Pulmonary Function; Newborn, AbnormalPhase 2/3VCSIPNCT01723696
Vitamin C to Decrease Effects of Smoking in Pregnancy on Infant Lung Function
A Phase 2/3 study testing Vitamin C +prenatal vitamin in people with Pulmonary Function; Newborn, Abnormal and Infant Wheeze, run by Oregon Health and Science University at 2 sites in United States.
Trial summary
Vitamin C supplementation (500 mg per day) given to pregnant women who can not quit smoking will improve the pulmonary function tests in their offspring measured at 3 months of age. Read more about this study
- Who is it for?
- Ages 15 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Pulmonary Function; Newborn, Abnormal, Infant Wheeze, In-utero Nicotine
- What is being tested?
- Vitamin C +prenatal vitamin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 252 participants
- Where
- 2 sitesUnited States
- Study dates
- Dec 2012to Dec 2017
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 15 years and older
- Women only
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Singleton gestation
- ≥ 15 years old
- Gestational age between 13 and 22 weeks
- Receiving prenatal care
- Current smoker
- English speaking
Who cannot join
- Gestational age ≥ 23 and 0/7 weeks
- Multiple gestation
- Major fetal congenital anomalies
- Current use of illicit drugs
- Current alcohol abuse
- Use of vitamin C (≥ 500 mg/day)>3 days per week since last menstrual period
Show all 17Show fewer
- Refusal to abstain from vitamin or supplements containing significant vitamin C other than those provided through or approved by study staff
- History of kidney stone in patient
- Insulin dependent diabetes
- Complex maternal medical conditions
- Participation in other conflicting research projects
- Unable to demonstrate stable method of communication
- Pregnancy by in-vitro fertilization
- Plan to terminate pregnancy
- Failure of medication compliance trial
- Failure to return in designated period during placebo run-in
- Body mass index > 50 at screening
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Indiana University
Indianapolis, Indiana, 46202-5167
Oregon Health & Science University
Portland, Oregon, 97239
About this study
Vitamin C supplementation (500 mg per day) given to pregnant women who can not quit smoking will improve the pulmonary function tests in their offspring measured at 3 months of age.
Read the detailed description
Smoking during pregnancy remains a major public health problem as at least 12% of pregnant women cannot quit smoking during pregnancy. This addiction is the largest preventable cause of childhood respiratory illness, including asthma, and children whose mothers smoked during pregnancy show lifetime decreases in pulmonary function. Smoking is a unique morbidity in that it is addictive, heavily advertised and recent genome studies show there are genotypes that significantly increase the likelihood of being unable to quit. Teen pregnancy, low income, low education, and living with another smoker are important factors increasing the odds of smoking during pregnancy. Pulmonary function tests done shortly after birth in babies born to mothers who smoked during pregnancy show decreased pulmonary function as measured by decreased respiratory flows and respiratory compliance and altered tidal breathing patterns. These changes can still be measured even after the infants have reached adulthood. Multiple epidemiologic studies show that these decreases in pulmonary function lead to increased respiratory disease and costs of hundreds of millions of dollars per year.
The primary aim of this double-blind, placebo controlled, randomized, multi-site study is to demonstrate improved pulmonary function testing at 3 months of age, in infants delivered to smoking mothers who are randomized to 500 mg/day of supplemental vitamin C versus placebo at less than or equal to 22 weeks of pregnancy. We will recruit 278 smoking pregnant women into the study. Patients will meet with research personnel at each prenatal visit and smoking cessation will be actively encouraged. Patients will be monitored with a set of serial biomarkers to assess smoking and medication compliance, including urine cotinine levels, smoking questionnaires, pill counts and fasting plasma ascorbic acid levels. Pulmonary function tests will be done at 3 months of age and will measure forced expiratory flows. The infants will also be followed through one year of age with monthly validated respiratory questionnaires and a follow-up pulmonary function test at 12 months of age. Success of this study is supported by strong pilot data showing statistically significant improvements at about 48 hours of age in pulmonary function tests in infants born to smoking mothers who received vitamin C versus placebo, and preliminary data showing a lower incidence of wheezing at 12 months of age in these infants. Key genetic polymorphisms shown to increase sensitivity to in-utero smoke exposure will also be measured. The success of this study is also supported by animal models showing the effectiveness of vitamin C to preserve pulmonary function and genetic and epidemiologic studies linking the effects of smoking during pregnancy to oxidant mechanisms. The secondary aims of the study include: 1) to demonstrate a decreased incidence of wheezing through 12 months of age in infants delivered to smoking mothers who are randomized to 500mg/day of supplemental vitamin C versus placebo during pregnancy; 2) to demonstrate improved pulmonary function tests at 12 months of age in these infants.
- Conditions
- Pulmonary Function; Newborn, Abnormal, Infant Wheeze, In-utero Nicotine, Second Hand Smoke
- Being tested
- Vitamin C +prenatal vitamin, Placebo tablet+prenatal vitamin
- Keywords
- In-utero smoke;, Pulmonary function testing;, Wheeze;, Vitamin C;, Forced expiratory flows
- Medical subject headings
- Antisocial Personality Disorder, Respiratory Sounds
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin C +prenatal vitaminDietary supplement
Also called Ascorbic acid
Pregnant smoking women will be randomized to daily vitamin C (500 mg) versus daily placebo
Placebo tablet+prenatal vitaminDietary supplement
| Study group | Role | What they receive |
|---|---|---|
| placebo tablet+prenatal vitamin | Placebo comparator | A daily placebo tablet Receives: Dietary Supplement: Placebo tablet+prenatal vitamin |
| Vitamin C +prenatal vitamin | Active comparator | 500 mg vitamin C /day Receives: Dietary Supplement: Vitamin C +prenatal vitamin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Forced Expiratory Flow at 75% of Expired Volume (FEF75)
The primary outcome was the comparison of infant FEFs at 3 months of age obtained using the raised volume rapid thoracic compression (RVRTC) technique in offspring of pregnant smokers randomized to vitamin C versus placebo. The specific primary outcome parameter was the measurement of FEF at 75% of the expired volume (FEF75)
Measured: 3 months of age
Secondary outcomes (2)
Forced Expiratory Flow at 75% of Expired Volume (FEF75)
The measurement of forced expiratory flows and specifically FEF75 will be done at 12 months of age in infants born to pregnant smoking women randomized to vitamin C versus placebo during pregnancy. FEF75 will be measured with the raised volume rapid thoracic compression technique.
Measured: 12 months of age
Incidence of Wheezing Through 12 Months of Age
The incidence of wheezing through 12 months of age will be compared in the infants delivered to smoking pregnant women who were randomized to vitamin C (500 mg) versus placebo during pregnancy.
Measured: 12 months of age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2012 (estimated)
- Study startDec 2012
- Primary completionApr 2016
- Study completionDec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Function; Newborn, AbnormalStudies 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
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 252 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oregon Health and Science University
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Office of Dietary Supplements (ODS)
- Responsible party
- Principal investigator, Cynthia McEvoy, Oregon Health and Science University
- Investigators
- Cynthia T McEvoy, MD,MCR, Principal investigator, Oregon Health and Science University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01723696
- Sponsor's protocol ID
- HL105447
- Other IDs
- R01HL105447
- Acronym
- VCSIP
- Status last verified
- Mar 2019
- First submitted
- 6 Nov 2012
- Last updated
- 17 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Shorey-Kendrick LE, McEvoy CT, Milner K, Harris J, Brownsberger J, Tepper RS, Park B, Gao L, Vu A, Morris CD, Thompson EE, Ober C, Spindel ER. Vitamin C supplementation to pregnant smokers alters asthma- and allergy-associated CpGs in child buccal DNA at 5 years of age. Clin Epigenetics. 2025 Oct 3;17(1):155. doi: 10.1186/s13148-025-01965-2.
PubMed 41044653Shorey-Kendrick LE, McEvoy CT, Milner K, Harris J, Brownsberger J, Tepper RS, Park B, Gao L, Vu A, Morris CD, Spindel ER. Improvements in lung function following vitamin C supplementation to pregnant smokers are associated with buccal DNA methylation at 5 years of age. Clin Epigenetics. 2024 Feb 27;16(1):35. doi: 10.1186/s13148-024-01644-8.
PubMed 38413986Shorey-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 34538263McEvoy 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 30522343
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vitamin C to Decrease Effects of Smoking in Pregnancy on Infant Lung Function
- ClinicalTrials.gov ID
- NCT01723696
- Acronym / sponsor ID
- VCSIP / HL105447
- Conditions
- Pulmonary Function; Newborn, Abnormal, Infant Wheeze, In-utero Nicotine, Second Hand Smoke
- Keywords
- In-utero smoke;, Pulmonary function testing;, Wheeze;, Vitamin C;, Forced expiratory flows
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 252 participants (actual)
- Lead sponsor
- Oregon Health and Science UniversityUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Office of Dietary Supplements (ODS)
- Study start
- Dec 2012
- Primary completion
- Apr 2016 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 8 Nov 2012 (estimated)
- Results
- Posted 17 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Vitamin C supplementation (500 mg per day) given to pregnant women who can not quit smoking will improve the pulmonary function tests in their offspring measured at 3 months of age.
Detailed description
Smoking during pregnancy remains a major public health problem as at least 12% of pregnant women cannot quit smoking during pregnancy. This addiction is the largest preventable cause of childhood respiratory illness, including asthma, and children whose mothers smoked during pregnancy show lifetime decreases in pulmonary function. Smoking is a unique morbidity in that it is addictive, heavily advertised and recent genome studies show there are genotypes that significantly increase the likelihood of being unable to quit. Teen pregnancy, low income, low education, and living with another smoker are important factors increasing the odds of smoking during pregnancy. Pulmonary function tests done shortly after birth in babies born to mothers who smoked during pregnancy show decreased pulmonary function as measured by decreased respiratory flows and respiratory compliance and altered tidal breathing patterns. These changes can still be measured even after the infants have reached adulthood. Multiple epidemiologic studies show that these decreases in pulmonary function lead to increased respiratory disease and costs of hundreds of millions of dollars per year.
The primary aim of this double-blind, placebo controlled, randomized, multi-site study is to demonstrate improved pulmonary function testing at 3 months of age, in infants delivered to smoking mothers who are randomized to 500 mg/day of supplemental vitamin C versus placebo at less than or equal to 22 weeks of pregnancy. We will recruit 278 smoking pregnant women into the study. Patients will meet with research personnel at each prenatal visit and smoking cessation will be actively encouraged. Patients will be monitored with a set of serial biomarkers to assess smoking and medication compliance, including urine cotinine levels, smoking questionnaires, pill counts and fasting plasma ascorbic acid levels. Pulmonary function tests will be done at 3 months of age and will measure forced expiratory flows. The infants will also be followed through one year of age with monthly validated respiratory questionnaires and a follow-up pulmonary function test at 12 months of age. Success of this study is supported by strong pilot data showing statistically significant improvements at about 48 hours of age in pulmonary function tests in infants born to smoking mothers who received vitamin C versus placebo, and preliminary data showing a lower incidence of wheezing at 12 months of age in these infants. Key genetic polymorphisms shown to increase sensitivity to in-utero smoke exposure will also be measured. The success of this study is also supported by animal models showing the effectiveness of vitamin C to preserve pulmonary function and genetic and epidemiologic studies linking the effects of smoking during pregnancy to oxidant mechanisms. The secondary aims of the study include: 1) to demonstrate a decreased incidence of wheezing through 12 months of age in infants delivered to smoking mothers who are randomized to 500mg/day of supplemental vitamin C versus placebo during pregnancy; 2) to demonstrate improved pulmonary function tests at 12 months of age in these infants.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| placebo tablet+prenatal vitamin | Placebo comparator | Dietary Supplement: Placebo tablet+prenatal vitaminA daily placebo tablet |
| Vitamin C +prenatal vitamin | Active comparator | Dietary Supplement: Vitamin C +prenatal vitamin500 mg vitamin C /day |
Who may qualify
- Ages
- 15 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Singleton gestation
- ≥ 15 years old
- Gestational age between 13 and 22 weeks
- Receiving prenatal care
- Current smoker
Key exclusion criteria (17 listed)
- Gestational age ≥ 23 and 0/7 weeks
- Multiple gestation
- Major fetal congenital anomalies
- Current use of illicit drugs
- Current alcohol abuse
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 |
|---|---|---|
| Vitamin C +prenatal vitaminAlso: Ascorbic acidPregnant smoking women will be randomized to daily vitamin C (500 mg) versus daily placebo | Dietary supplement | Vitamin C +prenatal vitamin |
| Placebo tablet+prenatal vitamin | Dietary supplement | placebo tablet+prenatal vitamin |
Primary outcome
Forced Expiratory Flow at 75% of Expired Volume (FEF75)
Time frame: 3 months of age
The primary outcome was the comparison of infant FEFs at 3 months of age obtained using the raised volume rapid thoracic compression (RVRTC) technique in offspring of pregnant smokers randomized to vitamin C versus placebo. The specific primary outcome parameter was the measurement of FEF at 75% of the expired volume (FEF75)
2 secondary outcomes
Forced Expiratory Flow at 75% of Expired Volume (FEF75)
Time frame: 12 months of age
Incidence of Wheezing Through 12 Months of Age
Time frame: 12 months of age
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41044653Shorey-Kendrick LE, McEvoy CT, Milner K, Harris J, Brownsberger J, Tepper RS, Park B, Gao L, Vu A, Morris CD, Thompson EE, Ober C, Spindel ER. Vitamin C supplementation to pregnant smokers alters asthma- and allergy-associated CpGs in child buccal DNA at 5 years of age. Clin Epigenetics. 2025 Oct 3;17(1):155. doi: 10.1186/s13148-025-01965-2.
- Derived from this study: PubMed 38413986Shorey-Kendrick LE, McEvoy CT, Milner K, Harris J, Brownsberger J, Tepper RS, Park B, Gao L, Vu A, Morris CD, Spindel ER. Improvements in lung function following vitamin C supplementation to pregnant smokers are associated with buccal DNA methylation at 5 years of age. Clin Epigenetics. 2024 Feb 27;16(1):35. doi: 10.1186/s13148-024-01644-8.
- Derived from this study: 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.
- Derived from this study: 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.
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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. This study is not recruiting at the moment.
Cynthia T 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?
A Phase 2/3 study testing Vitamin C +prenatal vitamin in people with Pulmonary Function; Newborn, Abnormal and Infant Wheeze, 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 6 inclusion and 17 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: finished, as of the sponsor's last update on 17 Apr 2019. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Forced Expiratory Flow at 75% of Expired Volume (FEF75) (time frame: 3 months 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 NCT01723696, which also lists 4 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 17 Apr 2019.