Tobacco Cessation
Conditions
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.
Interventions
OTHERPlacebo
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.
DRUGProgesterone
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.
OTHERSmoking Cessation Behavioral Counseling
Subjects will receive weekly smoking cessation behavioral counseling.
Sponsors
National Institute on Drug Abuse (NIDA)
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With 7-day Point Prevalence Abstinence From Smoking at Week 4 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Prolonged Abstinence From Smoking at Weeks 4, 8 and 12 | 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 |
| Number of Participants With Continuous Abstinence From Smoking at Week 12 | Week 12 | continuous abstinence defined as having no slips at all prior to week 12 |
| Number of Participants With 7-day Point Prevalence Abstinence From Smoking at Weeks 8 and 12 | 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 |
| Number of Participants With Breath Carbon Monoxide ≤5 Ppm at Weeks 4, 8 and 12 | Weeks 4, 8 and 12 | breath carbon monoxide ≤5 ppm at weeks 4, 8 and 12 |
| Average Number of Days to Relapse | Days 1 through 84 | Days to relapse defined as the number of days from quit date to the first day with a slip |
| Number of Participants With Cotinine <50 ng/mL at Weeks 4, 8 and 12 | Weeks 4, 8 and 12 | urine cotinine \<50 ng/mL at weeks 4, 8 and 12 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo-Males Placebo - subjects will take one placebo capsule 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. | 57 |
| Progesterone-Males Progesterone - The progesterone will be given in the form of an active micronized natural progesterone (Prometrium). 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. | 56 |
| Placebo-Females Placebo - subjects will take one placebo capsule 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. | 52 |
| Progesterone-Females Progesterone - The progesterone will be given in the form of an active micronized natural progesterone (Prometrium). 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. | 51 |
| Total | 216 |
Baseline characteristics
| Characteristic | Placebo-Males | Progesterone-Males | Placebo-Females | Progesterone-Females | Total |
|---|---|---|---|---|---|
| Age, Continuous | 36.8 years STANDARD_DEVIATION 11.8 | 37.9 years STANDARD_DEVIATION 10.6 | 36.0 years STANDARD_DEVIATION 7.8 | 37.6 years STANDARD_DEVIATION 7.4 | 37.1 years STANDARD_DEVIATION 9.6 |
| Race/Ethnicity, Customized Race (non-white) | 25 Participants | 22 Participants | 21 Participants | 20 Participants | 88 Participants |
| Race/Ethnicity, Customized Race (white) | 32 Participants | 34 Participants | 31 Participants | 31 Participants | 128 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 52 Participants | 51 Participants | 103 Participants |
| Sex: Female, Male Male | 57 Participants | 56 Participants | 0 Participants | 0 Participants | 113 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 57 | 0 / 56 | 0 / 52 | 0 / 51 |
| other Total, other adverse events | 0 / 57 | 0 / 56 | 0 / 52 | 0 / 51 |
| serious Total, serious adverse events | 0 / 57 | 1 / 56 | 0 / 52 | 0 / 51 |
Outcome results
Primary
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
Time frame: Week 4
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo-Males | Number of Participants With 7-day Point Prevalence Abstinence From Smoking at Week 4 | 12 Participants |
| Progesterone-Males | Number of Participants With 7-day Point Prevalence Abstinence From Smoking at Week 4 | 13 Participants |
| Placebo-Females | Number of Participants With 7-day Point Prevalence Abstinence From Smoking at Week 4 | 9 Participants |
| Progesterone-Females | Number of Participants With 7-day Point Prevalence Abstinence From Smoking at Week 4 | 18 Participants |
Secondary
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
Time frame: Days 1 through 84
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo-Males | Average Number of Days to Relapse | 13.3 days | Standard Deviation 23.8 |
| Progesterone-Males | Average Number of Days to Relapse | 13.4 days | Standard Deviation 25.9 |
| Placebo-Females | Average Number of Days to Relapse | 14.3 days | Standard Deviation 26.8 |
| Progesterone-Females | Average Number of Days to Relapse | 20.5 days | Standard Deviation 29.6 |
Secondary
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
Time frame: Weeks 8 and 12
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo-Males | Number of Participants With 7-day Point Prevalence Abstinence From Smoking at Weeks 8 and 12 | Week 8 | 10 Participants |
| Placebo-Males | Number of Participants With 7-day Point Prevalence Abstinence From Smoking at Weeks 8 and 12 | Week 12 | 12 Participants |
| Progesterone-Males | Number of Participants With 7-day Point Prevalence Abstinence From Smoking at Weeks 8 and 12 | Week 12 | 7 Participants |
| Progesterone-Males | Number of Participants With 7-day Point Prevalence Abstinence From Smoking at Weeks 8 and 12 | Week 8 | 10 Participants |
| Placebo-Females | Number of Participants With 7-day Point Prevalence Abstinence From Smoking at Weeks 8 and 12 | Week 8 | 10 Participants |
| Placebo-Females | Number of Participants With 7-day Point Prevalence Abstinence From Smoking at Weeks 8 and 12 | Week 12 | 12 Participants |
| Progesterone-Females | Number of Participants With 7-day Point Prevalence Abstinence From Smoking at Weeks 8 and 12 | Week 8 | 16 Participants |
| Progesterone-Females | Number of Participants With 7-day Point Prevalence Abstinence From Smoking at Weeks 8 and 12 | Week 12 | 20 Participants |
Secondary
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
Time frame: Weeks 4, 8 and 12
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo-Males | Number of Participants With Breath Carbon Monoxide ≤5 Ppm at Weeks 4, 8 and 12 | Week 4 | 17 Participants |
| Placebo-Males | Number of Participants With Breath Carbon Monoxide ≤5 Ppm at Weeks 4, 8 and 12 | Week 12 | 9 Participants |
| Placebo-Males | Number of Participants With Breath Carbon Monoxide ≤5 Ppm at Weeks 4, 8 and 12 | Week 8 | 14 Participants |
| Progesterone-Males | Number of Participants With Breath Carbon Monoxide ≤5 Ppm at Weeks 4, 8 and 12 | Week 4 | 20 Participants |
| Progesterone-Males | Number of Participants With Breath Carbon Monoxide ≤5 Ppm at Weeks 4, 8 and 12 | Week 8 | 13 Participants |
| Progesterone-Males | Number of Participants With Breath Carbon Monoxide ≤5 Ppm at Weeks 4, 8 and 12 | Week 12 | 14 Participants |
| Placebo-Females | Number of Participants With Breath Carbon Monoxide ≤5 Ppm at Weeks 4, 8 and 12 | Week 12 | 20 Participants |
| Placebo-Females | Number of Participants With Breath Carbon Monoxide ≤5 Ppm at Weeks 4, 8 and 12 | Week 4 | 18 Participants |
| Placebo-Females | Number of Participants With Breath Carbon Monoxide ≤5 Ppm at Weeks 4, 8 and 12 | Week 8 | 16 Participants |
| Progesterone-Females | Number of Participants With Breath Carbon Monoxide ≤5 Ppm at Weeks 4, 8 and 12 | Week 12 | 19 Participants |
| Progesterone-Females | Number of Participants With Breath Carbon Monoxide ≤5 Ppm at Weeks 4, 8 and 12 | Week 8 | 17 Participants |
| Progesterone-Females | Number of Participants With Breath Carbon Monoxide ≤5 Ppm at Weeks 4, 8 and 12 | Week 4 | 22 Participants |
Secondary
Number of Participants With Continuous Abstinence From Smoking at Week 12
continuous abstinence defined as having no slips at all prior to week 12
Time frame: Week 12
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo-Males | Number of Participants With Continuous Abstinence From Smoking at Week 12 | 4 Participants |
| Progesterone-Males | Number of Participants With Continuous Abstinence From Smoking at Week 12 | 4 Participants |
| Placebo-Females | Number of Participants With Continuous Abstinence From Smoking at Week 12 | 2 Participants |
| Progesterone-Females | Number of Participants With Continuous Abstinence From Smoking at Week 12 | 8 Participants |
Secondary
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
Time frame: Weeks 4, 8 and 12
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo-Males | Number of Participants With Cotinine <50 ng/mL at Weeks 4, 8 and 12 | Week 4 | 9 Participants |
| Placebo-Males | Number of Participants With Cotinine <50 ng/mL at Weeks 4, 8 and 12 | Week 12 | 6 Participants |
| Placebo-Males | Number of Participants With Cotinine <50 ng/mL at Weeks 4, 8 and 12 | Week 8 | 7 Participants |
| Progesterone-Males | Number of Participants With Cotinine <50 ng/mL at Weeks 4, 8 and 12 | Week 4 | 11 Participants |
| Progesterone-Males | Number of Participants With Cotinine <50 ng/mL at Weeks 4, 8 and 12 | Week 12 | 9 Participants |
| Progesterone-Males | Number of Participants With Cotinine <50 ng/mL at Weeks 4, 8 and 12 | Week 8 | 8 Participants |
| Placebo-Females | Number of Participants With Cotinine <50 ng/mL at Weeks 4, 8 and 12 | Week 8 | 8 Participants |
| Placebo-Females | Number of Participants With Cotinine <50 ng/mL at Weeks 4, 8 and 12 | Week 4 | 8 Participants |
| Placebo-Females | Number of Participants With Cotinine <50 ng/mL at Weeks 4, 8 and 12 | Week 12 | 9 Participants |
| Progesterone-Females | Number of Participants With Cotinine <50 ng/mL at Weeks 4, 8 and 12 | Week 4 | 10 Participants |
| Progesterone-Females | Number of Participants With Cotinine <50 ng/mL at Weeks 4, 8 and 12 | Week 12 | 10 Participants |
| Progesterone-Females | Number of Participants With Cotinine <50 ng/mL at Weeks 4, 8 and 12 | Week 8 | 10 Participants |
Secondary
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
Time frame: Weeks 4, 8 and 12
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo-Males | Number of Participants With Prolonged Abstinence From Smoking at Weeks 4, 8 and 12 | Week 4 | 15 Participants |
| Placebo-Males | Number of Participants With Prolonged Abstinence From Smoking at Weeks 4, 8 and 12 | Week 12 | 7 Participants |
| Placebo-Males | Number of Participants With Prolonged Abstinence From Smoking at Weeks 4, 8 and 12 | Week 8 | 9 Participants |
| Progesterone-Males | Number of Participants With Prolonged Abstinence From Smoking at Weeks 4, 8 and 12 | Week 4 | 11 Participants |
| Progesterone-Males | Number of Participants With Prolonged Abstinence From Smoking at Weeks 4, 8 and 12 | Week 12 | 6 Participants |
| Progesterone-Males | Number of Participants With Prolonged Abstinence From Smoking at Weeks 4, 8 and 12 | Week 8 | 7 Participants |
| Placebo-Females | Number of Participants With Prolonged Abstinence From Smoking at Weeks 4, 8 and 12 | Week 8 | 8 Participants |
| Placebo-Females | Number of Participants With Prolonged Abstinence From Smoking at Weeks 4, 8 and 12 | Week 4 | 10 Participants |
| Placebo-Females | Number of Participants With Prolonged Abstinence From Smoking at Weeks 4, 8 and 12 | Week 12 | 7 Participants |
| Progesterone-Females | Number of Participants With Prolonged Abstinence From Smoking at Weeks 4, 8 and 12 | Week 4 | 18 Participants |
| Progesterone-Females | Number of Participants With Prolonged Abstinence From Smoking at Weeks 4, 8 and 12 | Week 12 | 13 Participants |
| Progesterone-Females | Number of Participants With Prolonged Abstinence From Smoking at Weeks 4, 8 and 12 | Week 8 | 15 Participants |