Clinical trial NCT01723696: Vitamin C to Decrease Effects of Smoking in Pregnancy on Infant Lung Function
Official title: Vitamin C to Decrease Effects of Smoking in Pregnancy on Infant Lung Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
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
Lead sponsor: Oregon Health and Science University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Office of Dietary Supplements (ODS)
First posted: 2012-11-08
Enrollment: 252
Sex: FEMALE
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

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.

Eligibility criteria: Inclusion Criteria: At randomization:

* Singleton gestation
* ≥ 15 years old
* Gestational age between 13 and 22 weeks
* Receiving prenatal care
* Current smoker
* English speaking

Exclusion Criteria:

* 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
* 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

Primary outcomes:
measure: Forced Expiratory Flow at 75% of Expired Volume (FEF75)
timeFrame: 3 months of age
Secondary outcomes:
measure: Forced Expiratory Flow at 75% of Expired Volume (FEF75)
timeFrame: 12 months of age
measure: Incidence of Wheezing Through 12 Months of Age
timeFrame: 12 months of age
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
Study officials:
affiliation: Oregon Health and Science University
name: Cynthia T McEvoy, MD,MCR
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.