Substance-related DiscorderPhase 1NCT00618631
Effects of Smoking on Opioid Receptor Binding: A PET Study
A Phase 1 study testing Nicotine and Carfentanil in people with Substance-related Discorder, run by National Institute on Drug Abuse (NIDA) at 2 sites in United States.
Trial summary
Background: Tobacco smoking is one of the most preventable causes of morbidity and mortality in the world, but the addictive property of nicotine is such that fewer than 10 percent of people who attempt to quit smoking remain tobacco-free after 1 year. Read more about this study
- Who is it for?
- Ages 21 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Substance-related Discorder
- What is being tested?
- Nicotine and Carfentanil
- How many people
- 26 participants
- Where
- 2 sitesUnited States
- Study dates
- 17 Jan 2008to 8 Jan 2015
- Phase
- Phase 1
- 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 21 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 21-50 year old males and females
- smoke 10 cigarettes per day on average for at least 2 years
- urine cotinine level greater than or equal to 200 ng/ml (NicAlert reading greater than or equal to 4)
- estimated IQ score greater than or equal to 85 (competent to give informed consent)
- medically and psychologically healthy as determined by screening criteria.
- 21-50 year old males and females
Show all 10Show fewer
- smoked 1-20 cigarettes in their life and none in past year
- urine cotinine level less than 30 ng/ml (NicAlert reading less than or equal to 1)
- estimated IQ score greater than or equal to 85 (competent to give informed consent)
- medically and psychologically healthy as determined by screening criteria.
Who cannot join
- interest in reducing or quitting tobacco use
- treatment for nicotine dependence in the past 3 months
- current drug or alcohol abuse or dependence
- consumption of more than 15 alcoholic drinks per week during the past month
- any opiate use in the past 6 months
- marijuana use greater than one time per week on an average during the past month
Show all 39Show fewer
- other drug use greater than 2 time per month on average during the past 3 months.
- current use of any medication that would interfere with the protocol
- under the influence of a drug or alcohol at experimental sessions
- HIV positive
- history of psychotropic medications
- history of head injury with unconscious longer than 5 minutes
- implantable device or foreign body that would make an MRI examination unobtainable
- MRI abnormality judged clinically significant by the PI
- use of any investigational medication or device within the previous 30 days
- donation at least 450 ml of blood or equivalent levels of plasma within the previous 30 days
- exposure to ionizing radiation that, in combination with the study tracer, would result in a cumulative exposure exceeding 5 rem in one calendar year
- any subject judged by the PI to be inappropriate for the study.
- chronic pulmonary disease, including COPD, bronchitis, asthma, and emphysema
- pregnant, nursing, or become pregnant during the study
- use of any tobacco products in the past year
- current drug or alcohol abuse or dependence
- consumption of more than 15 alcoholic drinks per week during the past month
- any opiate use in the past 6 months
- marijuana use greater than one time per week on average during past month
- other drug use greater than two times per month on average during past three months.
- current use of any medication that would interfere with the protocol
- under the influence of a drug or alcohol at experimental sessions
- HIV positive
- history of psychotropic medications
- history of head injury with unconscious longer than 5 minutes
- implantable device or foreign body that would make an MRI examination unobtainable
- MRI abnormality judged clinically significant by the PI
- use of any investigational medication or device within the previous 30 days
- donation of at least 450 ml of blood or equivalent levels of plasma within the previous 30 days
- exposure to ionizing radiation that, in combination with the study tracer, would result in a cumulative exposure exceeding 5 rem in one calendar year
- any subject judged by the PI to be inappropriate for the study.
- chronic pulmonary disease, including COPD, bronchitis, asthma, and emphysema
- pregnant, nursing, or become pregnant during the study
Trial locations and contacts
2 sites in 1 country.
United States2 sites
National Institute on Drug Abuse
Baltimore, Maryland, 21224
Johns Hopkins Medical Institute
Baltimore, Maryland, 21287
About this study
Official title: Effects of Smoking on Opioid Receptor Binding Using [(11)C]Carfentanil: An Imaging PET Study
Background:
- Tobacco smoking is one of the most preventable causes of morbidity and mortality in the world, but the addictive property of nicotine is such that fewer than 10 percent of people who attempt to quit smoking remain tobacco-free after 1 year. Researchers are studying the addictive properties of nicotine in an attempt to develop more successful medication therapies for smoking cessation.
- Nicotine acts on chemical receptors in the brain, including opioid receptors that affect the perception of pain. Repeated nicotine administration can cause adaptations in the brain s opioid receptors, which heightens the addictive properties of nicotine and increases the likelihood and severity of withdrawal symptoms associated with smoking cessation. Researchers are interested in using positron emission tomography (PET) scanning to study brain chemical responses to nicotine in current smokers and nonsmokers.
Read more
Objectives:
- To study brain chemical activity related to cigarette smoking and nicotine administration.
- To compare the brain chemical activity of current daily smokers with that of nonsmokers.
Eligibility:
- Individuals 21 to 50 years of age who are either current smokers (10 to 25 cigarettes daily for at least 2 years) or have had some exposure to tobacco but have never smoked regularly (may have had a maximum of 20 cigarettes in their lifetime and none in past year).
Design:
- Eligible participants will undergo initial medical and psychological screening and neuropsychological testing before beginning the main phase of the study. Participants will be required to abstain from alcohol and drugs (except caffeine, nicotine, and prescription drugs) for 24 hours before each session, and smokers will refrain from smoking after midnight on the night before each session.
- Session 1: Participants will answer questions about nicotine craving and withdrawal symptoms, followed by a magnetic resonance imaging (MRI) scan to provide baseline information about brain activity.
- Session 2 and 3: Participants will answer questions about nicotine craving and withdrawal symptoms, and then will smoke one cigarette (either active nicotine or placebo). Researchers will document participants consumption of the cigarette. After the cigarette is smoked, participants will have a PET scan. Blood samples will be drawn during the PET session.
Read the detailed description
Objective: To determine whether nicotine, at the dose delivered through a cigarette (1-2 mg), will increase the release of endogenous opioids, measured by the displacement of the mu-opioid PET receptor radioligand [(11)C]carfentanil and to determine whether smokers have adaptations in the opioid system compared with nonsmokers.
Study Population: 20 current, daily smoikers and 20 never-smokers who have smoked between 1 and 20 cigarettes in their lifetime.
Design: Double-blind, placebo-controlled, parallel groups design.
Outcome Measures: 1) displacement [(11)C]carfentanil binding, secondary to the release of endorphins by nicotine; 2) upregulation of [(11)C]carfentanil specific binding in smokers compared with nonsmokers; 3) [(11)C]carfentanil specific binding as a function of the mu-opioid receptor A118G polymorphism; and 4) correlation between self-report measures of nicotine effect and [(11)C]carfentanil binding profile.
- Conditions
- Substance-related Discorder
- Being tested
- Nicotine, Carfentanil
- Keywords
- Smoking, Nicotine, Endogenous Opioids, PET Study, Carfentanil
- Medical subject headings
- Smoking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NicotineDrug
CarfentanilDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in carfentanil binding.
Secondary outcomes (1)
Cardiovascular and subjective responses to smoking one cigarette.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2008 (estimated)
- Study start17 Jan 2008
- Study completion8 Jan 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 Substance-related DiscorderStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute on Drug Abuse (NIDA)
- Sponsor type
- US National Institutes of Health
- Collaborators
- Johns Hopkins University
- Responsible party
- Sponsor
- Investigators
- Stephen J Heishman, Ph.D., Principal investigator, National Institute on Drug Abuse (NIDA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00618631
- Sponsor's protocol ID
- 999908060
- Other IDs
- 08-DA-N060
- Status last verified
- 8 Jan 2015
- First submitted
- 17 Feb 2008
- Last updated
- 5 Apr 2018
- Results posted
- No
Publications
Bencherif B, Guarda AS, Colantuoni C, Ravert HT, Dannals RF, Frost JJ. Regional mu-opioid receptor binding in insular cortex is decreased in bulimia nervosa and correlates inversely with fasting behavior. J Nucl Med. 2005 Aug;46(8):1349-51.
PubMed 16085593Champtiaux N, Gotti C, Cordero-Erausquin M, David DJ, Przybylski C, Lena C, Clementi F, Moretti M, Rossi FM, Le Novere N, McIntosh JM, Gardier AM, Changeux JP. Subunit composition of functional nicotinic receptors in dopaminergic neurons investigated with knock-out mice. J Neurosci. 2003 Aug 27;23(21):7820-9. doi: 10.1523/JNEUROSCI.23-21-07820.2003.
PubMed 12944511
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Smoking on Opioid Receptor Binding Using [(11)C]Carfentanil: An Imaging PET Study
- ClinicalTrials.gov ID
- NCT00618631
- Acronym / sponsor ID
- 999908060
- Conditions
- Substance-related Discorder
- Keywords
- Smoking, Nicotine, Endogenous Opioids, PET Study, Carfentanil
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- National Institute on Drug Abuse (NIDA)US National Institutes of Health
- Collaborators
- Johns Hopkins University
- Study start
- 17 Jan 2008
- Study completion
- 8 Jan 2015 (actual)
- First posted
- 20 Feb 2008 (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.
Background:
- Tobacco smoking is one of the most preventable causes of morbidity and mortality in the world, but the addictive property of nicotine is such that fewer than 10 percent of people who attempt to quit smoking remain tobacco-free after 1 year. Researchers are studying the addictive properties of nicotine in an attempt to develop more successful medication therapies for smoking cessation.
- Nicotine acts on chemical receptors in the brain, including opioid receptors that affect the perception of pain. Repeated nicotine administration can cause adaptations in the brain s opioid receptors, which heightens the addictive properties of nicotine and increases the likelihood and severity of withdrawal symptoms associated with smoking cessation. Researchers are interested in using positron emission tomography (PET) scanning to study brain chemical responses to nicotine in current smokers and nonsmokers.
Objectives:
- To study brain chemical activity related to cigarette smoking and nicotine administration.
- To compare the brain chemical activity of current daily smokers with that of nonsmokers.
Eligibility:
- Individuals 21 to 50 years of age who are either current smokers (10 to 25 cigarettes daily for at least 2 years) or have had some exposure to tobacco but have never smoked regularly (may have had a maximum of 20 cigarettes in their lifetime and none in past year).
Design:
- Eligible participants will undergo initial medical and psychological screening and neuropsychological testing before beginning the main phase of the study. Participants will be required to abstain from alcohol and drugs (except caffeine, nicotine, and prescription drugs) for 24 hours before each session, and smokers will refrain from smoking after midnight on the night before each session.
- Session 1: Participants will answer questions about nicotine craving and withdrawal symptoms, followed by a magnetic resonance imaging (MRI) scan to provide baseline information about brain activity.
- Session 2 and 3: Participants will answer questions about nicotine craving and withdrawal symptoms, and then will smoke one cigarette (either active nicotine or placebo). Researchers will document participants consumption of the cigarette. After the cigarette is smoked, participants will have a PET scan. Blood samples will be drawn during the PET session.
Detailed description
Objective: To determine whether nicotine, at the dose delivered through a cigarette (1-2 mg), will increase the release of endogenous opioids, measured by the displacement of the mu-opioid PET receptor radioligand [(11)C]carfentanil and to determine whether smokers have adaptations in the opioid system compared with nonsmokers.
Study Population: 20 current, daily smoikers and 20 never-smokers who have smoked between 1 and 20 cigarettes in their lifetime.
Design: Double-blind, placebo-controlled, parallel groups design.
Outcome Measures: 1) displacement [(11)C]carfentanil binding, secondary to the release of endorphins by nicotine; 2) upregulation of [(11)C]carfentanil specific binding in smokers compared with nonsmokers; 3) [(11)C]carfentanil specific binding as a function of the mu-opioid receptor A118G polymorphism; and 4) correlation between self-report measures of nicotine effect and [(11)C]carfentanil binding profile.
Study design
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
Who may qualify
- Ages
- 21 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 21-50 year old males and females
- smoked 1-20 cigarettes in their life and none in past year
- urine cotinine level less than 30 ng/ml (NicAlert reading less than or equal to 1)
- estimated IQ score greater than or equal to 85 (competent to give informed consent)
- medically and psychologically healthy as determined by screening criteria.
Key exclusion criteria (39 listed)
- interest in reducing or quitting tobacco use
- treatment for nicotine dependence in the past 3 months
- current drug or alcohol abuse or dependence
- consumption of more than 15 alcoholic drinks per week during the past month
- any opiate use in the past 6 months
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 |
|---|---|---|
| Nicotine | Drug | – |
| Carfentanil | Drug | – |
Primary outcome
Changes in carfentanil binding.
1 secondary outcome
Cardiovascular and subjective responses to smoking one cigarette.
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 5 Apr 2018.
- Background: PubMed 16085593Bencherif B, Guarda AS, Colantuoni C, Ravert HT, Dannals RF, Frost JJ. Regional mu-opioid receptor binding in insular cortex is decreased in bulimia nervosa and correlates inversely with fasting behavior. J Nucl Med. 2005 Aug;46(8):1349-51.
- Background: PubMed 12944511Champtiaux N, Gotti C, Cordero-Erausquin M, David DJ, Przybylski C, Lena C, Clementi F, Moretti M, Rossi FM, Le Novere N, McIntosh JM, Gardier AM, Changeux JP. Subunit composition of functional nicotinic receptors in dopaminergic neurons investigated with knock-out mice. J Neurosci. 2003 Aug 27;23(21):7820-9. doi: 10.1523/JNEUROSCI.23-21-07820.2003.
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.
Stephen J Heishman, Ph.D. principal investigator
National Institute on Drug Abuse (NIDA)
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nicotine and Carfentanil in people with Substance-related Discorder, run by National Institute on Drug Abuse (NIDA) at 2 sites 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 10 inclusion and 39 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 5 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Changes in carfentanil binding.. 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 NCT00618631, 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 5 Apr 2018.