Smoking during pregnancy is an important modifiable cause of poor pregnancy outcomes. Even with augmented behavioral interventions, smoking cessation rates in pregnancy trials rarely exceed 20%. These low quit rates may be due to inadequate treatment of the physical dependence on nicotine. Indeed, medications, which may help to reduce nicotine withdrawal symptoms, are a first-line treatment for smoking treatment in non-pregnant smokers. However, little information is available on the safety or efficacy of medications to treat pregnant smokers.

The purpose of this trial is to evaluate the safety and effectiveness of 2 mg nicotine gum in promoting smoking cessation during pregnancy. The design is a randomized, placebo controlled trial where subjects are randomized to nicotine gum (6 weeks ad libitum use followed by a 6 week taper) or a matching placebo. Women who are doing well at the end of the trial will also be offered gum post-partum for relapse prevention.

Condition	Treatment or Intervention	Phase
Nicotine Dependence Pregnancy	Drug: Nicotine Replacement (2 mg Gum)  Behavior: Augmented Motivational Behavioral Therapy	Phase II

Further Study Details: 

Expected Total Enrollment:  268

Smoking during pregnancy is an important modifiable cause of poor pregnancy outcomes. Even with augmented behavioral interventions, smoking cessation rates in pregnancy trials rarely exceed 20%. These low quit rates may be due to inadequate treatment of the physical dependence on nicotine. Indeed, medications, which may help to reduce nicotine withdrawal symptoms, are a first-line treatment for smoking treatment in non-pregnant smokers. However, little information is available on the safety or efficacy of medications to treat pregnant smokers. This proposal will examine the utility of one first-line medication, nicotine gum, as an aid to smoking cessation during pregnancy. The specific aims are: (1) To compare smoking cessation rates and smoking reduction among pregnant smokers who are randomized to receive nicotine gum (starting at 2 mg dose that may be increased to 4 mg) or a matching placebo; (2) To compare nicotine gum versus placebo on surrogate measures of maternal and fetal safety (i.e., overall nicotine and tobacco exposure at 6 weeks after the quit date and at 32-34 weeks gestation), and birth weight at the time of delivery; (3) To examine which subjects benefit the most from the use of nicotine gum for smoking cessation during pregnancy; and (4) To examine the interaction between maternal smoking, maternal genotype [a selected phase I gene of drug metabolism -cytochrome P450 1A1 (CYP1A1) and a phase II gene of drug metabolism [(glutathione S-transferase theta-GSTTI)] on birth weight. As an exploratory aim we will also evaluate the interaction between smoking cessation and other selected phase I and II genes of drug metabolism on birth weight. Subjects will be recruited from a prenatal clinic that serves primarily a low-income, minority population. Two hundred sixty-eight pregnant smokers will be randomly assigned to receive smoking cessation behavioral counseling and either a 6-week course of placebo or nicotine gum, followed by a 6-weeks of decreasing doses. Maternal blood for genotyping will be obtained at study entry. Primary outcome measures will be 7-day point prevalence of cigarette abstinence, number of cigarettes smoked per day, saliva cotinine concentrations, and measures of tobacco exposure (i.e., carbon monoxide in exhaled air, and urine anabasine and anatabine) at 6 weeks after the quit date and at 32-34 weeks gestation, and infant birth weight. For Specific Aim 4, two additional samples will be recruited, including 300 pregnant smokers from a similar study at Duke University (N=300) and 200 never smokers. We hypothesize that (1) Pregnant smokers who are randomized to nicotine gum will have double the quit rates, and will reduce their smoking to a greater degree than subjects randomized to placebo; (2) Nicotine gum compared to placebo will reduce maternal levels of tobacco-exposure markers and increase birth weights in the offspring; (3) The odds of cigarette abstinence will be increased primarily in subjects who smoke at least 15 cigarettes per day; and (4) Among pregnant smokers who continue to smoke throughout pregnancy, those who have alleles associated with increased CYP1A1 activity or with reduced GSTT1 activity will have lower birth weight infants compared to pregnant smokers with wild type variants at these alleles. In contrast, no association between genotype and birth weight will be observed in those pregnant smokers who quit by 28 weeks gestation and in never smokers. Results will be important for implementing future intervention programs designed to reduce rates and amount of maternal smoking and to improve outcomes of such high-risk pregnancies.

Ages Eligible for Study:  16 Years   -   50 Years,  Genders Eligible for Study:  Female

Criteria

Inclusion

• Patient's gestational age is 26 weeks or less.
• Patient is at least 16 years of age.
• Patient is able to speak English or Spanish.
• Patient intends to carry to term.
• Patient has stable residence.
• Patient has smoked five or more cigarettes everyday for the past seven days.

Exclusion

• Evidence that the patient is pregnant with a fetus with a known congenital abnormality.
• Unstable medical problems (i.e., hyperthyroidism, temporomandibular joint disorder, pre-eclampsia, threatened abortion, hyperemesis gravidarum)
• Multiple Gestation
• Unstable psychiatric disorder
• Current drug or alcohol abuse or dependence

Connecticut
      Hartford Hospital, Hartford,  Connecticut,  06102,  United States; Recruiting
      UCONN Health Center, Farmington,  Connecticut,  06030,  United States; Recruiting

Study ID Numbers:  RO1 DA 15167; UCHC IRB #02-146
Record last reviewed:  July 2003
Last Updated:  October 13, 2004
Record first received:  July 15, 2003
ClinicalTrials.gov Identifier:  NCT00064948
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08