Nicotine DependencePhase 4NCT01664741
Nicotine Dependence, Withdrawal and Replacement Therapy Assessed by PET Imaging
A Phase 4 study testing Nicotine patch - transdermal in people with Nicotine Dependence, run by Johns Hopkins University at 1 site in United States.
Trial summary
The proposed research will provide significant new gender-specific information of scientific and clinical relevance on the function of the mu-opioid system in nicotine dependence and therapeutic effectiveness of nicotine replacement therapy (NRT). Read more about this study
- Who is it for?
- Ages 21 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Nicotine Dependence
- What is being tested?
- Nicotine patch - transdermal
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 127 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2012to Dec 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 21 - 60 years old
- must meet DSM-IV criteria for nicotine dependence and be actively smoking
- Exclusion Criteria: subjects must meet study guidelines for medical and mental health status.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins University School of Medicine
Baltimore, Maryland, 21205
About this study
The proposed research will provide significant new gender-specific information of scientific and clinical relevance on the function of the mu-opioid system in nicotine dependence and therapeutic effectiveness of nicotine replacement therapy (NRT). The studies will help to explain the differences in the prevalence of smoking in men and women, sex-specific differences in nicotine craving and withdrawal as well as the poorer therapeutic response to NRT. This work may pave the way to the design of improved pharmacotherapies that can more effectively target the endogenous opioid system in the treatment of nicotine dependence.
Read the detailed description
While smoking prevalence has declined for both men and women over the last two decades, rates among women have shown a much shallower decrease and, in recent years, prevalence of cigarette initiation has been higher for girls than boys. Smoking among women of child-bearing age has significant negative health consequences for mother and child, increasing fetal and infant morbidity and mortality. Women are both less likely to initiate a quit attempt and more likely to relapse if these women do quit. Nicotine replacement therapy (NRT), still the most widely used smoking treatment intervention in the United States, is less effective for women compared with men, and women report less craving reduction on NRT. The endogenous opioid system is involved in smoking initiation, nicotine craving and reward as well as nicotine withdrawal symptoms. Interestingly, research suggests that sexual dimorphic features of the endogenous mu-opioid system may in part explain gender differences in nicotine effects. To better understand the role of the mu-opioid system in poorer NRT responses in women, this proposal will examine NRT effects on mu opioid receptor binding potential (MOR BP) in female compared to male smokers during active versus placebo NRT. Specifically, nicotine dependent women and men in active smoking status will undergo PET imaging for MOR BP measurement using 11C-carfentanil. Following baseline PET measurement in active smoking (scan 1), smokers will be randomized to active or placebo nicotine replacement therapy ((A-NRT or P-NRT); 72 hours later, a second scan will be obtained. As a reference group, demographically-matched women and men who have never smoked will undergo two scans as well. Behavioral measurements of nicotine reward, craving and withdrawal will be obtained repeatedly across the protocol. The proposed research will provide significant new, gender-specific information of scientific and clinical relevance on the function of the mu-opioid system in nicotine dependence and therapeutic effectiveness of nicotine replacement therapy.
- Conditions
- Nicotine Dependence
- Being tested
- Nicotine patch - transdermal, placebo
- Keywords
- Nicotine dependence, cigarette, smoking, nicotine replacement therapy, positron emission tomography
- 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.
Nicotine patch - transdermalDrug
Also called Nicotine Replacement Therapy (NRT)
21 mg patch
placeboDrug
| Study group | Role | What they receive |
|---|---|---|
| Nicotine patch - transdermal | Active comparator | 21 mg nicotine patch Receives: Drug: Nicotine patch - transdermal |
| Placebo NRT | Placebo comparator | Matching placebo patch Receives: Drug: placebo |
| Healthy non-smoker comparison | No intervention | Demographically-matched women and men who have never smoked |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Mu-opioid Receptor Binding Potential (BP) Between Baseline and Post-patch Scans
BP provides an estimate of the product of the density of available receptors (Bmax' or the receptor density Bmax less those occupied by endogenous transmitters) and the affinity [1/equilibrium dissociation constant (KD)]. We use reference tissue graphical analysis (RTGA) to obtain regional BP values using occipital lobe as a reference region. Negative BP change means means a decrease in the BP and positive BP change means an increase in the BP.
Measured: 90 minutes
Secondary outcomes (2)
Relationship Between Change in Mu-opioid Receptor Binding Potential and Visual Analog Craving Scale Score
Regression measure (β) between change in mu-opioid receptor binding potential between baseline scan and post-treatment scan in the left amygdala and mean Craving Visual Analog Scale score on Days 2 - 4 of the Clinical Research Unit stay. Craving visual analog scale ranges from 0 (not at all) to 20 (worst ever).
Measured: 72 hours
Relationship Between Change in Mu-opioid Receptor Binding Potential and Minnesota Nicotine Withdrawal Scale Score
Regression measure (β) between change in mu-opioid receptor binding potential between baseline scan and post-treatment scan and mean Minnesota Nicotine Withdrawal Scale (MNWS) score on Days 2 - 4 of the Clinical Research Unit stay. The MNWS is a self-report measure that consists of 14 nicotine withdrawal symptoms each rated on a 0 - 4 response scale for severity over the past 24 hours. Higher scores are indicative of greater nicotine withdrawal severity.
Measured: 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2012 (estimated)
- Study startApr 2012
- Primary completionMay 2018
- Study completionDec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Nicotine DependenceStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 127 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Mary E McCaul, Ph.D., Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01664741
- Sponsor's protocol ID
- NA_00036996
- Other IDs
- R01DA026823
- Status last verified
- Apr 2019
- First submitted
- 10 Aug 2012
- Last updated
- 9 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nicotine Dependence, Withdrawal and Replacement Therapy Assessed by PET Imaging
- ClinicalTrials.gov ID
- NCT01664741
- Acronym / sponsor ID
- NA_00036996
- Conditions
- Nicotine Dependence
- Keywords
- Nicotine dependence, cigarette, smoking, nicotine replacement therapy, positron emission tomography
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 127 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- Apr 2012 (actual)
- Primary completion
- May 2018 (actual)
- Study completion
- Dec 2018 (actual)
- First posted
- 14 Aug 2012 (estimated)
- Results
- Posted 9 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The proposed research will provide significant new gender-specific information of scientific and clinical relevance on the function of the mu-opioid system in nicotine dependence and therapeutic effectiveness of nicotine replacement therapy (NRT). The studies will help to explain the differences in the prevalence of smoking in men and women, sex-specific differences in nicotine craving and withdrawal as well as the poorer therapeutic response to NRT. This work may pave the way to the design of improved pharmacotherapies that can more effectively target the endogenous opioid system in the treatment of nicotine dependence.
Detailed description
While smoking prevalence has declined for both men and women over the last two decades, rates among women have shown a much shallower decrease and, in recent years, prevalence of cigarette initiation has been higher for girls than boys. Smoking among women of child-bearing age has significant negative health consequences for mother and child, increasing fetal and infant morbidity and mortality. Women are both less likely to initiate a quit attempt and more likely to relapse if these women do quit. Nicotine replacement therapy (NRT), still the most widely used smoking treatment intervention in the United States, is less effective for women compared with men, and women report less craving reduction on NRT. The endogenous opioid system is involved in smoking initiation, nicotine craving and reward as well as nicotine withdrawal symptoms. Interestingly, research suggests that sexual dimorphic features of the endogenous mu-opioid system may in part explain gender differences in nicotine effects. To better understand the role of the mu-opioid system in poorer NRT responses in women, this proposal will examine NRT effects on mu opioid receptor binding potential (MOR BP) in female compared to male smokers during active versus placebo NRT. Specifically, nicotine dependent women and men in active smoking status will undergo PET imaging for MOR BP measurement using 11C-carfentanil. Following baseline PET measurement in active smoking (scan 1), smokers will be randomized to active or placebo nicotine replacement therapy ((A-NRT or P-NRT); 72 hours later, a second scan will be obtained. As a reference group, demographically-matched women and men who have never smoked will undergo two scans as well. Behavioral measurements of nicotine reward, craving and withdrawal will be obtained repeatedly across the protocol. The proposed research will provide significant new, gender-specific information of scientific and clinical relevance on the function of the mu-opioid system in nicotine dependence and therapeutic effectiveness of nicotine replacement therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Nicotine patch - transdermal | Active comparator | Drug: Nicotine patch - transdermal21 mg nicotine patch |
| Placebo NRT | Placebo comparator | Drug: placeboMatching placebo patch |
| Healthy non-smoker comparison | No intervention | –Demographically-matched women and men who have never smoked |
Who may qualify
- Ages
- 21 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 21 - 60 years old
- must meet DSM-IV criteria for nicotine dependence and be actively smoking
- Exclusion Criteria: subjects must meet study guidelines for medical and mental health status.
Key exclusion criteria (0 listed)
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 patch - transdermalAlso: Nicotine Replacement Therapy (NRT)21 mg patch | Drug | Nicotine patch - transdermal |
| placebo | Drug | Placebo NRT |
Primary outcome
Change in Mu-opioid Receptor Binding Potential (BP) Between Baseline and Post-patch Scans
Time frame: 90 minutes
BP provides an estimate of the product of the density of available receptors (Bmax' or the receptor density Bmax less those occupied by endogenous transmitters) and the affinity [1/equilibrium dissociation constant (KD)]. We use reference tissue graphical analysis (RTGA) to obtain regional BP values using occipital lobe as a reference region. Negative BP change means means a decrease in the BP and positive BP change means an increase in the BP.
2 secondary outcomes
Relationship Between Change in Mu-opioid Receptor Binding Potential and Visual Analog Craving Scale Score
Time frame: 72 hours
Relationship Between Change in Mu-opioid Receptor Binding Potential and Minnesota Nicotine Withdrawal Scale Score
Time frame: 72 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Mary E McCaul, Ph.D. principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Nicotine patch - transdermal in people with Nicotine Dependence, run by Johns Hopkins University 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 3 inclusion and 0 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 9 May 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Mu-opioid Receptor Binding Potential (BP) Between Baseline and Post-patch Scans (time frame: 90 minutes). 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 9 May 2019.