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Progesterone Augmentation of Nicotine Replacement Therapy Study (PANS)

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ClinicalTrials.gov Identifier: NCT02685072
Recruitment Status : Recruiting
First Posted : February 18, 2016
Last Update Posted : January 17, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Yale University

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.

Condition or disease Intervention/treatment Phase
Smoking Cessation Drug: Progesterone (200 mgs BID) Drug: Placebo Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Progesterone Augmentation of Nicotine Replacement Therapy Study
Actual Study Start Date : April 7, 2016
Estimated Primary Completion Date : July 2018
Estimated Study Completion Date : September 1, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: TNP + Progesterone
Transdermal Nicotine Patch + Progesterone (200 mgs BID)
Drug: Progesterone (200 mgs BID)
TNP + Progesterone
Other Name: Prometrium

Placebo Comparator: TNP + Placebo
Transdermal Nicotine Patch + Placebo (for Progesterone)
Drug: Placebo
TNP + Placebo




Primary Outcome Measures :
  1. 7-day point prevalence of smoking abstinence [ Time Frame: 8 weeks ]
    The 7-day point prevalence is defined by self-reported smoking abstinence for the last 7 days.


Secondary Outcome Measures :
  1. Carbon monoxide <10 ppm [ Time Frame: end of 8 weeks of treatment ]
    Smoking abstinence measured by breath CO

  2. Carbon monoxide <10 ppm [ Time Frame: 1 month follow up ]
    Smoking abstinence measured by breath CO

  3. Carbon monoxide <10 ppm [ Time Frame: 3 month follow up ]
    Smoking abstinence measured by breath CO

  4. Change in Stroop measure of inhibitory function [ Time Frame: Week 2 ]
    Week 2 minus baseline. The main outcome measures for the Stroop test are throughput and interference score. This test assesses processing speed, selective attention, and interference. It is a computerized version of the classical Stroop Test. The Stroop design consists of one three-minute block of congruent stimuli, and one three-minute block of incongruent stimuli.

  5. Change in Go/No Go task measure of inhibitory function [ Time Frame: 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".

  6. Change in Digit Symbol Task measure of inhibitory function [ Time Frame: Week 2 ]
    Week 2 minus baseline. The DSST is a test of psychomotor performance, which measures motor persistence, sustained attention, response speed and visuomotor coordination. The task is to fill in blank spaces with the symbols that are paired with the number above the blank space as fast as possible for 90 sec. DSST was chosen because several studies have demonstrated its sensitivity to opioid effects

  7. Positive and Negative Affect Schedule (PANAS) Total Score [ Time Frame: Week 1 ]
    Participants in the PANAS are required to respond to a 20-item test using 5-point scale that ranges from very slightly or not at all (1) to extremely (5). The total range is from 1 to 100.

  8. Positive and Negative Affect Schedule (PANAS) Total Score [ Time Frame: Week 2 ]
    Participants in the PANAS are required to respond to a 20-item test using 5-point scale that ranges from very slightly or not at all (1) to extremely (5). The total range is from 1 to 100.

  9. Positive and Negative Affect Schedule (PANAS) Total Score [ Time Frame: Week 3 ]
    Participants in the PANAS are required to respond to a 20-item test using 5-point scale that ranges from very slightly or not at all (1) to extremely (5). The total range is from 1 to 100.

  10. Positive and Negative Affect Schedule (PANAS) Total Score [ Time Frame: Week 4 ]
    Participants in the PANAS are required to respond to a 20-item test using 5-point scale that ranges from very slightly or not at all (1) to extremely (5). The total range is from 1 to 100.

  11. Positive and Negative Affect Schedule (PANAS) Total Score [ Time Frame: Week 5 ]
    Participants in the PANAS are required to respond to a 20-item test using 5-point scale that ranges from very slightly or not at all (1) to extremely (5). The total range is from 1 to 100.

  12. Positive and Negative Affect Schedule (PANAS) Total Score [ Time Frame: Week 6 ]
    Participants in the PANAS are required to respond to a 20-item test using 5-point scale that ranges from very slightly or not at all (1) to extremely (5). The total range is from 1 to 100.

  13. Positive and Negative Affect Schedule (PANAS) Total Score [ Time Frame: Week 7 ]
    Participants in the PANAS are required to respond to a 20-item test using 5-point scale that ranges from very slightly or not at all (1) to extremely (5). The total range is from 1 to 100.

  14. Positive and Negative Affect Schedule (PANAS) Total Score [ Time Frame: Week 8 ]
    Participants in the PANAS are required to respond to a 20-item test using 5-point scale that ranges from very slightly or not at all (1) to extremely (5). The total range is from 1 to 100.

  15. Positive and Negative Affect Schedule (PANAS) Total Score [ Time Frame: 9 weeks ]
    Participants in the PANAS are required to respond to a 20-item test using 5-point scale that ranges from very slightly or not at all (1) to extremely (5). The total range is from 1 to 100.

  16. Positive and Negative Affect Schedule (PANAS) Total Score [ Time Frame: 1 month follow up ]
    Participants in the PANAS are required to respond to a 20-item test using 5-point scale that ranges from very slightly or not at all (1) to extremely (5). The total range is from 1 to 100.

  17. Positive and Negative Affect Schedule (PANAS) Total Score [ Time Frame: 3 month follow up ]
    Participants in the PANAS are required to respond to a 20-item test using 5-point scale that ranges from very slightly or not at all (1) to extremely (5). The total range is from 1 to 100.

  18. Prolonged Abstinence follow up [ Time Frame: 3 months ]
    Abstinence from 2 weeks post quit date to 3 month follow up (total of 3 months during the trial and 3 month follow up)

  19. Prolong Abstinence post trial [ Time Frame: 3 months ]
    Abstinence from 2 weeks post quit date to the one month follow up



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02685072


Contacts
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Contact: Marla Genova, MA 203-764-8124

Locations
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United States, Connecticut
Yale School of Medicine, Department of Psychiatry Recruiting
New Haven, Connecticut, United States, 06510
Contact: Marla Genova, M.A.    203-764-8124    MARLA.GENOVA@YALE.EDU   
Principal Investigator: Kimberly A Yonkers, M.D.         
Sponsors and Collaborators
Yale University
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Kimberly Yonkers, MD Yale School of Medicine

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Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT02685072     History of Changes
Other Study ID Numbers: 1504015618
R21CA198187 ( U.S. NIH Grant/Contract )
First Posted: February 18, 2016    Key Record Dates
Last Update Posted: January 17, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: we will only make aggregate de-identified data available

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Yale University:
Smoking Cessation
Nicotine Cessation

Additional relevant MeSH terms:
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Progesterone
Nicotine
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Progestins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists