Clinical trial NCT02685072: Progesterone Augmentation of Nicotine Replacement Therapy Study
Official title: Progesterone Augmentation of Nicotine Replacement Therapy Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Smoking Cessation
Keywords: Smoking Cessation
Nicotine Cessation
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2016-02-18
Enrollment: 64
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This will be a double-blind, placebo-controlled, pilot, randomized clinical trial. A total of 50 women who smoke and have regular menstrual cycles will be randomized to either progesterone (200 mgs BID) + Transdermal Nicotine Patch (TNP) or placebo + TNP for 8 weeks. TNP will be tapered after 4-6 weeks. Progesterone or matching placebo will be discontinued at the end of Week 8. All participants will also be provided behavioral treatment for smoking cessation. Participants will be inducted onto progesterone (or placebo) + TNP over a one-week period (Week 1) during the mid luteal phase, within a week before menses and the target quit date will be set for the 5 (+/-2) days after onset of menses. Participants will have post-trial follow-up visits at 1 and 3 months.The main study outcomes will be self- report of smoking abstinence, biochemically verified smoking abstinence, measures of cigarette craving and nicotine withdrawal, and measures of response inhibition.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 7-day Point Prevalence of Smoking Abstinence
timeFrame: end of 8 weeks of treatment
Secondary outcomes:
measure: Carbon Monoxide <10 Ppm
timeFrame: end of 8 weeks of treatment
measure: Carbon Monoxide <10 Ppm
timeFrame: 1 month follow up
measure: Carbon Monoxide <10 Ppm
timeFrame: 3 month follow up
measure: Change in Stroop Measure of Inhibitory Function
timeFrame: baseline and week 2
measure: Change in Go/No Go Task Measure of Inhibitory Function
timeFrame: baseline and week 2
measure: Change in Digit Symbol Task Measure of Inhibitory Function
timeFrame: baseline and week 2
measure: Positive and Negative Affect Schedule (PANAS) Total Score
timeFrame: Baseline
measure: Positive and Negative Affect Schedule (PANAS) Total Score
timeFrame: Week 2
measure: Positive and Negative Affect Schedule (PANAS) Total Score
timeFrame: Week 3
measure: Positive and Negative Affect Schedule (PANAS) Total Score
timeFrame: Week 4
measure: Positive and Negative Affect Schedule (PANAS) Total Score
timeFrame: Week 5
measure: Positive and Negative Affect Schedule (PANAS) Total Score
timeFrame: Week 6
measure: Positive and Negative Affect Schedule (PANAS) Total Score
timeFrame: Week 7
measure: Positive and Negative Affect Schedule (PANAS) Total Score
timeFrame: Week 8
measure: Positive and Negative Affect Schedule (PANAS) Total Score
timeFrame: 1 month follow up
measure: Positive and Negative Affect Schedule (PANAS) Total Score
timeFrame: 3 month follow up
measure: Prolonged Abstinence Post Trial
timeFrame: 1-month follow-up after end of treatment
measure: Prolonged Abstinence Follow up
timeFrame: 3-month follow-up after end of treatment
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale School of Medicine, Department of Psychiatry
state: Connecticut
Study officials:
affiliation: Yale University
name: Kimberly Yonkers, MD
role: PRINCIPAL_INVESTIGATOR
References: