Nicotine and Brain Imaging Research Study

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University of Pennsylvania
Sponsor:
Information provided by (Responsible Party):
C. Neill Epperson, University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT01227343
First received: October 22, 2010
Last updated: June 24, 2014
Last verified: June 2014
  Purpose

The aim of this study is to assess the impact of smoking on cortical GABA levels in males and females. Using magnetic resonance spectroscopy (MRS), we will examine the impact of sex and menstrual cycle phase on brain neurochemistry in healthy smokers and non-smokers. We hypothesize that female, but not male, smokers will have reduced cortical GABA levels compared to their non-smoking, sex-matched counterparts.


Condition
Nicotine

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Sex, GABA and Nicotine: A 1H-MRS Study

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • To estimate and compare the impact of smoking on cortical GABA levels in male and female smokers and non-smokers. [ Time Frame: 3-10 weeks ] [ Designated as safety issue: No ]
    Preliminary findings suggest that nicotine's effects on cortical GABA levels vary by sex with women experiencing the greatest smoking-induced alterations in cortical GABA levels. We hypothesize that female, but not male, smokers will have reduced cortical GABA levels compared to their non-smoking, sex-matched counterparts.


Secondary Outcome Measures:
  • To measure occipital cortex GABA concentrations in healthy female smokers across the menstrual cycle and to compare their GABA levels with those from a healthy female non-smoking control group. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • To determine the impact of 10-14 days of smoking abstinence on cortical GABA concentrations in female smokers. [ Time Frame: 10-14 days ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples Without DNA

Whole blood, plasma, urine


Estimated Enrollment: 54
Study Start Date: March 2010
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
Female Smokers
Healthy females who smoke 10-30 cigarettes per day for the past 2 years and meet criteria for nicotine dependence.
Female Non-smokers
Healthy females who do not currently smoke cigarettes.
Male Smokers
Healthy males who smoke 10-30 cigarettes per day for the past 2 years and who meet criteria for nicotine dependence.
Male - Non-Smokers CLOSED
WE ARE NO LONGER RECRUITING MALE NON-SMOKERS

Detailed Description:

The purpose of this study is to measure and compare gamma-aminobutyric acid (GABA) levels in the occipital cortex of a group of healthy smoking and non-smoking women and men ages 18-50. We will recruit women with regular menstrual cycles so that we can assess premenstrual impact of smoking cessation in that population and compare GABA level concentrations across all groups. Although there are several note-worthy differences between male and females in regard to smoking behavior, ultimately none are as worrisome as the disparity in ability to quit smoking. While multiple explanations for why women are less successful in their abstinence attempts have been proffered, the observation that women are more likely to experience emergence of depressive symptoms during smoking cessation, a known risk factor for relapse, may be the most important contributor to this sex-specific recidivism. Several lines of evidence suggest that nicotine modulation of GABA may play an important role in this interplay between sex, depression, and smoking recidivism.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Women and men from the greater Philadelphia and surrounding areas who are ages 18-50 will be considered for enrollment into this study.

Criteria

Inclusion Criteria:

Women ages 18-50 will be eligible for this study if they:

  • Meet DSM-IV criteria for nicotine dependence for at least the past 2 years;
  • Smoke 10-30 cigarettes per day for the past two years;
  • Have clear urine toxicology screen upon recruitment and a plasma cotinine level of > 210 ng/ml;
  • Have an expired CO (carbon monoxide) level of > 11ppm;
  • Have regular menstrual cycles 24 to 36 days in length;
  • Do not have an elevated follicular stimulating hormone (FSH) >20 (>20 is potentially indicative of menopause and would be an exclusion criterion);
  • Have no history of major depressive disorder, generalized anxiety disorder, and or panic disorder within the last three years according to the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-NP) (First et al., 1995); a history of major depressive disorder, generalized anxiety disorder, and or panic disorder greater than 3 years ago, but now resolved according to the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-NP) (First et al., 1995), is allowed;
  • Have no substance abuse disorders (this includes alcohol, prescription, and illicit substances) within the last three years other than nicotine dependence according to the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-NP) (First et al., 1995);
  • Subject has history of substance abuse disorders (this includes alcohol, prescription, and illicit substances) >3 years ago but the period of abuse did not last more than 5 years according to the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-NP) (First et al., 1995);
  • No history of clinically interfering premenstrual mood changes;
  • Are able to give written informed consent;
  • Are fluent in written and spoken English.

Exclusion Criteria:

  • A psychiatric history of psychotic disorders, bipolar disorder, obsessive compulsive disorder, eating disorders, post-traumatic stress disorder, phobias (includes simple and specific phobias) and Axis II disorders;
  • A history of serious medical or neurological illness, including (but not limited to) major cardiovascular disease, severe hypertension, intracranial mass lesions, seizure disorder, severe hepatic or renal disease, unstable endocrine or metabolic disease, and unstable hematologic disease;
  • Use of psychotropic medication within the previous 12 months;
  • Hazardous drinking in the previous 90 days defined as more than 7 drinks per week for women and more than 14 drinks per week for men, or more than 3 and 4 drinks in a single day for women and men, respectively;
  • Hamilton Rating Scale for Depression (HAM-D; Hamilton, 1960) score >12;
  • Mini-Mental State Examination (MMSE) >24;
  • Use of steroidal contraceptives or hormone treatment within the previous 4 months;
  • Current pregnancy;
  • History of claustrophobic symptoms;
  • Metallic implants.

For Healthy Non-Smoking Females:

Same inclusion/exclusion criteria for smoking females with the exception of the criteria related to smoking.

For Smoking Males:

Same inclusion/exclusion criteria for smoking females with the exception of the criteria related to menstrual cycle, conception, and FSH.

For Healthy Non-Smoking Males:

Same inclusion/exclusion criteria for smoking males with the exception of the criteria related to smoking.

  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: NCT01227343

Contacts
Contact: Claudia Schinstine, M.A. 215-417-8839 sclaud@mail.med.upenn.edu

Locations
United States, Pennsylvania
Penn Center for Women's Behavioral Wellness, University of Pennsylvania School of Medicine Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Claudia Schinstine, M.A.    215-417-8839    sclaud@upenn.edu   
Principal Investigator: C. Neill Epperson, M.D.         
Sponsors and Collaborators
University of Pennsylvania
Investigators
Principal Investigator: C. Neill Epperson, M.D. University of Pennsylvania
  More Information

Additional Information:
Publications:
Responsible Party: C. Neill Epperson, Associate Professor of Psychiatry, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT01227343     History of Changes
Other Study ID Numbers: 810278
Study First Received: October 22, 2010
Last Updated: June 24, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Pennsylvania:
Gender differences
nicotine
cigarette smoking habits
behavior changes

Additional relevant MeSH terms:
Nicotine
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 29, 2014