Progesterone Augmentation of Nicotine Replacement Therapy Study

NCT ID: NCT02685072

Last Updated: 2019-07-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-04-07
• Study Completion Date: 2018-03-12

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.

Conditions

Smoking Cessation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

TNP + Progesterone

Transdermal Nicotine Patch + Progesterone (200 mgs BID)

Group Type: EXPERIMENTAL

Progesterone (200 mgs BID)

Intervention Type: DRUG

Transdermal Nicotine Patch (TNP) + Progesterone

TNP + Placebo

Transdermal Nicotine Patch + Placebo (for Progesterone)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

TNP + Placebo

Interventions

Progesterone (200 mgs BID)

Transdermal Nicotine Patch (TNP) + Progesterone

Intervention Type: DRUG

Placebo

TNP + Placebo

Intervention Type: DRUG

Other Intervention Names

Prometrium

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kimberly Yonkers, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Yale School of Medicine, Department of Psychiatry

New Haven, Connecticut, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

R21CA198187

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1504015618

Identifier Type: -

Identifier Source: org_study_id