Effects of Progesterone on Smoked Nicotine Induced Changes in Hormones and Subjective Ratings of Stimulant Drug Effects

This study has suspended participant recruitment.
(Clinical studies are stopped, pending funding)
Sponsor:
Information provided by (Responsible Party):
Nancy Kishlar Mello, Mclean Hospital
ClinicalTrials.gov Identifier:
NCT01636336
First received: June 21, 2012
Last updated: January 14, 2013
Last verified: January 2013
  Purpose

The clinical studies propose to study the abuse-related effects of nicotine after progesterone administration during the follicular phase in women of reproductive age. Concurrent analysis of hypothalamic-pituitary-adrenal hormones should help to clarify the role of the HPA axis in the abuse-related effects of nicotine.


Condition Intervention
Nicotine Dependence
Other: Nicotine
Other: Progesterone

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)

Resource links provided by NLM:


Further study details as provided by Mclean Hospital:

Primary Outcome Measures:
  • Effects of Progesterone on Nicotine-Induced Changes on the hypothalamic-pituitary adrenal (HPA) axis [ Time Frame: From baseline to study completion (approximately 8 months for females) ] [ Designated as safety issue: No ]
    The investigators are examining the effects of progesterone on smoked nicotine induced changes in serum/plasma hormone levels.

  • Effects of Nicotine on the hypothalamic-pituitary-gonadal (HPG) axis [ Time Frame: From baseline to study completion (approximately 8 months for females) ] [ Designated as safety issue: No ]
    The investigators are examining the effects of smoked nicotine on serum nicotine levels and serum/plasma hormone levels.


Secondary Outcome Measures:
  • Effects of Nicotine on a Visual Analog Scale of Mood States [ Time Frame: From baseline to study completion (approximately 8 months for females) ] [ Designated as safety issue: No ]
    The investigators are examining the effects of progesterone on smoked nicotine induced changes in subjective states ("high," "like," "rush," "dizzy," etc.), as measured by a visual analog scale.

  • Effects of Nicotine on Cardiovascular Measures [ Time Frame: From baseline to study completion (approximately 8 months for females) ] [ Designated as safety issue: No ]
    The investigators are examining the effects of progesterone on smoked nicotine induced changes in cardiovascular measures, as measured by blood pressure and heart rate.


Estimated Enrollment: 45
Study Start Date: September 2008
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Female Smokers (Mid-Luteal Phase; cycle days 18-22) Other: Nicotine
Two doses of nicotine will be utilized in the study: a commercially available, high-yield nicotine cigarette (Marlboro Red; Phillip Morris brand) and a denicotinized cigarette (Murty Pharmaceuticals Inc., Lexington, KY). The high dose cigarettes contain 15.48 mg of nicotine and 16 mg of tar based on analysis by the Massachusetts Department of Public Health (MDPH, 1998). The low nicotine cigarettes contain 1.1 mg of nicotine and deliver 0.1 mg of nicotine and 2.8 mg of tar based on analyses provided by the manufacturer.
Other: Progesterone
Prometrium capsules containing 200 mg of micronized progesterone will be obtained from Solvay Pharmaceuticals, Inc. (210 Main Street West, Baudette, MN, 56623, phone (218) 634-3500, fax (218) 634-3540).
Active Comparator: Female Smokers (Early Follicular Phase; cycle days 4-8) Other: Nicotine
Two doses of nicotine will be utilized in the study: a commercially available, high-yield nicotine cigarette (Marlboro Red; Phillip Morris brand) and a denicotinized cigarette (Murty Pharmaceuticals Inc., Lexington, KY). The high dose cigarettes contain 15.48 mg of nicotine and 16 mg of tar based on analysis by the Massachusetts Department of Public Health (MDPH, 1998). The low nicotine cigarettes contain 1.1 mg of nicotine and deliver 0.1 mg of nicotine and 2.8 mg of tar based on analyses provided by the manufacturer.
Other: Progesterone
Prometrium capsules containing 200 mg of micronized progesterone will be obtained from Solvay Pharmaceuticals, Inc. (210 Main Street West, Baudette, MN, 56623, phone (218) 634-3500, fax (218) 634-3540).

Detailed Description:

These clinical studies will analyze the interactions between progesterone, nicotine, alterations in endocrine hormones, mood and cardiovascular measures. The studies also intend to examine the contribution of menstrual cycle phase. It is hypothesized that this novel focus on nicotine's rapid hormonal, cardiovascular and subjective effects will be important for developing novel biologic approaches to treatment for nicotine abuse and dependence as well as advancing our understanding of the neurobiology of nicotine reinforcement.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Women between the ages of 18 and 40 who currently smoke at least 15 cigarettes every day, and who fulfill DSM-IV diagnostic criteria for nicotine dependence will be eligible for participation.
  • No evidence of clinically significant disease based upon complete medical history and physical examination supervised by Dr. Arthur Siegel (Chief of Internal Medicine).
  • Absence of DSM-IV Axis I Disorders other than nicotine dependence (305.10) as measured by the Structured Clinical Interview (SCID).
  • Routine laboratory blood tests including complete blood count, electrolytes, BUN and creatinine, liver function tests, hepatitis panel and urinalysis will be performed. Laboratory parameters must be within the normal range. HBsAg must be negative but subjects who have hepatitis serology consistent with previous exposure to Hepatitis A, Hepatitis B, or Hepatitis C, but who do not have clinical and biochemical evidence of acute infection, will be acceptable.
  • Hematocrit levels ≥ 35% for females.
  • Serum pregnancy test (hCG beta subunit) results must be negative within 24 hrs of the study session day.
  • Normal EKG.
  • A Body Mass Index (BMI—ratio of weight (W) to height (H) squared; W/H2=kg/m2) of between 18.0 and 27.0 for women.
  • Subjects must be able to read and understand instructions, as well as provide a valid informed consent.

Exclusion Criteria:

  • Participants with any lifetime DSM-IV Axis I disorder other than nicotine dependence.
  • Participants with clinically significant medical disorders.
  • Women who are pregnant as determined by laboratory testing for serum beta hCG.
  • Women who use hormonal contraceptive medications will not be accepted, because this would confound the hormonal measures.
  • Women with a mean BMI of outside the range 18.0-27.0.
  • Participants who describe themselves as seeking treatment will not be selected but will be referred to local smoking cessation programs.
  • Subjects with peanut/peanut oil allergies will be excluded.
  • Participants diagnosed with lactose intolerance will be excluded.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01636336

Locations
United States, Massachusetts
Alcohol and Drug Abuse Research Center at McLean Hospital
Belmont, Massachusetts, United States, 02478
Sponsors and Collaborators
Mclean Hospital
Investigators
Principal Investigator: Nancy K Mello, PhD Mclean Hospital
  More Information

No publications provided

Responsible Party: Nancy Kishlar Mello, Director, Alcohol and Drug Abuse Research Center & Professor of Psychology (Neuroscience), Harvard Medical School, Mclean Hospital
ClinicalTrials.gov Identifier: NCT01636336     History of Changes
Other Study ID Numbers: 2009-p-001665
Study First Received: June 21, 2012
Last Updated: January 14, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Tobacco Use Disorder
Substance-Related Disorders
Mental Disorders
Nicotine
Nicotine polacrilex
Progesterone
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Central Nervous System Stimulants
Central Nervous System Agents
Therapeutic Uses
Progestins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on July 26, 2014