Progesterone for Smoking Relapse Prevention Following Delivery

Study Overview
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Brief Summary
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Smoking is the main preventable cause of mortality in Western countries, contributing to over 430,000 deaths a year in the U.S. alone. Clinical and epidemiological studies show that women often decrease smoking in pregnancy, when progesterone levels are high. However, at least half resume pre-pregnancy smoking levels within weeks after delivery and when progesterone levels drop. Data from preclinical and clinical studies suggest that progesterone may be effective in preventing relapse to smoking in non-postpartum women. Prior work has shown that progesterone decreases both craving for cigarettes and the subjective rewarding effects of smoking among recently abstinent female smokers. These findings led us to hypothesize that progesterone may have efficacy as a relapse prevention treatment for postpartum women. We propose an 8-week, randomized pilot study to evaluate the safety and initial efficacy of progesterone. This will be a feasibility study that will compare progesterone to placebo for relapse prevention in 40 postpartum smokers. We will assess the feasibility and safety, including the potential effects on breastfeeding and infants exposed via breast milk, in addition to 7-day point prevalence of smoking abstinence after 8 weeks of treatment and at follow-up, 3-months after the end of the protocol.

Official Title
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Progesterone for Postpartum Smokers: Feasibility, Breastfeeding and Infant Safety

Conditions
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Tobacco Use Disorder

Intervention / Treatment
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* Drug: Progesterone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Need to be within 3 weeks of delivery because relapse to smoking happens early after childbirth Aged 18 to 42 years history of smoking, with smoking and other nicotine product abstinence achieved in the final two months of pregnancy and at delivery In good health as verified by medical history Using acceptable birth control methods other than hormonal contraceptives that contain progestins Have biologically confirmed abstinence from tobacco and other nicotine products at randomization Exclusion Criteria: A history of major medical illnesses including liver diseases, suspected or known malignancy, thrombophlebitis, liver failure, or other medical conditions that the physician investigator deems will make study participation unsafe for the subject Current or past history bipolar disorder or schizophrenia or current diagnosis of major depression, panic disorder or post-traumatic stress disorder Dependence on and/or abuse of alcohol or other drugs of abuse in the month prior to randomization into the trial the presence of suicidal or homicidal ideation, or significant impairment of social or occupational functioning, either at study baseline during the evaluation process, or during participation in the trial inability to speak Spanish or English (our group is bilingual) plans to move out of the area within 8 months after study screening since this will make follow-up difficult Inability to understand study procedures or provide informed consent Currently undergoing treatment with another pharmacological agent for smoking cessation pending legal case that may result in incarceration since this would force abstinence and impede follow-up; Pending case with child protective services that might lead removal of infant from mother's custody, as this would impede breastfeeding and infant follow-up Unwilling to accept randomization Subsequent pregnancy since that would be another source of progesterone An acute general medical condition that would require imminent re-hospitalization since this would enforce abstinence (women may be randomized if they are discharged and still within the recruitment window) Allergy to progesterone or peanuts (vehicle for micronized progesterone) Currently undergoing treatment with ketoconazole or any other known strong CYP3A4 inhibitors

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 42 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo<br>In this group women will receive a placebo pill which will appear similar to progesterone and will be inert. | Drug: Placebo<br> <br> |
| Experimental: Progesterone<br>In this group women will receive oral micronized progesterone twice a day. | Drug: Progesterone<br>* oral micronized progesterone<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of Progesterone as a Relapse Prevention Intervention for Postpartum Women With Pre-conception Smoking: Adherence to Treatment | Feasibility will be shown by high adherence to treatment condition assessed by doses of study medication taken | 8 weeks | 
| Feasibility of Progesterone as a Relapse Prevention Intervention for Postpartum Women With Pre-conception Smoking: Retention | Feasibility in retention will be shown by at least 70% of women randomized to the progesterone group reamaining in the study at the 3-month follow-up | From randomization to 3-month follow-up: up to 5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 7-day Point Prevalence of Abstinence at End of Treatment (Week 8) | Abstinence was defined as self-report of no smoking in the past 7 days confirmed by a negative urine cotinine test (urine cotinine <100 ng/ml). | Week 8 of the trial period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Progesterone, Placebo, Postpartum, Tobacco, Pregnancy