- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02685072
Progesterone Augmentation of Nicotine Replacement Therapy Study (PANS)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This study seeks to determine if modifying the hormonal milieu of the menstrual cycle, through administration of exogenous progesterone, will improve the effectiveness of treatments for smoking cessation in women. Progesterone, a gonadal hormone, is used clinically for treatment of endometrial hyperplasia, amenorrhea, dysfunctional uterine bleeding, and for assisted reproduction in women. Progesterone also shows promise for the treatment of multiple central nervous system disorders including cocaine addiction, seizure disorder, and traumatic brain injury. As the next step, the investigators seek to determine if progesterone augments standard smoking cessation treatments (e.g., NRT) in regularly cycling women. The investigators hypothesize that co-treatment with progesterone, compared to placebo, will enhance the effectiveness NRT for smoking cessation. To test this hypothesis, the investigators propose an 8-week, double-blind, placebo-controlled clinical trial, which will randomize 50 smokers using a 1:1 assignment ratio to 400 mg/day progesterone or placebo. Consistent with the Clinical Practice Guidelines, all participants will also receive transdermal nicotine patch (TNP) plus brief counseling for smoking cessation during the study participation.
Specific Aim #1: To determine if progesterone +TNP is superior to placebo +TNP for prolonged and 7-day point prevalence of smoking abstinence rates at the end of 8 weeks of treatment and at 1 and 3 month follow-up time points. The investigators will also evaluate the safety and tolerability of progesterone treatment, compared to placebo. Our co-primary outcome measures will be 7-day point prevalence of smoking abstinence and breath CO at the end of treatment and 1- and 3-months after the end of the trial. Specific Aim #2: To determine if progesterone + TNP treatment, compared to placebo + TNP, improves response inhibitory function, as assessed by the Stroop, The Go/No Go task, and the Digit Symbol Task. Specific Aim # 3: To determine if progesterone + TNP treatment, compared to placebo + TNP, leads to a greater reduction in cigarette craving and nicotine withdrawal symptoms, as assessed by the Questionnaire on Smoking Urges-Brief (QSU-B) and the Minnesota Nicotine Withdrawal Scale (MNWS), respectively. Specific Aim #4: To evaluate with affective changes, as shown on the Positive and Negative Affect Schedule, mediates the effects of progesterone on smoking abstinence.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Connecticut
-
New Haven, Connecticut, United States, 06510
- Yale School of Medicine, Department of Psychiatry
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Aged 18 - 45
- Smoking at least 5 cigarettes/ day for at least one year
- Regular menstrual cycles every 24-36 days for the previous 6 months
- Motivated to quit smoking (i.e., a rating of at least "7 "on a 10-point scale where 1 is not at all motivated and 10 is extremely motivated)
- In good health
- Using an acceptable, non-hormonal birth control
Exclusion Criteria:
A history of major medical or psychological illnesses including:
- liver disease
- heart disease
- diabetes
- malignancy including history of breast cancer
- deep vein thrombosis
- blood coagulation problems including a history or family history of thrombophilia
- liver failure
- cervical intra-epithelial lesions III or greater that are untreated
- other medical conditions that the physician investigators deems will make study participation unsafe for the subject
- current or past history bipolar disorder or schizophrenia
- current diagnosis of major depression
- panic disorder or post-traumatic stress disorder
- active drug (non-nicotine) and/or alcohol dependence
- currently undergoing treatment with another pharmacological agent for smoking cessation
- regular use of sedating medications including sleeping aids, antihistamines, and others use of nicotine from cigars, pipes, chewing tobacco
- pregnant
- breast- feeding or intending to become pregnant within 6 months
- allergy to nicotine patch or progesterone
- allergy to peanuts or other nuts.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: DOUBLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: TNP + Progesterone
Transdermal Nicotine Patch + Progesterone (200 mgs BID)
|
Transdermal Nicotine Patch (TNP) + Progesterone
Other Names:
|
PLACEBO_COMPARATOR: TNP + Placebo
Transdermal Nicotine Patch + Placebo (for Progesterone)
|
TNP + Placebo
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
7-day Point Prevalence of Smoking Abstinence
Time Frame: end of 8 weeks of treatment
|
The 7-day point prevalence is defined by self-reported smoking abstinence for the last 7 days.
|
end of 8 weeks of treatment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Carbon Monoxide <10 Ppm
Time Frame: end of 8 weeks of treatment
|
Smoking abstinence measured by breath CO
|
end of 8 weeks of treatment
|
Carbon Monoxide <10 Ppm
Time Frame: 1 month follow up
|
Smoking abstinence measured by breath CO
|
1 month follow up
|
Carbon Monoxide <10 Ppm
Time Frame: 3 month follow up
|
Smoking abstinence measured by breath CO
|
3 month follow up
|
Change in Stroop Measure of Inhibitory Function
Time Frame: baseline and week 2
|
The Stroop test assesses cognitive processing.
The Level 3 Stroop Throughput score incorporates both accuracy and speed.
In Level 3 of the Stroop test, a series of words representing colors are shown in a font color that is incongruent with the word (e.g.
RED would be shown in blue font).
Users are asked to press a response key associated with the color of the font, not the written word.
Quicker and more accurate responses lead to higher scores.
The lowest possible score is 0 (no correct responses).
There is no defined maximum score, as the score depends upon both response time and number of correct responses.
A Level 3 Stroop Throughput change score was calculated by subtracting baseline score from week 2 score.
Higher positive scores represent greater improvement in scores at week 2 relative to baseline, and lower negative scores represent greater decline in scores from baseline to week 2.
|
baseline and week 2
|
Change in Go/No Go Task Measure of Inhibitory Function
Time Frame: baseline and week 2
|
Week 2 minus baseline. This task assesses the ability to withhold responses to an infrequently occurring target (No-Go trials). A total of 225 single digits (25 x 9 digits) are presented on a computer monitor for 250 ms each, immediately followed by a mask for 900 ms. Subjects must press a spacebar in response to every digit except the "3". Go/No Go score is calculated as separation between the means of the signal and the noise distributions and is reported in standard deviation units, representing an overall indicator of performance since it accounts for correct responses and incorrect responses. Higher scores represent a better outcome. For the change score, higher positive scores represent greater improvement in scores between baseline and week 2, and lower negative scores represent greater decline in scores between baseline and week 2. |
baseline and week 2
|
Change in Digit Symbol Task Measure of Inhibitory Function
Time Frame: baseline and week 2
|
The Code Substitution Test (a computerized adaptation/variant of the Digit Symbol Substitution Test) is a test of psychomotor performance.
The Code Substitution-Learning Throughput Score incorporates both accuracy and speed.
During the learning phase of this test, users are continuously shown a row of 9 digits that are paired with a symbol (the pairings are constant).
Users are presented with a series of individual pairings and are asked to press a response key to indicate if the pairing is correct or not.
Quicker and more accurate responses lead to higher scores.
The lowest possible score is 0 (no correct responses).
There is no defined maximum score, as the score depends upon both response time and number of correct responses.
A change score was calculated by subtracting baseline score from week 2 score.
Higher positive scores represent greater improvement in scores at week 2 relative to baseline, and lower negative scores represent greater decline in scores from baseline to week 2.
|
baseline and week 2
|
Positive and Negative Affect Schedule (PANAS) Total Score
Time Frame: Baseline
|
The PANAS questionnaire consists of 20 items that describe different feelings and emotions.
Participants are asked to what extent they feel this way right now on 5-point scale ranging from 1 (very slightly or not at all) to 5 (extremely).
Separate Positive Affect Scores and Negative Affect Scores were calculated from 10 items each.
Scores can range from 10 t0 50, with higher scores representing higher levels of positive affect and with lower scores representing lower levels of negative affect.
|
Baseline
|
Positive and Negative Affect Schedule (PANAS) Total Score
Time Frame: Week 2
|
The PANAS questionnaire consists of 20 items that describe different feelings and emotions.
Participants are asked to what extent they feel this way right now on 5-point scale ranging from 1 (very slightly or not at all) to 5 (extremely).
Separate Positive Affect Scores and Negative Affect Scores were calculated from 10 items each.
Scores can range from 10 t0 50, with higher scores representing higher levels of positive affect and with lower scores representing lower levels of negative affect.
|
Week 2
|
Positive and Negative Affect Schedule (PANAS) Total Score
Time Frame: Week 3
|
The PANAS questionnaire consists of 20 items that describe different feelings and emotions.
Participants are asked to what extent they feel this way right now on 5-point scale ranging from 1 (very slightly or not at all) to 5 (extremely).
Separate Positive Affect Scores and Negative Affect Scores were calculated from 10 items each.
Scores can range from 10 t0 50, with higher scores representing higher levels of positive affect and with lower scores representing lower levels of negative affect.
|
Week 3
|
Positive and Negative Affect Schedule (PANAS) Total Score
Time Frame: Week 4
|
The PANAS questionnaire consists of 20 items that describe different feelings and emotions.
Participants are asked to what extent they feel this way right now on 5-point scale ranging from 1 (very slightly or not at all) to 5 (extremely).
Separate Positive Affect Scores and Negative Affect Scores were calculated from 10 items each.
Scores can range from 10 t0 50, with higher scores representing higher levels of positive affect and with lower scores representing lower levels of negative affect.
|
Week 4
|
Positive and Negative Affect Schedule (PANAS) Total Score
Time Frame: Week 5
|
The PANAS questionnaire consists of 20 items that describe different feelings and emotions.
Participants are asked to what extent they feel this way right now on 5-point scale ranging from 1 (very slightly or not at all) to 5 (extremely).
Separate Positive Affect Scores and Negative Affect Scores were calculated from 10 items each.
Scores can range from 10 t0 50, with higher scores representing higher levels of positive affect and with lower scores representing lower levels of negative affect.
|
Week 5
|
Positive and Negative Affect Schedule (PANAS) Total Score
Time Frame: Week 6
|
The PANAS questionnaire consists of 20 items that describe different feelings and emotions.
Participants are asked to what extent they feel this way right now on 5-point scale ranging from 1 (very slightly or not at all) to 5 (extremely).
Separate Positive Affect Scores and Negative Affect Scores were calculated from 10 items each.
Scores can range from 10 t0 50, with higher scores representing higher levels of positive affect and with lower scores representing lower levels of negative affect.
|
Week 6
|
Positive and Negative Affect Schedule (PANAS) Total Score
Time Frame: Week 7
|
The PANAS questionnaire consists of 20 items that describe different feelings and emotions.
Participants are asked to what extent they feel this way right now on 5-point scale ranging from 1 (very slightly or not at all) to 5 (extremely).
Separate Positive Affect Scores and Negative Affect Scores were calculated from 10 items each.
Scores can range from 10 t0 50, with higher scores representing higher levels of positive affect and with lower scores representing lower levels of negative affect.
|
Week 7
|
Positive and Negative Affect Schedule (PANAS) Total Score
Time Frame: Week 8
|
The PANAS questionnaire consists of 20 items that describe different feelings and emotions.
Participants are asked to what extent they feel this way right now on 5-point scale ranging from 1 (very slightly or not at all) to 5 (extremely).
Separate Positive Affect Scores and Negative Affect Scores were calculated from 10 items each.
Scores can range from 10 t0 50, with higher scores representing higher levels of positive affect and with lower scores representing lower levels of negative affect.
|
Week 8
|
Positive and Negative Affect Schedule (PANAS) Total Score
Time Frame: 1 month follow up
|
The PANAS questionnaire consists of 20 items that describe different feelings and emotions.
Participants are asked to what extent they feel this way right now on 5-point scale ranging from 1 (very slightly or not at all) to 5 (extremely).
Separate Positive Affect Scores and Negative Affect Scores were calculated from 10 items each.
Scores can range from 10 t0 50, with higher scores representing higher levels of positive affect and with lower scores representing lower levels of negative affect.
|
1 month follow up
|
Positive and Negative Affect Schedule (PANAS) Total Score
Time Frame: 3 month follow up
|
The PANAS questionnaire consists of 20 items that describe different feelings and emotions.
Participants are asked to what extent they feel this way right now on 5-point scale ranging from 1 (very slightly or not at all) to 5 (extremely).
Separate Positive Affect Scores and Negative Affect Scores were calculated from 10 items each.
Scores can range from 10 t0 50, with higher scores representing higher levels of positive affect and with lower scores representing lower levels of negative affect.
|
3 month follow up
|
Prolonged Abstinence Post Trial
Time Frame: 1-month follow-up after end of treatment
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Abstinence from 2 weeks post quit date to the one month follow up
|
1-month follow-up after end of treatment
|
Prolonged Abstinence Follow up
Time Frame: 3-month follow-up after end of treatment
|
Abstinence from 2 weeks post quit date to 3 month follow up (total of 6-8 weeks during the trial and 3 month follow up)
|
3-month follow-up after end of treatment
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Kimberly Yonkers, MD, Yale School of Medicine
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1504015618
- R21CA198187 (NIH)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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