Cigarette SmokingNMRNCT01627392
Mechanisms of the Nicotine Metabolism Effect on Tobacco Dependence
A study testing Smoking abstinence in people with Cigarette Smoking, run by University of California, San Francisco at 1 site in United States.
Trial summary
The purpose of the study is to learn more about tobacco dependence and nicotine metabolism in African-Americans and whites, by studying to see if how fast a person metabolizes nicotine (how the body breaks down nicotine into inactive compounds) affects how dependent they are on smoking cigarettes. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Cigarette Smoking
- What is being tested?
- Smoking abstinence
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 305 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2012to Aug 2015
- Phase
- Interventional
- 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 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- African-American or Caucasian
- Age 18-70 years
- Regular smoker of 5 or more cigarettes per day
- Saliva cotinine of 100 ng/ml or greater
Who cannot join
- Obese (BMI > 38) or underweight (BMI < 17)
- Major systemic or psychiatric condition
- Medications that are inducers of CYP2A6
- History of alcohol abuse
- Positive drug urine tox test
- Pregnancy or breast feeding
Trial locations and contacts
1 site in 1 country.
United States1 site
San Francisco General Hospital
San Francisco, California, 94110
About this study
The purpose of the study is to learn more about tobacco dependence and nicotine metabolism in African-Americans and whites, by studying to see if how fast a person metabolizes nicotine (how the body breaks down nicotine into inactive compounds) affects how dependent they are on smoking cigarettes. The investigators believe that people with a faster rate of metabolism may have more severe nicotine withdrawal symptoms and also may have a harder time trying to quit smoking.
Read the detailed description
Our studies will use the nicotine metabolite ratio (NMR) (the ratio between the nicotine metabolites 3'hydroxycotinine and cotinine)as a simple and clinically feasible biomarker for the rate of nicotine metabolism. The investigators hypothesize that a faster rate of metabolism leads to faster elimination of nicotine from the body and a more rapid dissipation of brain tolerance to nicotine in the interval between cigarettes, leading in turn to (1) more severe nicotine withdrawal symptoms and (2) greater subjective reward from the cigarette smoked following deprivation. These effects would help to explain why smokers with faster rates of nicotine metabolism have a poorer response to smoking cessation therapy when compared to those with slower rates of metabolism.
The investigators will explore the relationship of the NMR to the endophenotypes of withdrawal, craving and reward, with the assumption that these factors are likely intermediaries for the mechanism linking nicotine metabolism to tobacco dependence and smoking cessation rates with pharmacotherapy. Our study design uses a brief (6 hour) interval of smoking abstinence followed by a "reward" cigarette to elicit the subjective responses relating to withdrawal and reward. Because smoking behavior and severity of nicotine dependence vary by race and sex the investigators will also compare the relationship between NMR and withdrawal and reward in African American vs white smokers and in men vs women.
Secondary analyses will examine whether nicotine half-life mediates the observed effects of NMR on primary response measures.
- Conditions
- Cigarette Smoking
- Being tested
- Smoking abstinence
- Medical subject headings
- Cigarette Smoking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Smoking abstinenceBehavioural
6 hour smoking abstinence
| Study group | Role | What they receive |
|---|---|---|
| Smoking abstinence | Experimental | Not described Receives: Behavioral: Smoking abstinence |
What is being measured
The primary outcome is the main question the study is designed to answer.
Nicotine withdrawal symptoms
Total withdrawal score as measured by Minnesota Nicotine Withdrawal Scale
Measured: 6 hours post nicotine load
Secondary outcomes (4)
Cognitive performance
Cognitive performance will be measured by n-back computerized testing
Measured: 6 hours post nicotine load
Smoking behavior: number of cigarettes
Smoking behavior will be measured by number of cigarettes during a monitoring period following the 3rd (reward) cigarette of the protocol
Measured: 90 minutes post-abstinence
Smoking behavior: number of puffs per cigarette
Smoking behavior will be measured by number of puffs per cigarette during a monitoring period following the 3rd (reward) cigarette of the protocol
Measured: 90 minutes post-abstinence
Smoking behavior: time to first post-reward cigarette
Smoking behavior will be measured by time to first post-reward cigarette during a monitoring period following the 3rd (reward) cigarette of the protocol
Measured: 90 minutes post-abstinence
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2012 (estimated)
- Study startJul 2012
- Primary completionAug 2015
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cigarette SmokingStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 305 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Neal L Benowitz, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01627392
- Sponsor's protocol ID
- 12-08635
- Acronym
- NMR
- Status last verified
- Dec 2015
- First submitted
- 14 Jun 2012
- Last updated
- 3 Dec 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Nardone N, Shahid M, Strasser AA, Dempsey DA, Benowitz NL. The influence of nicotine metabolic rate on working memory over 6 hours of abstinence from nicotine. Pharmacol Biochem Behav. 2020 Jan;188:172836. doi: 10.1016/j.pbb.2019.172836. Epub 2019 Dec 5.
PubMed 31812759Liakoni E, Edwards KC, St Helen G, Nardone N, Dempsey DA, Tyndale RF, Benowitz NL. Effects of Nicotine Metabolic Rate on Withdrawal Symptoms and Response to Cigarette Smoking After Abstinence. Clin Pharmacol Ther. 2019 Mar;105(3):641-651. doi: 10.1002/cpt.1238. Epub 2018 Oct 25.
PubMed 30242831
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms of the Nicotine Metabolism Effect on Tobacco Dependence
- ClinicalTrials.gov ID
- NCT01627392
- Acronym / sponsor ID
- NMR / 12-08635
- Conditions
- Cigarette Smoking
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 305 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Study start
- Jul 2012
- Primary completion
- Aug 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 25 Jun 2012 (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 purpose of the study is to learn more about tobacco dependence and nicotine metabolism in African-Americans and whites, by studying to see if how fast a person metabolizes nicotine (how the body breaks down nicotine into inactive compounds) affects how dependent they are on smoking cigarettes. The investigators believe that people with a faster rate of metabolism may have more severe nicotine withdrawal symptoms and also may have a harder time trying to quit smoking.
Detailed description
Our studies will use the nicotine metabolite ratio (NMR) (the ratio between the nicotine metabolites 3'hydroxycotinine and cotinine)as a simple and clinically feasible biomarker for the rate of nicotine metabolism. The investigators hypothesize that a faster rate of metabolism leads to faster elimination of nicotine from the body and a more rapid dissipation of brain tolerance to nicotine in the interval between cigarettes, leading in turn to (1) more severe nicotine withdrawal symptoms and (2) greater subjective reward from the cigarette smoked following deprivation. These effects would help to explain why smokers with faster rates of nicotine metabolism have a poorer response to smoking cessation therapy when compared to those with slower rates of metabolism.
The investigators will explore the relationship of the NMR to the endophenotypes of withdrawal, craving and reward, with the assumption that these factors are likely intermediaries for the mechanism linking nicotine metabolism to tobacco dependence and smoking cessation rates with pharmacotherapy. Our study design uses a brief (6 hour) interval of smoking abstinence followed by a "reward" cigarette to elicit the subjective responses relating to withdrawal and reward. Because smoking behavior and severity of nicotine dependence vary by race and sex the investigators will also compare the relationship between NMR and withdrawal and reward in African American vs white smokers and in men vs women.
Secondary analyses will examine whether nicotine half-life mediates the observed effects of NMR on primary response measures.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Smoking abstinence | Experimental | Behavioral: Smoking abstinence |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- African-American or Caucasian
- Age 18-70 years
- Regular smoker of 5 or more cigarettes per day
- Saliva cotinine of 100 ng/ml or greater
Key exclusion criteria (6 listed)
- Obese (BMI > 38) or underweight (BMI < 17)
- Major systemic or psychiatric condition
- Medications that are inducers of CYP2A6
- History of alcohol abuse
- Positive drug urine tox test
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Smoking abstinence6 hour smoking abstinence | Behavioural | Smoking abstinence |
Primary outcome
Nicotine withdrawal symptoms
Time frame: 6 hours post nicotine load
Total withdrawal score as measured by Minnesota Nicotine Withdrawal Scale
4 secondary outcomes
Cognitive performance
Time frame: 6 hours post nicotine load
Smoking behavior: number of cigarettes
Time frame: 90 minutes post-abstinence
Smoking behavior: number of puffs per cigarette
Time frame: 90 minutes post-abstinence
Smoking behavior: time to first post-reward cigarette
Time frame: 90 minutes post-abstinence
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 3 Dec 2015.
- Derived from this study: PubMed 31812759Nardone N, Shahid M, Strasser AA, Dempsey DA, Benowitz NL. The influence of nicotine metabolic rate on working memory over 6 hours of abstinence from nicotine. Pharmacol Biochem Behav. 2020 Jan;188:172836. doi: 10.1016/j.pbb.2019.172836. Epub 2019 Dec 5.
- Derived from this study: PubMed 30242831Liakoni E, Edwards KC, St Helen G, Nardone N, Dempsey DA, Tyndale RF, Benowitz NL. Effects of Nicotine Metabolic Rate on Withdrawal Symptoms and Response to Cigarette Smoking After Abstinence. Clin Pharmacol Ther. 2019 Mar;105(3):641-651. doi: 10.1002/cpt.1238. Epub 2018 Oct 25.
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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.
Neal L Benowitz, MD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Smoking abstinence in people with Cigarette Smoking, run by University of California, San Francisco 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 4 inclusion and 6 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 3 Dec 2015. 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?
Nicotine withdrawal symptoms (time frame: 6 hours post nicotine load). 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 NCT01627392, which also lists 2 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 3 Dec 2015.