Pregnancy Related, Tobacco Use Disorder
Conditions
Keywords
Pregnancy, Tobacco use disorder, Smoking cessation, Bupropion SR, Zyban
Brief summary
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
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.
Interventions
DRUGBupropion SR
Bupropion SR 150 mg tablet
BEHAVIORALSmoking Cessation Counseling
35-min counseling by trained research nurse
DRUGPlacebo
Matching Bupropion SR placebo tablet
Sponsors
National Institute on Drug Abuse (NIDA)
UConn Health
The University of Texas Medical Branch, Galveston
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Cigarette Craving and Total Nicotine Withdrawal Symptoms Between Groups During Medication Treatment | During treatment: Visits 2-6 (time period between 2nd and 12th week of therapy) | 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. |
| Change in Cigarette Craving and Total Nicotine Withdrawal Symptoms Between Groups on the Quit Date | Quit date, visit 2 (one week after starting the 12-week course of therapy) | 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. |
| Number of Participants With 7-day Point Prevalence Smoking Abstinence at the End of Medication Treatment (Visit 6) | Visit 6 (end of 12 weeks of medication therapy) | 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. |
| Number of Participants With 7-day Point Prevalence Smoking Abstinence at the End of Pregnancy (Visit 7) | End of pregnancy (visit 7) is a time period between 36.0-38.6 weeks gestation | 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. |
Countries
United States
Participant flow
Recruitment details
Pregnant smokers were recruited through the UTMB Ob/Gyn Department clinics and Regional Maternal Child Health Program (RMCHP) clinics. The study was also advertised through printed flyers, posters, and electronic media in clinic waiting areas. UTMB OB providers were notified of the study as well to refer potential participants.
Pre-assignment details
Psychological screening using the PRIME MD survey was administered after enrollment at the first Study Visit. Using the score, subjects with evidence of major depression or any other severe, acute psychiatric symptom (eg, psychosis) were considered screen failures and referred back to their prenatal provider for treatment.
Participants by arm
| Arm | Count |
|---|---|
| Bupropion SR Subjects received 150 mg tablet bupropion SR orally once daily for three days followed by twice daily for a total medication treatment of 12 weeks.
Subjects also received behavioral interventions, which included 35-minute counseling sessions at each of the first 2 visits (enrollment and on the quit day) and 10 minutes of smoking cessation counseling at subsequent visits. | 30 |
| Placebo Subjects received matched bupropion SR placebo tablet orally once daily for three days followed by twice daily for a total medication treatment of 12 weeks.
Subjects also received behavioral interventions, which included 35-minute counseling sessions at each of the first 2 visits (enrollment and on the quit day) and 10 minutes of smoking cessation counseling at subsequent visits. | 35 |
| Total | 65 |
Baseline characteristics
| Characteristic | Bupropion SR | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants | 35 Participants | 65 Participants |
| Age, Continuous | 24.5 years STANDARD_DEVIATION 5.56 | 27.5 years STANDARD_DEVIATION 6.52 | 26.2 years STANDARD_DEVIATION 6.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 5 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 30 Participants | 55 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 13 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 27 Participants | 22 Participants | 49 Participants |
| Region of Enrollment United States | 30 Participants | 35 Participants | 65 Participants |
| Sex: Female, Male Female | 30 Participants | 35 Participants | 65 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 35 |
| other Total, other adverse events | 14 / 30 | 8 / 35 |
| serious Total, serious adverse events | 2 / 30 | 5 / 35 |
Outcome results
Primary
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.
Time frame: During treatment: Visits 2-6 (time period between 2nd and 12th week of therapy)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bupropion SR | Change in Cigarette Craving and Total Nicotine Withdrawal Symptoms Between Groups During Medication Treatment | Craving for tobacco | 1.50 MNWS Score | Standard Deviation 1.11 |
| Bupropion SR | Change in Cigarette Craving and Total Nicotine Withdrawal Symptoms Between Groups During Medication Treatment | Total score of withdrawal excluding craving | 3.77 MNWS Score | Standard Deviation 4.27 |
| Placebo | Change in Cigarette Craving and Total Nicotine Withdrawal Symptoms Between Groups During Medication Treatment | Craving for tobacco | 2.07 MNWS Score | Standard Deviation 1.23 |
| Placebo | Change in Cigarette Craving and Total Nicotine Withdrawal Symptoms Between Groups During Medication Treatment | Total score of withdrawal excluding craving | 5.35 MNWS Score | Standard Deviation 5.14 |
Primary
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.
Time frame: Quit date, visit 2 (one week after starting the 12-week course of therapy)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bupropion SR | Change in Cigarette Craving and Total Nicotine Withdrawal Symptoms Between Groups on the Quit Date | Craving for tobacco | 2.04 MNWS Score | Standard Deviation 1.08 |
| Bupropion SR | Change in Cigarette Craving and Total Nicotine Withdrawal Symptoms Between Groups on the Quit Date | Total score of withdrawal excluding craving | 4.75 MNWS Score | Standard Deviation 4.87 |
| Placebo | Change in Cigarette Craving and Total Nicotine Withdrawal Symptoms Between Groups on the Quit Date | Craving for tobacco | 2.33 MNWS Score | Standard Deviation 1.31 |
| Placebo | Change in Cigarette Craving and Total Nicotine Withdrawal Symptoms Between Groups on the Quit Date | Total score of withdrawal excluding craving | 4.88 MNWS Score | Standard Deviation 4.61 |
Primary
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.
Time frame: Visit 6 (end of 12 weeks of medication therapy)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bupropion SR | Number of Participants With 7-day Point Prevalence Smoking Abstinence at the End of Medication Treatment (Visit 6) | 5 Participants |
| Placebo | Number of Participants With 7-day Point Prevalence Smoking Abstinence at the End of Medication Treatment (Visit 6) | 1 Participants |
Primary
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.
Time frame: End of pregnancy (visit 7) is a time period between 36.0-38.6 weeks gestation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bupropion SR | Number of Participants With 7-day Point Prevalence Smoking Abstinence at the End of Pregnancy (Visit 7) | 3 Participants |
| Placebo | Number of Participants With 7-day Point Prevalence Smoking Abstinence at the End of Pregnancy (Visit 7) | 1 Participants |