Effects of Progesterone on IV Nicotine-Induced Changes in Hormones and Subjective Ratings of Stimulant Drug Effect

The proposed clinical studies will analyze the interactions between progesterone, nicotine, alterations in endocrine hormones, mood and cardiovascular measures. It is hypothesized that the administration of progesterone at a dose that mimics luteal phase levels in normal cycling women will diminish the positive subjective effects of nicotine, as has been consistently observed for cocaine. This novel approach could have direct implications for facilitating smoking cessation treatment in women of reproductive age

Study Overview

• Status: Withdrawn
• Conditions: Nicotine Dependence
• Intervention / Treatment: Drug: Progesterone; Drug: Intravenous Nicotine

Detailed Description

These clinical studies are designed to examine the effects of progesterone on IV nicotine induced changes on anterior pituitary (ACTH, LH, and Prolactin) and adrenal hormones (DHEA and cortisol). We also plan to study norepinephrine (NE) and epinephrine (E), because nicotine stimulates rapid release of NE and E in preclinical and clinical studies. The study will examine the acute effects of progesterone on the effects of IV nicotine on the HPG axis. Progesterone's influence on the acute effects of nicotine on the gonadal steroid hormones (estradiol, testosterone, progesterone) are unknown. The effects of progesterone on nicotine induced changes on gonadal steroid hormones and the reciprocal feedback regulation by LH will also be examined. The temporal covariance of progesterone influenced hormonal changes with serum nicotine levels and nicotine-induced changes in subjective states and cardiovascular measures will be analyzed. Finally, the covariance between the effects of progesterone on nicotine-induced changes in endocrine, subjective and cardiovascular effects and the temporal concordance with increases in serum nicotine and cotinine levels will be determined.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Belmont, Massachusetts, United States, 02478
      • Alcohol and Drug Abuse Research Center at McLean Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.
• Subjects with peanut/peanut oil allergies will be excluded.
• Participants diagnosed with lactose intolerance will be excluded.
• Participants who describe themselves as seeking treatment will not be selected but will be referred to local smoking cessation programs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Female Smokers (Follicular Phase)	Drug: Progesterone; To stimulate the luteal phase of the menstrual cycle, Prometrium capsules containing 200 mg of micronized progesterone or placebo (lactose containing) capsules will be administered orally at 120 minutes before the injection of IV nicotine.; Drug: Intravenous Nicotine; Subjects will be given an IV challenge dose of nicotine or placebo in a constant volume of 2 mL on any study session day. The nicotine solutions (1.0 mg/70kg or 1.5 mg/70kg or 2.0 mg/70kg) will be administered over 1 min. This rate of drug delivery (2 mL over one minute) has been safe in our IRB-approved studies of nicotine. Most investigators have administered nicotine over 10 seconds without any adverse reactions. We concur with the IRB recommendation that the lower doses (1.0 mg/70kg; and 1.5 mg/70kg) will be administered first and the higher dose (2.0 mg/70kg) will be administered last.; Other Names: IV Nicotine
Active Comparator: Female Smokers (Luteal Phase)	Drug: Progesterone; To stimulate the luteal phase of the menstrual cycle, Prometrium capsules containing 200 mg of micronized progesterone or placebo (lactose containing) capsules will be administered orally at 120 minutes before the injection of IV nicotine.; Drug: Intravenous Nicotine; Subjects will be given an IV challenge dose of nicotine or placebo in a constant volume of 2 mL on any study session day. The nicotine solutions (1.0 mg/70kg or 1.5 mg/70kg or 2.0 mg/70kg) will be administered over 1 min. This rate of drug delivery (2 mL over one minute) has been safe in our IRB-approved studies of nicotine. Most investigators have administered nicotine over 10 seconds without any adverse reactions. We concur with the IRB recommendation that the lower doses (1.0 mg/70kg; and 1.5 mg/70kg) will be administered first and the higher dose (2.0 mg/70kg) will be administered last.; Other Names: IV Nicotine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects of Progesterone on IV nicotine hormones and mood	We are examining the effects of progesterone on IV nicotine induced changes in serum/plasma hormone levels and subjective states, as measured by a visual analog scale.	From baseline to study completion (approximately 1 year)

Collaborators and Investigators

• Sponsor: Mclean Hospital
• Investigators: Principal Investigator: Nancy K Mello, PhD, McLean Hospital

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: April 27, 2012
• First Submitted That Met QC Criteria: April 27, 2012
• First Posted (Estimated): May 1, 2012

Study Record Updates

• Last Update Posted (Actual): January 17, 2024
• Last Update Submitted That Met QC Criteria: January 15, 2024
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Progestins; Nicotine; Progesterone
• Other Study ID Numbers: 2008-p-000454