Sex Differences, Hormones & Smoking Cessation

Study Overview
=================
Brief Summary
-----------------
Data suggest that progesterone may improve smoking cessation outcomes perhaps by reducing impulsive behavior. However, the clinical literature on this topic is lacking. Therefore, in Project I we are proposing a double-blind randomized controlled trial to assess the role of exogenous progesterone on impulsivity and smoking cessation in a sample of males and females who are motivated to quit smoking.

Detailed Description
-----------------
Subjects will be stratified by sex and then randomly assigned to active progesterone (PRO) or placebo (PBO). Telephone screening and visit invitation leads to the consent process and in-person screening including medical-psychiatric evaluation for inclusion/exclusion, then randomization and medication induction, stable medication with medication reduction and final evaluation for secondary outcomes.

Official Title
-----------------
Sex Differences & Progesterone: Association With Impulsivity and Smoking Cessation

Conditions
-----------------
Tobacco Cessation

Intervention / Treatment
-----------------
* Other: Placebo
* Drug: Progesterone
* Other: Smoking Cessation Behavioral Counseling


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male 18 to 60 years old Female 18 to 50 years old Self-report regular smoking Motivated to quit smoking In stable physical/mental health Self report of regular menstrual cycles (female only) English fluency Understand the study procedures and able to provide informed consent Ability to participate fully in research elements for the duration of the trial. Exclusion Criteria: Current or recent (< 3 months) breastfeeding (females only) Current or planned pregnancy within the next three months (females only) Conditions contraindicated to progesterone treatment.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo - subjects will take 200 mg twice daily, orally (approximately 8am and 8pm) for twelve weeks starting seven days prior to the assigned quit date. They will also receive smoking cessation behavioral counseling. | Other: Placebo<br>* Placebo - subjects will take 200 mg twice daily orally (approximately 8am and 8pm) for twelve weeks starting seven days prior to the assigned quit date.<br>Other: Smoking Cessation Behavioral Counseling<br>* Subjects will receive weekly smoking cessation behavioral counseling.<br>|
| Experimental: Progesterone<br>The progesterone will be given in the form of an active micronized natural progesterone (Prometrium). All subjects will take 200 mg twice daily, orally (approximately 8am and 8pm) for twelve weeks starting seven days prior to the assigned quit date. They will also receive smoking cessation behavioral counseling. | Drug: Progesterone<br>* The progesterone will be given in the form of an active micronized natural progesterone (Prometrium). All subjects will take 200 mg twice daily orally (approximately 8am and 8pm) for twelve weeks starting seven days prior to the assigned quit date.<br>* Other names: Prometrium;Other: Smoking Cessation Behavioral Counseling<br>* Subjects will receive weekly smoking cessation behavioral counseling.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With 7-day Point Prevalence Abstinence From Smoking at Week 4 | 7-day point prevalence abstinence from smoking defined as having no slips (i.e., a puff or more from a lit cigarette) in the seven days prior to week 4 | Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With 7-day Point Prevalence Abstinence From Smoking at Weeks 8 and 12 | 7-day point prevalence abstinence from smoking defined as having no slips (i.e., a puff or more from a lit cigarette) in the seven days prior to weeks 8 and 12 | Weeks 8 and 12 | 
| Number of Participants With Prolonged Abstinence From Smoking at Weeks 4, 8 and 12 | Prolonged abstinence defined as having less than seven consecutive slips without a 24-hour period between any two slips prior to weeks 4, 8 and 12 | Weeks 4, 8 and 12 | 
| Number of Participants With Continuous Abstinence From Smoking at Week 12 | continuous abstinence defined as having no slips at all prior to week 12 | Week 12 | 
| Number of Participants With Cotinine <50 ng/mL at Weeks 4, 8 and 12 | urine cotinine <50 ng/mL at weeks 4, 8 and 12 | Weeks 4, 8 and 12 | 
| Number of Participants With Breath Carbon Monoxide ≤5 Ppm at Weeks 4, 8 and 12 | breath carbon monoxide ≤5 ppm at weeks 4, 8 and 12 | Weeks 4, 8 and 12 | 
| Average Number of Days to Relapse | Days to relapse defined as the number of days from quit date to the first day with a slip | Days 1 through 84 |