NicotineNCT01227343
Nicotine and Brain Imaging Research Study
An observational study of Nicotine, run by University of Pennsylvania at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Nicotine
- How many people
- 54 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2010to Nov 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
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.
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Penn Center for Women's Behavioral Wellness, University of Pennsylvania School of Medicine
Philadelphia, Pennsylvania, 19104
About this study
Official title: Sex, GABA and Nicotine: A 1H-MRS Study
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.
Read the 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.
- Conditions
- Nicotine
- Keywords
- Gender differences, nicotine, cigarette smoking habits, behavior changes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To estimate and compare the impact of smoking on cortical GABA levels in male and female smokers and non-smokers.
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.
Measured: 3-10 weeks
Secondary outcomes (2)
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.
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.
Measured: 8 weeks
To determine the impact of 10-14 days of smoking abstinence on cortical GABA concentrations in female smokers.
To determine the impact of 10-14 days of smoking abstinence on cortical GABA concentrations in female smokers.
Measured: 10-14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2010 (estimated)
- Study startMar 2010
- Primary completionNov 2016
- Study completionNov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for NicotineStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Cynthia N Epperson, M.D., Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01227343
- Sponsor's protocol ID
- 810278
- Status last verified
- Aug 2021
- First submitted
- 22 Oct 2010
- Last updated
- 4 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
Publications
Epperson CN, Haga K, Mason GF, Sellers E, Gueorguieva R, Zhang W, Weiss E, Rothman DL, Krystal JH. Cortical gamma-aminobutyric acid levels across the menstrual cycle in healthy women and those with premenstrual dysphoric disorder: a proton magnetic resonance spectroscopy study. Arch Gen Psychiatry. 2002 Sep;59(9):851-8. doi: 10.1001/archpsyc.59.9.851.
PubMed 12215085Epperson CN, O'Malley S, Czarkowski KA, Gueorguieva R, Jatlow P, Sanacora G, Rothman DL, Krystal JH, Mason GF. Sex, GABA, and nicotine: the impact of smoking on cortical GABA levels across the menstrual cycle as measured with proton magnetic resonance spectroscopy. Biol Psychiatry. 2005 Jan 1;57(1):44-8. doi: 10.1016/j.biopsych.2004.09.021.
PubMed 15607299Epperson CN, Toll B, Wu R, Amin Z, Czarkowski KA, Jatlow P, Mazure CM, O'Malley SS. Exploring the impact of gender and reproductive status on outcomes in a randomized clinical trial of naltrexone augmentation of nicotine patch. Drug Alcohol Depend. 2010 Nov 1;112(1-2):1-8. doi: 10.1016/j.drugalcdep.2010.04.021. Epub 2010 Jun 19.
PubMed 20561758
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sex, GABA and Nicotine: A 1H-MRS Study
- ClinicalTrials.gov ID
- NCT01227343
- Acronym / sponsor ID
- 810278
- Conditions
- Nicotine
- Keywords
- Gender differences, nicotine, cigarette smoking habits, behavior changes
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- Mar 2010 (actual)
- Primary completion
- Nov 2016 (actual)
- Study completion
- Nov 2017 (actual)
- First posted
- 25 Oct 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- 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.
Key inclusion criteria (13 listed)
- 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;
Key exclusion criteria (16 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
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.
2 secondary outcomes
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
To determine the impact of 10-14 days of smoking abstinence on cortical GABA concentrations in female smokers.
Time frame: 10-14 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2021.
- Background: PubMed 12215085Epperson CN, Haga K, Mason GF, Sellers E, Gueorguieva R, Zhang W, Weiss E, Rothman DL, Krystal JH. Cortical gamma-aminobutyric acid levels across the menstrual cycle in healthy women and those with premenstrual dysphoric disorder: a proton magnetic resonance spectroscopy study. Arch Gen Psychiatry. 2002 Sep;59(9):851-8. doi: 10.1001/archpsyc.59.9.851.
- Background: PubMed 15607299Epperson CN, O'Malley S, Czarkowski KA, Gueorguieva R, Jatlow P, Sanacora G, Rothman DL, Krystal JH, Mason GF. Sex, GABA, and nicotine: the impact of smoking on cortical GABA levels across the menstrual cycle as measured with proton magnetic resonance spectroscopy. Biol Psychiatry. 2005 Jan 1;57(1):44-8. doi: 10.1016/j.biopsych.2004.09.021.
- Background: PubMed 20561758Epperson CN, Toll B, Wu R, Amin Z, Czarkowski KA, Jatlow P, Mazure CM, O'Malley SS. Exploring the impact of gender and reproductive status on outcomes in a randomized clinical trial of naltrexone augmentation of nicotine patch. Drug Alcohol Depend. 2010 Nov 1;112(1-2):1-8. doi: 10.1016/j.drugalcdep.2010.04.021. Epub 2010 Jun 19.
- Program WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cynthia N Epperson, M.D. principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Nicotine, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01227343, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2021.