search
Back to results

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

Primary Purpose

Nicotine Dependence

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Intravenous Nicotine
Saline - placebo
Sponsored by
Mclean Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Nicotine Dependence

Eligibility Criteria

18 Years - 40 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Alcohol and Drug Abuse Research Center at McLean Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Intravenous Nicotine (1.5 mg/70 kg)

Saline - placebo

Arm Description

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

Participants are given physiological saline, administered over 1 minute into the antecubital vein 10 minutes into their MRI scans

Outcomes

Primary Outcome Measures

Peak Nicotine Levels
Peak nicotine level in each participant
Number of Brain Regions With a Change in Brain Activity Relative to Saline
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
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
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
Final nicotine level in each participant

Full Information

First Posted
April 6, 2012
Last Updated
July 31, 2017
Sponsor
Mclean Hospital
Collaborators
National Institute on Drug Abuse (NIDA)
search

1. Study Identification

Unique Protocol Identification Number
NCT01588561
Brief Title
Nicotine Related Brain Activity: The Influence of Smoking History and Blood Nicotine Levels
Official Title
Nicotine Related Brain Activity: The Influence of Smoking History and Blood Nicotine Levels, an Exploratory Study
Study Type
Interventional

2. Study Status

Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
October 2005 (undefined)
Primary Completion Date
July 2015 (Actual)
Study Completion Date
September 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mclean Hospital
Collaborators
National Institute on Drug Abuse (NIDA)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nicotine Dependence

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Intravenous Nicotine (1.5 mg/70 kg)
Arm Type
Active Comparator
Arm Description
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
Arm Title
Saline - placebo
Arm Type
Placebo Comparator
Arm Description
Participants are given physiological saline, administered over 1 minute into the antecubital vein 10 minutes into their MRI scans
Intervention Type
Drug
Intervention Name(s)
Intravenous Nicotine
Other Intervention Name(s)
IV Nicotine
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Saline - placebo
Intervention Description
Subjects received a single infusion of saline, administered over 1 minute into the antecubital vein 10 minutes into their MRI scans.
Primary Outcome Measure Information:
Title
Peak Nicotine Levels
Description
Peak nicotine level in each participant
Time Frame
0, 2, 4, 6, 8, 10, 12, 14, 16, 20, 30 minutes post-infusion
Title
Number of Brain Regions With a Change in Brain Activity Relative to Saline
Description
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.
Time Frame
40 minutes after infusion
Secondary Outcome Measure Information:
Title
Number of Brain Regions With a Change in Brain Activity Relative to Saline When Analyzed With the Nicotine Time Course Controlling for Smoking History
Description
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.
Time Frame
40 minutes after infusion
Title
Number of Brain Regions With a Change in Brain Activity Relative to Saline When Analyzed With Smoking History Controlling for Nicotine
Description
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.
Time Frame
40 minutes after infusion
Title
Final Nicotine Levels
Description
Final nicotine level in each participant
Time Frame
30 minutes post-infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Scott E. Lukas, PhD
Organizational Affiliation
Mclean Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Harrison G Pope, MD
Organizational Affiliation
Mclean Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Alcohol and Drug Abuse Research Center at McLean Hospital
City
Belmont
State/Province
Massachusetts
ZIP/Postal Code
02478
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
23117126
Citation
Yamamoto RT, Rohan ML, Goletiani N, Olson D, Peltier M, Renshaw PF, Mello NK. Nicotine related brain activity: the influence of smoking history and blood nicotine levels, an exploratory study. Drug Alcohol Depend. 2013 Apr 1;129(1-2):137-44. doi: 10.1016/j.drugalcdep.2012.10.002. Epub 2012 Oct 29.
Results Reference
result

Learn more about this trial

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

We'll reach out to this number within 24 hrs