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

NCT01588561 | Completed Results DMC

• 2 other identifiers: 2005-p-001656R01DA025065
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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).

Conditions

Nicotine Dependence

Outcome Measures

Primary Outcomes (2)

• Peak Nicotine Levels

  Peak nicotine level in each participant

  0, 2, 4, 6, 8, 10, 12, 14, 16, 20, 30 minutes post-infusion

• 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.

  40 minutes after infusion

Secondary Outcomes (3)

• Number of Brain Regions With a Change in Brain Activity Relative to Saline When Analyzed With the Nicotine Time Course Controlling for Smoking History

  40 minutes after infusion

• Number of Brain Regions With a Change in Brain Activity Relative to Saline When Analyzed With Smoking History Controlling for Nicotine

  40 minutes after infusion

• Final Nicotine Levels

  30 minutes post-infusion

Study Arms (2)

Intravenous Nicotine (1.5 mg/70 kg)

ACTIVE COMPARATOR

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

Saline - placebo

PLACEBO COMPARATOR

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

Other: Saline - placebo

Interventions

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.

Also known as: IV Nicotine

Intravenous Nicotine (1.5 mg/70 kg)

Saline - placebo OTHER

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

Saline - placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Mclean Hospital: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Alcohol and Drug Abuse Research Center at McLean Hospital

Belmont, Massachusetts, 02478, United States

Location

Related Publications (1)

• 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.

  PMID: 23117126 RESULT

MeSH Terms

Conditions

Tobacco Use Disorder

Interventions

Nicotine

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

Small number of subjects completed due to a large shortage of Nicotine Bitartrate (the chemical used to create our IV Nicotine). We were unable to receive new nicotine shipments from 4/14 -2/15.Without this nicotine it was impossible to run subjects.

Results Point of Contact

• Title: Scott Lukas, Ph.D.
• Organization: McLean Hospital

slukas@mclean.harvard.edu

617-855-2767

Study Officials

• Scott E. Lukas, PhD

  Mclean Hospital

  PRINCIPAL INVESTIGATOR

• Harrison G Pope, MD

  Mclean Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, McLean Imaging Center

Study Record Dates

• First Submitted: April 6, 2012
• First Posted: May 1, 2012
• Study Start: October 1, 2005
• Primary Completion: July 1, 2015
• Study Completion: September 1, 2015
• Last Updated: August 31, 2017
• Results First Posted: August 31, 2017

Record last verified: 2017-07

Locations

US (1)