Effects of Progesterone on IV Nicotine Induced Changes on BOLD fMRI Signal, Hormones and Subjective Ratings of Stimulant Drugs

The proposed clinical studies will analyze the interactions between progesterone, nicotine, fMRI measures of patterns of brain activity, covariance with 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• Status: Withdrawn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: Intravenous Nicotine; Drug: Progesterone

Detailed Description

These clinical studies will examine the effects of progesterone on the acute effects of IV nicotine and on patterns of brain activation in areas of the brain with high levels of nicotine receptors. This will be correlated with serum nicotine levels, nicotine-induced changes in subjective states, and endocrine measures of the HPA and HPG axes. The temporal covariance of progesterone's effects on serum nicotine levels and nicotine-induced changes in subjective states and cardiovascular measures will be analyzed.

The covariance between the effects of progesterone on nicotine-induced changes in BOLD fMRI, 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:

• Men and 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 by a qualified physician.
• 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 ≥ 39% for males and ≥ 35% for females.
• Serum pregnancy test (hCG beta subunit) results must be negative within 24 hrs of the study day.
• Normal ECG.
• A Body Mass Index (BMI-ratio of weight (W) to height (H) squared; W/H2=kg/m2) of between 18 and 27 for women and 21 to 29 for men.
• Subjects must be able to read and understand instructions, as well as provide a valid informed consent.
• Individuals without hypersensitivity to peanuts or peanut oil.
• Participants without a current diagnosis of lactose intolerance. No evidence of clinically significant disease based upon complete medical history and physical examination by a qualified physician.

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 18-27 and men with a BMI outside the range 21-29.
• Participants who describe themselves as seeking treatment will not be selected but will be referred to local smoking cessation programs.
• Participants with allergies to peanuts or peanut oil.
• Participants diagnosed with lactose intolerance.

• Participants with ferromagnetic implants or other contraindications to fMRI:

  • Cardiac pacemakers
  • Metal clips on blood vessels (also called stents)
  • Artificial heart valves
  • Artificial arms, hands, legs, etc.
  • Brain stimulator devices
  • Implanted drug pumps
  • Ear implants
  • Eye implants or known metal fragments in eyes
  • Exposure to shrapnel or metal filings (wounded in military combat, sheet metal workers, welders, and others)
  • Other metallic surgical hardware in vital areas
  • Certain tattoos with metallic ink
  • Transdermal patches (eg. Orthro Evra, Nicoderm CQ)
  • Metal IUD (s)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Male Smokers	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 day. The nicotine solution (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/70 kg) will be administered first and the higher dose (2.0 mg/70kg) will be administered last.; Other Names: IV Nicotine; 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.
Active Comparator: Female Smokers (Follicular Phase)	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 day. The nicotine solution (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/70 kg) will be administered first and the higher dose (2.0 mg/70kg) will be administered last.; Other Names: IV Nicotine; 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.
Active Comparator: Female Smokers (Luteal Phase)	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 day. The nicotine solution (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/70 kg) will be administered first and the higher dose (2.0 mg/70kg) will be administered last.; Other Names: IV Nicotine; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of progesterone on IV nicotine, hormones and subjective ratings	We are examining the effects of progesterone on the acute effects of IV nicotine and BOLD signal active in areas of the brain with high levels of nicotine receptors. Correlational analyses between brain activation patterns, serum nicotine levels, serum/plasma hormone levels, and nicotine-induced changes in subjective statues, as measured by a visual analog scale, are being evaluated.	From baseline to study completion (approximately 8 months for males and 2 years for females)

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• 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: 2006-p-001985