LTFU
- Other IDs
- R01HL162951
- Acronym
- VCSIP
- Status last verified
- Mar 2025
- First submitted
- 9 Oct 2023
- Last updated
- 18 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 24838476McEvoy 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.
PubMed 36409489McEvoy 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.
PubMed 32616589Blue 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.
PubMed 37580504McEvoy 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.
PubMed 30522343Shorey-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.
PubMed 34538263
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT06106646
- Acronym / sponsor ID
- VCSIP / VCSIP LTFU
- Conditions
- Asthma, Pulmonary Function, Wheezing, In Utero Nicotine
- Keywords
- Asthma, Pulmonary Function, Pulmonary Function Testing, Wheeze, Vitamin C, Antioxidants, Forced Expiratory Flows, Spirometry
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 225 participants (estimated)
- Lead sponsor
- Oregon Health and Science UniversityUniversity, hospital or other
- Collaborators
- Indiana University, National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 11 Oct 2023 (actual)
- Primary completion
- Aug 2027 (estimated)
- Study completion
- Aug 2028 (estimated)
- First posted
- 30 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Offspring of smokers who received Vitamin C | – | 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. |
| Offspring of smokers who received 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. |
| Offspring of non-smokers | – | – |
Who may qualify
- Ages
- 6 to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- 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).
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (1 listed)
- participants who specifically withdraw consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Dietary supplement | Offspring of smokers who received Vitamin C |
| 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. | Other | Offspring of smokers who received Placebo |
Primary outcome
Sustained improvement in pulmonary function and trajectory
Time frame: 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.
3 secondary outcomes
Occurrence of wheeze
Time frame: 10 years of age
Airway lumen cross sectional areas
Time frame: 10 years of age
Changes in DNA methylation
Time frame: 10 years of age
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2025.
- Background: PubMed 24838476McEvoy 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.
- Background: PubMed 36409489McEvoy 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.
- Background: PubMed 32616589McEvoy 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.
- Background: PubMed 37580504Blue 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.
- Background: PubMed 30522343McEvoy 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.
- Background: PubMed 34538263Shorey-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.
- Individual participant dataSharing planned: Undecided
Related trials for Asthma
Enrolling by invitationObservational study
Allergy, Asthma, and Atopic Eczema in Finland
Asthma, Asthma in Children
RecruitingPhase 2
Rademikibart IV for Acute Asthma and COPD Exacerbation
Asthma Acute, COPD Exacerbation Acute
Active, not recruiting
Community Health Equity Accelerator (CHEA) Pediatric Asthma Intervention
Asthma in Children
Enrolling by invitationObservational study
Firefighter's Longitudinal Airway and Respiratory Exposome/Multiome Study (FLARES)
Anosmia, Chronic Obstructive Pulmonary Disease
RecruitingObservational study
NHALES (Natural History of Asthma With Longitudinal Environmental Sampling)
Asthma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Cindy McEvoy, MD, MCR principal investigator
Oregon Health and Science University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Asthma and Pulmonary Function, run by Oregon Health and Science University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Cindy McEvoy, MD, MCR (503-494-0223, mcevoyc@ohsu.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sustained improvement in pulmonary function and trajectory (time frame: 10 years of age). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06106646, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2025.