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Nicotine Related Brain Activity: The Influence of Smoking History and Blood Nicotine Levels

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01588561
First Posted: May 1, 2012
Last Update Posted: August 31, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
Scott Lukas, Mclean Hospital
  Purpose
In this study, we sought to explore brain activity in nicotine-dependent men in response to acute intravenous nicotine using pharmacological magnetic resonance imaging (phMRI).

Condition Intervention
Nicotine Dependence Drug: Intravenous Nicotine Other: Saline - placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Other
Official Title: Nicotine Related Brain Activity: The Influence of Smoking History and Blood Nicotine Levels, an Exploratory Study

Resource links provided by NLM:


Further study details as provided by Scott Lukas, Mclean Hospital:

Primary Outcome Measures:
  • Peak Nicotine Levels [ Time Frame: 0, 2, 4, 6, 8, 10, 12, 14, 16, 20, 30 minutes post-infusion ]
    Peak nicotine level in each participant

  • Number of Brain Regions With a Change in Brain Activity Relative to Saline [ Time Frame: 40 minutes after infusion ]

    PhMRI analysis of the differential response of nicotine compared to the saline condition when analyzed with the nicotine time course.

    The main dependent variable in this study, Blood Oxygen Level Dependent (BOLD) measures of brain activity (via fMRI) data does not exist in a vacuum—it is always relative to another measure of brain activity, typically collected at rest or after a placebo injection. So we collected the data after the IV placebo injection alone and the IV nicotine injection alone, but then need applied mathematical CONTRASTS to the data. This procedure results in the brain activity maps.



Secondary Outcome Measures:
  • Number of Brain Regions With a Change in Brain Activity Relative to Saline When Analyzed With the Nicotine Time Course Controlling for Smoking History [ Time Frame: 40 minutes after infusion ]

    PhMRI analysis of the differential response of nicotine compared to the saline condition when analyzed with the nicotine time course controlling for smoking history (pack years).

    The main dependent variable in this study, Blood Oxygen Level Dependent (BOLD) measures of brain activity (via fMRI) data does not exist in a vacuum—it is always relative to another measure of brain activity, typically collected at rest or after a placebo injection. So we collected the data after the IV placebo injection alone and the IV nicotine injection alone, but then need applied mathematical CONTRASTS to the data. This procedure results in the brain activity maps.


  • Number of Brain Regions With a Change in Brain Activity Relative to Saline When Analyzed With Smoking History Controlling for Nicotine [ Time Frame: 40 minutes after infusion ]
    PhMRI analysis of the differential response of nicotine compared to the saline condition when analyzed with smoking history (pack years) controlling for nicotine. The main dependent variable in this study, Blood Oxygen Level Dependent (BOLD) measures of brain activity (via fMRI) data does not exist in a vacuum—it is always relative to another measure of brain activity, typically collected at rest or after a placebo injection. So we collected the data after the IV placebo injection alone and the IV nicotine injection alone, but then need applied mathematical CONTRASTS to the data. This procedure results in the brain activity maps.

  • Final Nicotine Levels [ Time Frame: 30 minutes post-infusion ]
    Final nicotine level in each participant


Enrollment: 15
Study Start Date: October 2005
Study Completion Date: September 2015
Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Intravenous Nicotine (1.5 mg/70 kg)
Participants are given a siingle infusion of nicotine (1.5 mg/70 kg), administered over 1 minute into the antecubital vein 10 minutes into their MRI scans
Drug: Intravenous Nicotine
Subjects received a single infusion of nicotine, 1.5 mg/70kg (New England Compounding Center, Framingham, MA), administered over 1 minute into the antecubital vein 10 minutes into their MRI scans.
Other Name: IV Nicotine
Placebo Comparator: Saline - placebo
Participants are given physiological saline, administered over 1 minute into the antecubital vein 10 minutes into their MRI scans
Other: Saline - placebo
Subjects received a single infusion of saline, administered over 1 minute into the antecubital vein 10 minutes into their MRI scans.

Detailed Description:
phMRI was used to evaluate brain activity in response to 1.5 mg/70 kg intravenous nicotine or saline. The nicotine and saline were administered on different visits. The time courses of individual subjects' nicotine levels were used as regressors to assess neural activity relating to the infusions. The influence of Smoking history and physiological measures on the response to nicotine were also investigated.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01588561


Locations
United States, Massachusetts
Alcohol and Drug Abuse Research Center at McLean Hospital
Belmont, Massachusetts, United States, 02478
Sponsors and Collaborators
Mclean Hospital
National Institute on Drug Abuse (NIDA)
Investigators
Principal Investigator: Scott E. Lukas, PhD Mclean Hospital
Principal Investigator: Harrison G Pope, MD Mclean Hospital
  More Information

Publications:
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 ( U.S. NIH Grant/Contract )
First Submitted: April 6, 2012
First Posted: May 1, 2012
Results First Submitted: November 29, 2016
Results First Posted: August 31, 2017
Last Update Posted: August 31, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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