Bupropion for Smoking Cessation During Pregnancy

Study Overview
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Brief Summary
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This is a prospective, double-blind placebo-controlled randomized pilot trial of the preliminary safety and efficacy of bupropion SR in combination with behavioral counseling for smoking cessation during pregnancy.

Detailed Description
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This is a prospective, double-blind placebo-controlled randomized pilot trial of the preliminary safety and efficacy of bupropion SR in combination with behavioral counseling for smoking cessation during pregnancy. A total of 150 pregnant smokers will receive medication (75) or placebo (75) for 12 weeks. Compassionate care/continuance of therapy will be available to pregnant subjects. Women who relapse to smoking postpartum will be offered an additional course of medication treatment. All subjects regardless of adherence with 12 week study drug administration period and smoking habits during pregnancy will be followed through the duration of their pregnancy, delivery, and 6-month postpartum period. Subject participation will begin between 13-30 wks of gestation and end 6 months postpartum. Participation will be ten (10) to thirteen(13) months in length.

Official Title
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Bupropion for Smoking Cessation During Pregnancy

Conditions
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Pregnancy Related, Tobacco Use Disorder

Intervention / Treatment
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* Drug: Bupropion SR
* Behavioral: Smoking Cessation Counseling
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: smoking at least 10 CPD prior to pregnancy and 5 CPD for the preceding 7 days 13-30 weeks gestation ≥18 years of age able to speak English or Spanish intent to carry pregnancy to term stable residence Exclusion Criteria: current illicit drug or alcohol abuse or dependence twins or other multiple gestation treatment for psychiatric disorder within the last 6 months unstable medical problems (eg, hypertension (BP>140/90), preeclampsia, threatened abortion, hyperemesis gravidarum) known congenital abnormality seizure disorder use of psychotropic medication use of medication known to lower the seizure threshold anorexia/bulimia a personal history of closed head trauma with > 30 minutes of loss of consciousness or amnesia or resulting in skull fracture or subdural hematoma/brain contusion use of any other smoking cessation treatment in the past 30 days current enrollment in methadone treatment program prior pregnancy with preeclampsia diagnosis chronic hypertension (past history or current diagnosis)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Bupropion SR + cessation counseling<br>Bupropion SR and smoking cessation counseling Subjects received Bupropion SR 150 mg tablet orally twice daily (BID) for 12 weeks. Subjects were instructed to begin using study medication (bupropion SR 150 mg orally for 3 days, then BID for 4 days) on study visit day 1, which was approximately 1 week prior to their quit date. Thereafter, they were continued to dose Bupropion SR 150 mg tablet orally BID for a total medication treatment of 12 full weeks. Smoking cessation counseling included 35-minute counseling sessions at each of the first 2 visits and 10 minutes of smoking cessation counseling at subsequent visits, provided by the trained study nurse. | Drug: Bupropion SR<br>* Bupropion SR 150 mg tablet<br>* Other names: buproban;Behavioral: Smoking Cessation Counseling<br>* 35-min counseling by trained research nurse<br>* Other names: Behavioral counseling;|
| Placebo Comparator: Placebo + cessation counseling<br>Placebo and smoking cessation counseling Subjects received matching Bupropion SR placebo tablet orally twice daily (BID) for 12 weeks. Subjects were instructed to begin using study medication (matched placebo tablets orally for 3 days, then BID for 4 days) on study visit day 1, which was approximately 1 week prior to their quit date. Thereafter, they were continued to dose matching Bupropion SR placebo tablet orally BID for a total medication treatment of 12 full weeks of therapy. Smoking cessation counseling included 35-minute counseling sessions at each of the first 2 visits and 10 minutes of smoking cessation counseling at subsequent visits, provided by the trained study nurse. | Behavioral: Smoking Cessation Counseling<br>* 35-min counseling by trained research nurse<br>* Other names: Behavioral counseling;Drug: Placebo<br>* Matching Bupropion SR placebo tablet<br>* Other names: Control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Cigarette Craving and Total Nicotine Withdrawal Symptoms Between Groups During Medication Treatment | Cigarette craving and withdrawal symptoms were assessed by the Minnesota Nicotine Withdrawal Scale (MNWS). MNWS consists of 7 objectives (e.g., irritability, anxious, depressed mood, difficulty concentrating, increased appetite, insomnia, restless). Subjects were given a score on each item on a scale of 0 (not present) to 4 (severe). Summed (total) score excluding craving represent subject's symptoms of tobacco withdrawal, ranging from 0 to 28. We calculated a craving for tobacco score and a total score of withdrawal symptoms excluding craving. The higher score represent more sever craving and withdrawal. | During treatment: Visits 2-6 (time period between 2nd and 12th week of therapy) | 
| Change in Cigarette Craving and Total Nicotine Withdrawal Symptoms Between Groups on the Quit Date | Cigarette craving and withdrawal symptoms were assessed by the Minnesota Nicotine Withdrawal Scale (MNWS). MNWS consists of 7 objectives (e.g., irritability, anxious, depressed mood, difficulty concentrating, increased appetite, insomnia, restless). Subjects were given a score on each item on a scale of 0 (not present) to 4 (severe). Summed (total) score excluding craving represent subject's symptoms of tobacco withdrawal, ranging from 0 to 28. We calculated a craving for tobacco score and a total score of withdrawal symptoms excluding craving. The higher score represent more sever craving and withdrawal. | Quit date, visit 2 (one week after starting the 12-week course of therapy) | 
| Number of Participants With 7-day Point Prevalence Smoking Abstinence at the End of Medication Treatment (Visit 6) | The accuracy of self-reported smoking abstinence during study visits was confirmed by an exhaled carbon monoxide (CO) levels and by urinary cotinine levels. 7-day point prevalence abstinence was defined as no cigarettes (not even a puff) in the last 7 days, levels of (CO) in exhaled air < 4 ppm, and concentrations of cotinine in urine < 50 ng/mL. At every visit, a research nurse monitored the smoking status of all subjects (amount of cigarettes per day, exhaled CO). Exhaled CO was measured using a Vitalograph carbon monoxide monitor (Lenexa, KS) according to the manufacturer's recommendations. A urine sample was collected at each visit and cotinine in urine was quantified using the validated liquid chromatography-mass spectrometry (LC/MS) method. We calculated the total number of abstinent subjects. The higher the number the better outcome. | Visit 6 (end of 12 weeks of medication therapy) | 
| Number of Participants With 7-day Point Prevalence Smoking Abstinence at the End of Pregnancy (Visit 7) | The accuracy of self-reported smoking abstinence during study visits was confirmed by an exhaled carbon monoxide (CO) levels and by urinary cotinine levels. 7-day point prevalence abstinence was defined as no cigarettes (not even a puff) in the last 7 days, levels of (CO) in exhaled air < 4 ppm, and concentrations of cotinine in urine < 50 ng/mL. At every visit, a research nurse monitored the smoking status of all subjects (amount of cigarettes per day, exhaled CO). Exhaled CO was measured using a Vitalograph carbon monoxide monitor (Lenexa, KS) according to the manufacturer's recommendations. A urine sample was collected at each visit and cotinine in urine was quantified using the validated liquid chromatography-mass spectrometry (LC/MS) method. We calculated the total number of abstinent subjects. The higher the number the better outcome. | End of pregnancy (visit 7) is a time period between 36.0-38.6 weeks gestation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pregnancy, Tobacco use disorder, Smoking cessation, Bupropion SR, Zyban