Official Title: “Progesterone and the Effects of Nicotine”

Past research on nicotine addiction has shown that changes in estradiol and progesterone hormone levels during menstruation may cause women to respond differently than men to nicotine. The purpose of this study is to examine the effects of progesterone on smoking behavior, nicotine withdrawal symptoms, and the reinforcing effects of smoking in men and women addicted to nicotine.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: June 2008

Nicotine addiction is a serious health problem. Almost 35 million people in the United States try to quit smoking each year, but less than 7 percent are successful. Many smokers report a "high" sensation, followed by a feeling of relaxation. Such positive reinforcement factors, combined with nicotine cravings, make it difficult to stop the use of nicotine products. Past research has suggested that women may experience fewer nicotine cravings and may be less affected by smoking's positive reinforcement factors when compared to men. Fluctuations in levels of the female hormones estradiol and progesterone during menstruation may play a role in determining how women are affected by nicotine. The purpose of this study is to examine the effects of a controlled oral dose of progesterone on smoking behavior, nicotine withdrawal symptoms, and nicotine-related positive reinforcement factors in nicotine dependent males and females.

In this 4-day study, participants will be randomly assigned to receive a daily dose of 200 mg of progesterone, 400 mg of progesterone, or placebo. All participants will abstain from smoking for Days 1 through 3. On Day 4, participants will take part in a smoking session, during which their smoking habits, including the number of puffs, duration of puffs, and number of cigarettes smoked, will be measured. Outcome measurements will include self-reports of cravings; carbon monoxide monitoring; and standardized questionnaires to assess nicotine withdrawal symptoms.

This study has been completed with 35 men and 30 women. With the final women completing in March of 2008. Currently in Data Analysis phase

Intervention(s) in this Clinical Trial

• Drug: Progesterone
  • Progesterone will be given on the first day of menstruation for a duration of four days.

Primary Measures

• Smoking topography; measured by carbon monoxide levels and self-report at Day 4
  • Time Frame: 4 years anticipated
    Safety Issue?: No
• Nicotine withdrawal symptoms; measured by the Minnesota Nicotine Withdrawal Scale at Day 4
  • Time Frame: Anticipated 4 year study
    Safety Issue?: No

Inclusion Criteria:

• History of smoking 10-25 cigarettes daily for the past 12 months
• Score of at least 5 on the Fagerström Nicotine Tolerance Questionnaire
• Carbon monoxide level greater than 10 ppm
• Body mass index between 19 to 36
• Currently in good health, as determined by medical history, screening examination, and laboratory tests
• If female, regular menstrual cycle every 25 to 35 days
• If female, willing to use non-hormonal contraception throughout the study

Exclusion Criteria:

• Seeking treatment for nicotine dependence
• History of major medical illness, including liver disease; abnormal vaginal bleeding;
• suspected or known tumors; thrombophlebitis; deep vein thrombosis; pulmonary embolus;
• clotting or bleeding disorders; heart disease; diabetes; stroke; or other medical conditions that are considered unsafe for study participants by the investigator
• Regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics)
• Recent diagnosis and treatment for Axis I disorders, including major depression, bipolar affective disorder, schizophrenia, or panic disorder
• Currently abusing alcohol or other recreational or prescription drugs
• Current use of any tobacco products other than cigarettes, including smokeless tobacco and nicotine products
• Known allergy to progesterone
• Known allergy to peanuts
• If female, amenorrhea
• Pregnant or breastfeeding

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 40 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute on Drug Abuse (NIDA)

Overall Clinical Trial Officials and Contacts

Mehmet Sofuoglu, PhD Principal Investigator Yale University, Department of Psychiatry  

Overall Contact: Lance Barnes 203-937-4823 lance.barnes@yale.edu

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00271206

Study ID Number: R01DA14537

ClinicalTrials.gov Identifier: NCT00271206

Health Authority: United States: Federal Government