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Placebo-controlled Trial of Bupropion for Smoking Cessation in Pregnant Women (BIBS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02188459
Recruitment Status : Completed
First Posted : July 11, 2014
Last Update Posted : February 17, 2020
Sponsor:
Information provided by (Responsible Party):
Henry Kranzler, University of Pennsylvania

Brief 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.


Condition or disease Intervention/treatment Phase
Smoking Nicotine Dependence Drug: Bupropion Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 129 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Placebo-controlled Trial of Bupropion for Smoking Cessation in Pregnant Women
Actual Study Start Date : October 30, 2014
Actual Primary Completion Date : January 22, 2020
Actual Study Completion Date : January 22, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Bupropion
Bupropion 150 mg BID, PO for 10 weeks
Drug: Bupropion
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.
Other Name: Wellbutrin

Placebo Comparator: Placebo
Placebo BID, PO for 10 weeks. The formulation appears identical to the bupropion capsules.
Drug: Bupropion
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.
Other Name: Wellbutrin




Primary Outcome Measures :
  1. Number of cigarettes smoked by medication group over 10 week treatment phase. [ Time Frame: 10 Week study period ]
    Number of cigarettes smoked for each participant during the study period. Participants will be considered to be abstinent if they self-report abstinence (not even a puff of a cigarette) for >7 days prior to the assessment after 10 weeks of treatment and at 24 weeks post-To Quit Day and have a CO <10 ppm at that time. As per convention, participants are assumed to be smoking if they self-report to be smoking at the time point, cannot be reached to provide data at the time point, fail to provide a breath sample at the time point, or provide a breath sample at the time point that has a CO concentration >10 ppm.

  2. Frequency of moderate or severe side effects. [ Time Frame: 10 week treatment phase ]
    For adverse effects, our primary outcome will be the frequency of moderate or severe side effects from a checklist of bupropion-related side effects (derived from completed bupropion studies), as well as those elicited with open-ended questions, through regular obstetrics visits, and assessments triggered by any pregnancy-related complication. Adverse effects will be systematically assessed by study personnel at 5 time points over the course of the 10-week study and can trigger dose reductions or suspension of medication.

  3. Birth outcomes obtained from clinical records. [ Time Frame: Postpartum ]
    Birth outcomes obtained from labor and delivery records (permission for which will be included in the informed consent form) will include gestational age, overall and spontaneous preterm birth (i.e., at less than 37 weeks), infant birth weight, whether small for gestational age (i.e., <10th percentile birth weight for gestational age as determined by the Alexander curve), head circumference, Apgar scores, and NICU admissions. Obstetric complications will include type of delivery and delivery and postpartum complications.


Secondary Outcome Measures :
  1. Smoking frequency after 10 weeks treatment phase. [ Time Frame: Post treatment days to 24 weeks post quit date ]
    Secondary smoking cessation outcomes include: smoking rate after 10 weeks of treatment and at 24 weeks post-TQD for non-abstainers, prolonged abstinence to weeks 10 and 24 (defined below), continuous abstinence at weeks 10 and 24 (defined below), time to 7-day relapse (no grace period), and lapse and recovery events.


Other Outcome Measures:
  1. Safety Endpoint [ Time Frame: 10 week treatment phase ]
    Participants with severe psychological symptoms (e.g., suicidal thoughts), experiencing a serious adverse event that the Principal Investigator believes to be related to study drug and a potential threat to the health and safety of the participant or fetus will be withdrawn from the study.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02188459


Locations
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United States, Delaware
Christiana Care Health System
Newark, Delaware, United States, 19713
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
Sponsors and Collaborators
Henry Kranzler
Investigators
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Principal Investigator: Henry R Kranzler, M.D. University of Pennsylvania
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Responsible Party: Henry Kranzler, M.D., University of Pennsylvania
ClinicalTrials.gov Identifier: NCT02188459    
Other Study ID Numbers: 820364
First Posted: July 11, 2014    Key Record Dates
Last Update Posted: February 17, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Tobacco Use Disorder
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Bupropion
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Cytochrome P-450 CYP2D6 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors