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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Mclean Hospital
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Scott Lukas, Mclean Hospital
ClinicalTrials.gov Identifier:
NCT01588561
First received: April 6, 2012
Last updated: January 28, 2014
Last verified: January 2014
  Purpose

Clinical studies are proposed to measure the covariance between nicotine-induced changes in endocrine, subjective and cardiovascular effects and the temporal concordance with increases in serum nicotine and cotinine levels. Possible gender and menstrual cycle phase influences on the effects of nicotine on hypothalamic-pituitary-adrenal axis (HPA) and hypothalamic-pituitary-gonadal axis (HPG) hormones have not been clearly delineated. Accordingly, the investigators propose to compare the acute effects of nicotine in men and women, and to study women at the follicular and the luteal phases of the menstrual cycle.


Condition Intervention
Nicotine Dependence
Drug: Intravenous Nicotine

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Official Title: Effects of IV Nicotine Induced Changes on BOLD fMRI Signal, Hormones, and Subjective Ratings of Stimulant Drug Effect

Resource links provided by NLM:


Further study details as provided by Mclean Hospital:

Primary Outcome Measures:
  • Effects of Nicotine on BOLD fMRI Signal [ Time Frame: From baseline to study completion (approximately 4 months for males and 8 months for females) ] [ Designated as safety issue: No ]
    The investigators are examining the acute effects of IV nicotine on BOLD signal activation in areas of the brain with high levels of nicotine receptors.

  • Effects of Nicotine on the hypothalamic-pituitary-gonadal (HPG) axis [ Time Frame: From baseline to study completion (approximately 4 months for males and 8 months for females) ] [ Designated as safety issue: No ]
    The investigators are examining the effects of IV nicotine on serum nicotine levels and serum/plasma HPG hormone levels.

  • Effects of Nicotine on hypothalamic-pituitary-adrenal axis (HPA) hormones [ Time Frame: From baseline to study completion (approximately 4 months for males and 8 months for females) ] [ Designated as safety issue: No ]
    The investigators are examining the effects of IV nicotine on serum nicotine levels and serum/plasma hormone levels.


Secondary Outcome Measures:
  • Effects of Nicotine on Mood States on the Visual Analog Scale [ Time Frame: From baseline to study completion (approximately 4 months for males and 8 months for females) ] [ Designated as safety issue: No ]
    The investigators are examining the effects of IV nicotine on nicotine-induced changes in subjective states, as measured by a visual analog scale.

  • Effects of Nicotine on Cardiovascular Measures [ Time Frame: From baseline to study completion (approximately 4 months for males and 8 months for females) ] [ Designated as safety issue: No ]
    The investigators are examining the effects of IV Nicotine induced changes and cardiovascular measures, as measured by blood pressure and heart rate.


Estimated Enrollment: 200
Study Start Date: October 2005
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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/70 kg or 1.5 mg/70 kg or 2.0mg/70 kg;) 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 IV nicotine over 10 seconds without any adverse reactions. The investigators concur with the IRB recommendation that the lower doses (1.0mg/70 kg and 1.5 mg/70 kg) should be administered first and the higher dose (2.0mg/70 kg ) will be administered last.
Other Name: IV Nicotine
Active Comparator: Female Smokers (Mid-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/70 kg or 1.5 mg/70 kg or 2.0mg/70 kg;) 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 IV nicotine over 10 seconds without any adverse reactions. The investigators concur with the IRB recommendation that the lower doses (1.0mg/70 kg and 1.5 mg/70 kg) should be administered first and the higher dose (2.0mg/70 kg ) will be administered last.
Other Name: IV Nicotine
Active Comparator: Female Smokers (Early Follicular Phase; cycle days 4-8) 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/70 kg or 1.5 mg/70 kg or 2.0mg/70 kg;) 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 IV nicotine over 10 seconds without any adverse reactions. The investigators concur with the IRB recommendation that the lower doses (1.0mg/70 kg and 1.5 mg/70 kg) should be administered first and the higher dose (2.0mg/70 kg ) will be administered last.
Other Name: IV Nicotine

Detailed Description:

This clinical study will analyze the interactions between nicotine, endocrine hormone alterations, mood, cardiovascular measures, and patterns of brain activation to determine if they are affected by gender and menstrual cycle phase. These studies will advance our understanding of the neurobiology of nicotine's behavioral effects, and could be important in developing novel treatments for smoking cessation. Cigarette smoking remains a leading cause of death and disease and the proposed studies will advance knowledge of the ways in which gender and menstrual cycle phase may influence patterns of brain activation induced by nicotine and consequently the development and maintenance of nicotine dependence.

  Eligibility

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

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 18.0 and 27.0 for women and 21.4 to 29 for men.
  • 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 and men with a BMI outside the range 21.4-29.0.
  • 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)
  • Participants who describe themselves as seeking treatment will not be selected but will be referred to local smoking cessation programs.
  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: NCT01588561

Contacts
Contact: Andrew R Kerrigan, BA 617-855-2746 AKerrigan@mclean.harvard.edu

Locations
United States, Massachusetts
Alcohol and Drug Abuse Research Center at McLean Hospital Recruiting
Belmont, Massachusetts, United States, 02478
Contact: Scott E. Lukas, PhD    617-855-2767    lukas@mclean.harvard.edu   
Contact: Harrison G Pope, MD    617-855-2911    hpope@mclean.harvard.edu   
Principal Investigator: Scott E. Lukas, PhD         
Sub-Investigator: Arthur J Siegel, MD         
Sub-Investigator: Michael Rohan, PhD         
Sub-Investigator: David Olson, MD, PhD         
Sub-Investigator: Rinah Yamamoto, PhD         
Principal Investigator: Harrison G Pope, MD         
Sponsors and Collaborators
Mclean Hospital
Investigators
Principal Investigator: Scott E. Lukas, PhD Mclean Hospital
Principal Investigator: Harrison G Pope, MD Mclean Hospital
  More Information

No publications provided

Responsible Party: Scott Lukas, Director, McLean Imaging Center, Mclean Hospital
ClinicalTrials.gov Identifier: NCT01588561     History of Changes
Other Study ID Numbers: 2005-p-001656, R01DA025065
Study First Received: April 6, 2012
Last Updated: January 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Tobacco Use Disorder
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Central Nervous System Stimulants
Nicotine
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 11, 2014