Placebo-controlled Trial of Bupropion for Smoking Cessation in Pregnant Women
Condition: Smoking; Nicotine Dependence
MeSH terms: Tobacco Use Disorder
Intervention: Bupropion
Intervention description: A total of 360 participants will be randomly assigned to one of two treatment conditions: Bupropion 300 mg/day (n = 180) or placebo (n = 180). We will use small-block randomization by site (Penn). A PHQ-9 score of 10 or greater will be used to identify major depression and stratify the randomization on it. Study site (Penn) will be the second of the two stratification variables.
Intervention MeSH terms: Bupropion
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 129.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Smoking during pregnancy adversely affects the health of the mother and her developing baby.
      Maternal smoking approximately doubles the risk of miscarriage, placental complications,
      preterm delivery, low birth weight and fetal and newborn death. The most common adverse
      effect of smoking during pregnancy is low birth weight, which sharply increases the risk of
      the newborn becoming ill or dying. In the US, maternal smoking is responsible for 30% of low
      birth weight babies, 10% of premature deliveries, and 5% of infant deaths. Fortunately,
      smoking cessation by pregnancy week 16, or as late as the third trimester, results in a
      near-normal weight infant at birth. Even reductions in smoking increase birth weight.

      Despite the known risks, the majority of women who are smoking at the time of their first
      prenatal visit continue to smoke. Bupropion is approved by the US Food and Drug
      Administration (FDA) for smoking cessation in people who are not pregnant, but there are no
      carefully controlled studies on the use of Bupropion to help pregnant women quit smoking.
      Bupropion is also FDA approved to treat depression, and some pregnant women have taken it for
      that purpose, even though it has not been formally tested. The investigators propose to
      conduct a randomized, parallel-group, double-blinded, placebo-controlled, 10 week trial of
      Bupropion in 360 pregnant women who smoke daily and wish to quit smoking.

      The study has three primary hypotheses. First, the investigators hypothesize that Bupropion
      treated subjects will decrease the frequency of smoking more than placebo-treated subjects.
      Second the investigators hypothesize that Bupropion treated subjects will have greater
      positive pregnancy and child health outcomes than placebo-treated subjects. Third the
      investigators hypothesize that Bupropion treated subjects will have decreased frequency of
      depressive symptoms and cigarette craving than placebo-treated subjects. These finding will
      provide information on the safety and efficacy of bupropion treat for smoking cessation in
      pregnant women.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Currently smoking on average 3 or more cigarettes per day for the preceding 7 days
             with a breath CO of at least 5 ppm and wants to quit smoking

          2. Pregnant at 13-26 weeks gestation (to maximize safety and the likelihood of receiving
             10 weeks of treatment)

          3. >18 years of age

          4. Able to speak and read English at a 6th grade level or higher, using the Slosson Oral
             Reading Test (SORT)

          5. Committed to remaining in the geographic area for at least 3 months postpartum

          6. Able to sign written informed consent and commit to completing the procedures involved
             in the study.

          7. Methadone or buprenorphine-maintained women must be in methadone or buprenorphine
             treatment for a minimum of 2 weeks prior to entering the study. Their 2 most recent
             urine drug screens, consecutive and administered at least one week apart, must both be
             positive for methadone or buprenorphine and negative for drugs of abuse other than
             cannabis. Participants who screen positive for other drugs at either time point will
             not be enrolled in the study until they meet this criterion.

        Exclusion Criteria:

          1. During the last 90 days from screening visit, meets any criteria for a DSM-IV
             diagnosis of drug or alcohol dependence-excluding tobacco or cannabis dependence and,
             for methadone or buprenorphine maintenance patients, opioid dependence-AND either
             evidences ongoing use of illicit drugs other than cannabis or continues to abuse or
             misuse prescription drugs such as CNS stimulants.

          2. Pregnant with triplets or higher order multiple gestations

          3. Has an unstable psychiatric disorder (i.e., suicide risk moderate or severe, as
             reflected by a score of >9 on the MINI Section B (Suicidality) or a suicide attempt
             during the preceding year, psychiatric hospitalization within the last 3 months;
             current psychotic disorder based on the MINI)

          4. Current or past Bipolar Disorder as determined by a study psychiatrist or psychologist
             based on assessment with the MINI, relevant information from the medical record and,
             when warranted, direct clinical evaluation.

          5. Current, regular use of psychotropic medication, inhibitors of CYP2B6 (e.g.,
             ticlopidine, clopidogrel), inducers of CYP2B6 (e.g., ritonavir, lopinavir, efavirenz),
             anticonvulsants (e.g., carbamazepine, phenobarbital, phenytoin), beta-blockers (e.g.,
             metoprolol), Type 1C antiarrhythmics (e.g., propafenone and flecainide), drugs that
             require metabolic activation by CYP2D6 to be effective (e.g., tamoxifen), drugs that
             lower seizure threshold (e.g., antipsychotics, tricyclic antidepressants,
             theophylline, or systemic corticosteroids), levodopa or amantadine

          6. Current unstable medical problems or potential inability to tolerate study treatment
             [e.g., threatened abortion: current persistent hyperemesis gravidarum (HEG) requiring
             intravenous fluids (to be rescreened when HEG is stabilized/resolved and no
             electrolyte abnormalities are evident); hypertension with evidence of end organ
             dysfunction or on more than 2 medications at the start of the pregnancy];
             arteriovenous malformation; AIDS; laboratory evidence of hepatic impairment (e.g.
             viral hepatitis with serum transaminase levels more than twice the upper limit of
             normal) ; renal impairment (e.g., elevated creatinine or creatinine clearance
             <75cc/hr), metabolic disorders (e.g., hypoglycemia, hyponatremia) or end organ damage
             from any chronic medical condition (e.g. abnormal pulmonary function tests), glaucoma,
             or other significant medical problems that in the opinion of a study obstetrician
             makes the risk of study participation unacceptable.

          7. Known major fetal congenital malformation-as determined by the study
             obstetrician-diagnosed prior to study randomization

          8. History of seizure disorder

          9. Current use of a smoking cessation medication in addition to the study medication,
             such as nicotine replacement therapy

         10. Current or history of bulimia or anorexia nervosa

         11. Current use of tobacco products other than cigarettes (e.g., E-cigarettes)

         12. Current clinically significantly abnormal laboratory evaluations that are not
             adequately controlled by standard of care treatment.

         13. History of severe head injury (i.e., with loss of consciousness)

         14. Any medical condition or concomitant medication that could compromise subject safety
             or treatment, as determined by the Principal Investigator and/or Study Physician.

         15. Inability to provide informed consent or judged by the Principal Investigator and/or
             Study Physician to be an unsuitable candidate for a clinical drug trial.