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Completed

NCT Number: NCT01588561

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

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).

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Key information

Age range

18 year–40 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Alcohol and Drug Abuse Research Center at McLean Hospital

Belmont, Massachusetts, 02478, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Intravenous Nicotine

Drug

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 names: IV Nicotine

Saline - placebo

Other

Subjects received a single infusion of saline, administered over 1 minute into the antecubital vein 10 minutes into their MRI scans.

Primary outcomes

  1. 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

  2. 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 outcomes

  1. 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.

  2. 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.

  3. Final Nicotine Levels

    Time frame: 30 minutes post-infusion

    Final nicotine level in each participant

Sponsors and collaborators

Lead sponsor

Mclean Hospital

Other

Collaborators

  • National Institute on Drug Abuse (NIDA)

Registry information

Official study title

Nicotine Related Brain Activity: The Influence of Smoking History and Blood Nicotine Levels, an Exploratory Study

Important dates

Study start
2005
Primary completion
2015
Study completion
2015
First posted
May 1, 2012
Registry last updated
Aug 31, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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