Nicotine DependenceNCT01040338
Effects of Nicotine on Brain Opioid Receptors
An observational study of Nicotine Dependence, run by University of Pennsylvania at 1 site in United States.
Trial summary
A substantial body of evidence implicates the endogenous opioid system, and the mu opioid receptor (MOR) in particular, in the reinforcing effects of drugs of abuse, including nicotine. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Nicotine Dependence
- What is being tested?
- Nicotine
- Type of treatment
- Injection or infusion
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2010to Mar 2011
- 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: 24 adult, non-treatment seeking smokers of European ancestry, reporting consumption of ≥10 cigarettes per day for at least the past 6 months.
Who may be able to join
- Non-treatment seeking smokers of European ancestry
- Between 18 and 50 years old
- Smoking at least 10 cigarettes per day for at least the past 6 months
- Able to provide informed consent
- Fluent, English-speaking
- Weight ≤ 300 lbs.
Who cannot join
- Current enrollment or plans to enroll in a smoking cessation program, or use other smoking cessation medications in the next 2 months
- Provide a Carbon Monoxide reading of ≤10 ppm at Medical screening.
- History of substance abuse and/or currently receiving treatment for substance abuse (e.g., alcohol, opioids, cocaine, marijuana, or stimulants)
- Current alcohol consumption that exceeds 25 standard drinks/week
- Providing a breath alcohol concentration (BAC) reading of > 0.01 at any session.
- Women who are pregnant, planning a pregnancy, or lactating; all female subjects shall undergo a urine pregnancy test at each session
Show all 21Show fewer
- Women of child-bearing age must agree in writing to use an approved method of contraception
- History or current diagnosis of psychosis, major current depression or bipolar disorder, ADHD, schizophrenia, or any Axis 1 disorder as identified by the MINI
- Serious or unstable disease within the past 6 months (e.g., cancer [except melanoma], heart disease, HIV)
- History of epilepsy or a seizure disorder
- History or current diagnosis (last 6-months) of abnormal rhythms and/or tachycardia (>100 beats/minute); history or current diagnosis of COPD, cardiovascular disease (stroke, angina, coronary heart disease), heart attack in the last 6 months, uncontrolled hypertension (SBP>150 or DBP>90)
- Any medical or neurological condition that might interfere with the distribution of the radiotracer as determined by the study MD
- Current or past use (within past 12 months) of any medications containing naltrexone or other MOR antagonists (e.g., Revia, Trexan)
- Current use or recent discontinuation (within last 14-days) of the following medications
- Any form of smoking cessation medication (Zyban, Wellbutrin, Wellbutrin SR, Chantix, NRT)
- Recent (within last 2 weeks) or planned use of psychotropic medications (anti-psychotics, anti-depressants (tricyclic, SSRI, MAOI), anti-anxiety or panic medications, and stimulants (e.g., Provigil, Ritalin), and opiate-containing medications for chronic pain
- Allergic response to any form of opioids or naloxone
- Participants shall be instructed to refrain from using any study prohibited drugs (note - participants are allowed to take prescription medicines not in the exclusion list) throughout their participation in the study.
- Self-reported history of head trauma or prior seizure, brain (or CNS) tumor
- Self-reported history of claustrophobia (contraindicated for PET)
- Inability to complete the baseline study procedures within four hours and/or correctly, as determined by the principal investigator.
Trial locations and contacts
1 site in 1 country.
United States1 site
Center for Interdisciplinary Research on Nicotine Addiction, University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: Functional Characterization of OPRM1 A118G in Nicotine Dependence: IV Nicotine Study
A substantial body of evidence implicates the endogenous opioid system, and the mu opioid receptor (MOR) in particular, in the reinforcing effects of drugs of abuse, including nicotine. A single nucleotide polymorphism (SNP) in the mu opioid receptor gene (OPRM1 Asp40) is associated with the ability to quit smoking, as well as nicotine reward and withdrawal symptoms. However, the precise mechanism through which this SNP influences nicotine dependence remains unresolved. This positron emission tomography (PET) study will examine whether this OPRM1 SNP alters MOR binding in response to nicotine in human smokers. Specifically, we will use [11 C]carfentanil PET imaging to assess the effects of intravenous (IV) nicotine versus saline (within-subject) on MOR binding potential in 24 chronic smokers genotyped prospectively and stratified by OPRM1 genotype.
Read the detailed description
The study uses a mixed factorial design with one between subject factor (OPRM1 genotype_: Asn40/Asn40 vs. Asn40/Asp40 or Asp40/Asp40) and one within-subject factor (IV nicotine vs. IV saline) to examine genotype by nicotine interactions on MOR binding potential (BP_ND ) assessed via PET imaging with [11 C]carfentanil. Twenty-four smokers (12 male, 12 female; 12 from each genotype group) will participate in two 90 minute PET sessions following overnight (14-hours) abstinence from nicotine. Genotype groups will be matched for age and sex . One week prior to the first PET session, there will be an adaptation session during which participants will receive IV saline followed 30 minutes later by IV nicotine (1 mg/70 kg) to ensure that they tolerate the procedure. In the PET sessions, participants will receive either IV nicotine (1 mg/70 kg) or saline (within-subject, double blind, counterbalanced). The primary outcomes will be BP_ND in ventral striatum and anterior cingulate cortex (ACC). Normally menstruating women will be scheduled for their sessions during the early follicular phase. Sessions will be separated by 1 month for all participants to reduce variability in MOR binding due to hormonal changes during females menstrual cycles. Participants will complete subjective measures of nicotine reward and craving at each session.
- Conditions
- Nicotine Dependence
- Being tested
- Nicotine
- Keywords
- Smoking, Tobacco, Nicotine, Dependence, Genetics
- Medical subject headings
- Tobacco Use Disorder, Smoking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NicotineDrug
Participants shall receive an intravenous injection of nicotine during their practice session and one of their PET scans (double-blind). The dose of IV nicotine will be 1mg/70kg and the maximum dose that shall be injected is 1.2mg.
| Study group | Role | What they receive |
|---|---|---|
| OPRM1 A118G AA genotype | Individuals with the AA genotype at the OPRM1 A118G polymorphism. Receives: Drug: Nicotine | |
| OPRM1 A118G AG or GG genotype | Individuals with the */G allele at the OPRM1 A118G polymorphism Receives: Drug: Nicotine |
What is being measured
The primary outcome is the main question the study is designed to answer.
MOR binding potential
Measured: 5/31/2011
Secondary outcomes (1)
Subjective reward/liking and cravings to smoke
Measured: 5/31/2011
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2009 (estimated)
- Study startFeb 2010
- Primary completionMar 2011
- Study completionMar 2011
Why it stopped: Issues \& unreliability with \[11C\]Carfentanil production
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nicotine DependenceStudies 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
- Case crossover
- Time perspective
- Prospective
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Caryn Lerman, PhD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01040338
- Sponsor's protocol ID
- 809187
- Other IDs
- R21DA027066
- Status last verified
- Apr 2019
- First submitted
- 24 Dec 2009
- Last updated
- 11 Apr 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Functional Characterization of OPRM1 A118G in Nicotine Dependence: IV Nicotine Study
- ClinicalTrials.gov ID
- NCT01040338
- Acronym / sponsor ID
- 809187
- Conditions
- Nicotine Dependence
- Keywords
- Smoking, Tobacco, Nicotine, Dependence, Genetics
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Issues \& unreliability with \[11C\]Carfentanil production
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- Feb 2010
- Primary completion
- Mar 2011 (actual)
- Study completion
- Mar 2011 (actual)
- First posted
- 29 Dec 2009 (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.
A substantial body of evidence implicates the endogenous opioid system, and the mu opioid receptor (MOR) in particular, in the reinforcing effects of drugs of abuse, including nicotine. A single nucleotide polymorphism (SNP) in the mu opioid receptor gene (OPRM1 Asp40) is associated with the ability to quit smoking, as well as nicotine reward and withdrawal symptoms. However, the precise mechanism through which this SNP influences nicotine dependence remains unresolved. This positron emission tomography (PET) study will examine whether this OPRM1 SNP alters MOR binding in response to nicotine in human smokers. Specifically, we will use [11 C]carfentanil PET imaging to assess the effects of intravenous (IV) nicotine versus saline (within-subject) on MOR binding potential in 24 chronic smokers genotyped prospectively and stratified by OPRM1 genotype.
Detailed description
The study uses a mixed factorial design with one between subject factor (OPRM1 genotype_: Asn40/Asn40 vs. Asn40/Asp40 or Asp40/Asp40) and one within-subject factor (IV nicotine vs. IV saline) to examine genotype by nicotine interactions on MOR binding potential (BP_ND ) assessed via PET imaging with [11 C]carfentanil. Twenty-four smokers (12 male, 12 female; 12 from each genotype group) will participate in two 90 minute PET sessions following overnight (14-hours) abstinence from nicotine. Genotype groups will be matched for age and sex . One week prior to the first PET session, there will be an adaptation session during which participants will receive IV saline followed 30 minutes later by IV nicotine (1 mg/70 kg) to ensure that they tolerate the procedure. In the PET sessions, participants will receive either IV nicotine (1 mg/70 kg) or saline (within-subject, double blind, counterbalanced). The primary outcomes will be BP_ND in ventral striatum and anterior cingulate cortex (ACC). Normally menstruating women will be scheduled for their sessions during the early follicular phase. Sessions will be separated by 1 month for all participants to reduce variability in MOR binding due to hormonal changes during females menstrual cycles. Participants will complete subjective measures of nicotine reward and craving at each session.
Study design
- Observational model
- Case crossover
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| OPRM1 A118G AA genotype | – | Drug: NicotineIndividuals with the AA genotype at the OPRM1 A118G polymorphism. |
| OPRM1 A118G AG or GG genotype | – | Drug: NicotineIndividuals with the */G allele at the OPRM1 A118G polymorphism |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- 24 adult, non-treatment seeking smokers of European ancestry, reporting consumption of ≥10 cigarettes per day for at least the past 6 months.
Key inclusion criteria (6 listed)
- Non-treatment seeking smokers of European ancestry
- Between 18 and 50 years old
- Smoking at least 10 cigarettes per day for at least the past 6 months
- Able to provide informed consent
- Fluent, English-speaking
Key exclusion criteria (21 listed)
- Current enrollment or plans to enroll in a smoking cessation program, or use other smoking cessation medications in the next 2 months
- Provide a Carbon Monoxide reading of ≤10 ppm at Medical screening.
- History of substance abuse and/or currently receiving treatment for substance abuse (e.g., alcohol, opioids, cocaine, marijuana, or stimulants)
- Current alcohol consumption that exceeds 25 standard drinks/week
- Providing a breath alcohol concentration (BAC) reading of > 0.01 at any session.
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 |
|---|---|---|
| NicotineParticipants shall receive an intravenous injection of nicotine during their practice session and one of their PET scans (double-blind). The dose of IV nicotine will be 1mg/70kg and the maximum dose that shall be injected is 1.2mg. | Drug | OPRM1 A118G AA genotype, OPRM1 A118G AG or GG genotype |
Primary outcome
MOR binding potential
Time frame: 5/31/2011
1 secondary outcome
Subjective reward/liking and cravings to smoke
Time frame: 5/31/2011
Results and safety
The study was stopped early (reason given: Issues \& unreliability with \[11C\]Carfentanil production). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2019.
- Center 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.
Caryn Lerman, PhD 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 Dependence, 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 6 inclusion and 21 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: stopped early, as of the sponsor's last update on 11 Apr 2019. 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 was stopped early (reason given: Issues \& unreliability with \[11C\]Carfentanil production). Results are not available in the source record.
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?
MOR binding potential (time frame: 5/31/2011). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Apr 2019.