Progesterone Augmentation of Nicotine Replacement Therapy Study
Condition: Smoking Cessation
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Progesterone (200 mgs BID); Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Transdermal Nicotine Patch (TNP) + Progesterone; TNP + Placebo
Other intervention name(s): Prometrium
Intervention MeSH terms: Progesterone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Smoking Cessation; Nicotine Cessation