Nicotine DependencePhase 4NCT01048944
Nicotine Replacement Therapy (NRT) and Bupropion Mechanisms of Effectiveness in Smokers
A Phase 4 study testing Bupropion SR and Nicotine Patch in people with Nicotine Dependence, run by Southern Illinois University Carbondale at 1 site in United States.
Trial summary
The purpose of this study is to better characterize differences in mood, attention, brain activation patterns underlying the beneficial effects of pharmacological treatments previously demonstrated to be help individuals successfully quit tobacco smoking. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Nicotine Dependence
- What is being tested?
- Bupropion SR and Nicotine Patch
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 197 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2005to Jan 2013
- 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 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-IV) diagnosis of nicotine dependence with psychological dependence
- Smokes at least 10 cigarettes per day for the three months prior to enrollment
- Currently seeking treatment for nicotine dependence
- Medically healthy on the basis of physical examination and medical history, vital signs,
- Females must use an effective method of contraception for the duration of the study
Who cannot join
- DSM-IV diagnosis of abuse or dependence on alcohol or drugs other than nicotine
- Current Axis I diagnosis or current treatment with psychotropic medications within the three months prior to enrollment
- History of schizophrenia or other psychotic disorders, bipolar disorder, or anxiety disorders
- Currently seeking treatment for nicotine disorders
- History of seizures or head trauma with loss of consciousness, brain contusion, or fracture
- History of significant recent violent behavior
Show all 10Show fewer
- Blood pressure greater than 150/90
- History of eating disorders
- History of allergic reaction to any of the study medications
- Pregnant
Trial locations and contacts
1 site in 1 country.
United States1 site
Southern Illinois University
Carbondale, Illinois, 62901-6502
About this study
Official title: NRT & Bupropion Mechanisms of Effectiveness in Smokers: Phase IV Trial
The purpose of this study is to better characterize differences in mood, attention, brain activation patterns underlying the beneficial effects of pharmacological treatments previously demonstrated to be help individuals successfully quit tobacco smoking. Smokers will be randomly assigned to one of three treatments: 1) bupropion sustained release (SR), 2) nicotine patch, or 3) placebo patches plus pills across a 45-day period with a 3-week intensive post-treatment follow-up. In addition, 20 percent of the subjects will be randomized to a delayed-quit control group.
Read the detailed description
The first aim of this revised proposal is to accurately assess the duration and trajectories of smoking abstinence symptoms and associated biobehavioral indices across 66 days of quitting smoking in 3 different treatment groups: 1) bupropion SR (BUP), 2) transdermal nicotine patch (TNP), and 3) placebo patch plus placebo pill. Study sensitivity and accuracy will be maximized by using procedures designed to maximize abstinence and minimize study dropout. The second aim is to characterize brain and psychological mechanisms by which BUP and TNP promote abstinence. While the efficacies of BUP and TNP in promoting smoking abstinence have been repeatedly demonstrated, little is known about the mechanisms mediating this efficacy. The final primary goal of this competitive continuation proposal is to characterize individual differences in psychological and brain mechanisms mediating the beneficial effects of BUP and TNP on smoking abstinence and withdrawal symptoms. A secondary goal is to assess the ability of a battery of innovative brain and biobehavioral measures of attention and affect to predict relapse.
To achieve these goals, the effects of quitting smoking with or without the help of TNP and BUP will be assessed intensively across 66 days of abstinence. Dependent measures will be mood, vigilance, attentional bias to smoking and emotional stimuli, and related physiological measures (resting EEG activation and activation asymmetry indices of affective states and traits, and event-related potential activity elicited by emotional and smoking stimuli). Smokers will be randomly assigned to one of three immediate-quit groups (N = 60 per group): (1) bupropion + placebo patch, (2) placebo pill + nicotine patch, and (3) placebo patch + placebo pill; or to a fourth (control) group (N = 40) that will quit after the final experimental session (after the other subjects have completed their 66-day* abstinence period). Subjects in the 3 treatment groups and the control group will have the same set of biobehavioral measures assessed during the experimental sessions at the same points in time. It is hypothesized that BUP and TNP will have both common and unique mechanisms by which they reduce withdrawal symptoms and that gender and personality traits will moderate the effects of these treatments. (Note.* To avoid final-session mood and arousal effects subjects will actually quit for 67 days, but biobehavioral measures will be collected on the 66th day of abstinence.)
- Conditions
- Nicotine Dependence
- Being tested
- Bupropion SR, Nicotine Patch, Placebo Patch and Placebo Pill
- Keywords
- Electroencephalography, nicotine, bupropion, attention, drug withdrawal symptoms
- Medical subject headings
- Tobacco Use Disorder, Substance Withdrawal Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bupropion SRDrug
Also called ZybanSR
150 encapsulated pill,3 days 1x/day then 56/day for 2x/day, then 3 day 1x/day ramp-down.
Nicotine PatchDrug
Also called NicodermCQ
Nicotine patch beginning 1st day cessation: 21 mg/24 days, 14 mg/14 days, 7 mg/7 days
Placebo Patch and Placebo PillDrug
Also called Placebo
150 encapsulated placebo pill,3 days 1x/day then 56/day for 2x/day, then 3 day 1x/day ramp-down. Placebo patch beginning 1st day cessation: 21 mg/24 days, 14 mg/14 days, 7 mg/7 days. The placebo patches were given beginning 1st day cessation: 21 mg size (but actually placebo)/24 days, 14 mg size (actually placebo)/ 14 mg size (actually placebo) 14 days/, 7 mg size (actually placebo)/7 days
| Study group | Role | What they receive |
|---|---|---|
| Bupropion SR | Active comparator | 150 mg bid bupropion SR Receives: Drug: Bupropion SR |
| Nicotine Patch | Active comparator | 21mg, 14mg, 7mg Receives: Drug: Nicotine Patch |
| Placebo Patch and Placebo Pill | Placebo comparator | Individuals were placed on both a placebo patch that were the same size as active patches given to the Nicotine Patch group and were also given placebo pills were the same size and identically packaged as the active pills (bupropion) given to the Bupropion SR group. Receives: Drug: Placebo Patch and Placebo Pill |
| Delayed-quit control | No intervention | Smoke for 67 days while others have quit, then quit. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Log Brain-wave (EEG) Activity (Power [Microvolts Squared]) From Pre-quit Baseline to 66 Days Post-quit, Assessed at 3, 24, 45, and 66 Days Post-quit.
Brain-wave activity (EEG) was assessed using electrodes on the subject's scalp, the outputs of which were and quantified by a commercial brain wave machine. EEG was collected at frontal (e.g., Fz) and parietal (e.g., Pz) electrodes while subjects relaxed. EEG was analyzed using computer programs that measured slow-frequency EEG waves known as delta (1.5-4.5 cycles/second [cps]), theta-1 (4.5-6.0 cps), theta-2 (6.0-7.7 cps), and alpha-1 (7.8-10.0 cps), and higher frequency waves. Generally, delta, alpha-1 and theta waves reflect deactivation of the brain activity, while higher frequency waves reflect greater brain activation. Brain activity was quantified as the natural log of EEG power [microvolts squared] as determined by the fast Fourier mathematical algorithm. Days post quit were components of Time. The primary focus was on changes in the individual subject's log theta-1, theta-2, and alpha-1 power at post-quit points in time minus the log values at the pre-quite baseline.
Measured: Mean EEG power [microvolts squared] from at baseline, 3, 24, 45, and 66 days post-quit
Changes in Log of Smoking Withdrawal Scores (Mood, and Depressive Symptoms) From Baseline Across 66 Days of Abstinence
Changes in log from baseline in the widely used Shiffman-Jarvik Withdrawal "craving" and "psychological symptom" scores through 66 days of abstinence. Post-quit changes were assessed at days 3, 24, 45, and 66 of abstinence. The maximal range of value raw for craving is from "5" = (no craving) to "47" (maximally strong craving), while that for psychological symptoms is from "5" (no symptoms) to "60" (maximally intense symptoms of across multiple symptoms). Because the subtraction of logs is equivalent to the ratio of the two scores, a difference in logs (base 10) with a value of "1" is equal to an increase by a factor of 10, while a value of "0" is no change, and values of less than "0" are decreases below baseline values.
Measured: Changes in log withdrawal symptoms from baseline through 66 days of abstinence
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2010 (estimated)
- Study startJun 2005
- Primary completionJan 2013
- Study completionJan 2013
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Nicotine DependenceStudies 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 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 197 participants (actual)
Sponsor and investigators
- Lead sponsor
- Southern Illinois University Carbondale
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Principal investigator, David Gilbert, Southern Illinois University Carbondale
- Investigators
- David G Gilbert, PhD, Principal investigator, Southern Illinois University Carbondale
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01048944
- Sponsor's protocol ID
- NIH/NIDA-2R01DA012289
- Other IDs
- 2R01DA012289
- Status last verified
- Nov 2014
- First submitted
- 13 Jan 2010
- Last updated
- 25 Nov 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Gilbert DG, Rabinovich NE, Gilbert-Matuskowitz EA, Klein KP, Pergadia ML. Smoking abstinence symptoms across 67 days compared with randomized controls-Moderation by nicotine replacement therapy, bupropion, and negative-affect traits. Exp Clin Psychopharmacol. 2019 Dec;27(6):536-551. doi: 10.1037/pha0000278. Epub 2019 Mar 28.
PubMed 30920255
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NRT & Bupropion Mechanisms of Effectiveness in Smokers: Phase IV Trial
- ClinicalTrials.gov ID
- NCT01048944
- Acronym / sponsor ID
- NIH/NIDA-2R01DA012289
- Conditions
- Nicotine Dependence
- Keywords
- Electroencephalography, nicotine, bupropion, attention, drug withdrawal symptoms
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 197 participants (actual)
- Lead sponsor
- Southern Illinois University CarbondaleUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- Jun 2005
- Primary completion
- Jan 2013 (actual)
- Study completion
- Jan 2013 (actual)
- First posted
- 14 Jan 2010 (estimated)
- Results
- Posted 25 Nov 2014
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 this study is to better characterize differences in mood, attention, brain activation patterns underlying the beneficial effects of pharmacological treatments previously demonstrated to be help individuals successfully quit tobacco smoking. Smokers will be randomly assigned to one of three treatments: 1) bupropion sustained release (SR), 2) nicotine patch, or 3) placebo patches plus pills across a 45-day period with a 3-week intensive post-treatment follow-up. In addition, 20 percent of the subjects will be randomized to a delayed-quit control group.
Detailed description
The first aim of this revised proposal is to accurately assess the duration and trajectories of smoking abstinence symptoms and associated biobehavioral indices across 66 days of quitting smoking in 3 different treatment groups: 1) bupropion SR (BUP), 2) transdermal nicotine patch (TNP), and 3) placebo patch plus placebo pill. Study sensitivity and accuracy will be maximized by using procedures designed to maximize abstinence and minimize study dropout. The second aim is to characterize brain and psychological mechanisms by which BUP and TNP promote abstinence. While the efficacies of BUP and TNP in promoting smoking abstinence have been repeatedly demonstrated, little is known about the mechanisms mediating this efficacy. The final primary goal of this competitive continuation proposal is to characterize individual differences in psychological and brain mechanisms mediating the beneficial effects of BUP and TNP on smoking abstinence and withdrawal symptoms. A secondary goal is to assess the ability of a battery of innovative brain and biobehavioral measures of attention and affect to predict relapse.
To achieve these goals, the effects of quitting smoking with or without the help of TNP and BUP will be assessed intensively across 66 days of abstinence. Dependent measures will be mood, vigilance, attentional bias to smoking and emotional stimuli, and related physiological measures (resting EEG activation and activation asymmetry indices of affective states and traits, and event-related potential activity elicited by emotional and smoking stimuli). Smokers will be randomly assigned to one of three immediate-quit groups (N = 60 per group): (1) bupropion + placebo patch, (2) placebo pill + nicotine patch, and (3) placebo patch + placebo pill; or to a fourth (control) group (N = 40) that will quit after the final experimental session (after the other subjects have completed their 66-day* abstinence period). Subjects in the 3 treatment groups and the control group will have the same set of biobehavioral measures assessed during the experimental sessions at the same points in time. It is hypothesized that BUP and TNP will have both common and unique mechanisms by which they reduce withdrawal symptoms and that gender and personality traits will moderate the effects of these treatments. (Note.* To avoid final-session mood and arousal effects subjects will actually quit for 67 days, but biobehavioral measures will be collected on the 66th day of abstinence.)
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Bupropion SR | Active comparator | Drug: Bupropion SR150 mg bid bupropion SR |
| Nicotine Patch | Active comparator | Drug: Nicotine Patch21mg, 14mg, 7mg |
| Placebo Patch and Placebo Pill | Placebo comparator | Drug: Placebo Patch and Placebo PillIndividuals were placed on both a placebo patch that were the same size as active patches given to the Nicotine Patch group and were also given placebo pills were the same size and identically packaged as the active pills (bupropion) given to the Bupropion SR group. |
| Delayed-quit control | No intervention | –Smoke for 67 days while others have quit, then quit. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-IV) diagnosis of nicotine dependence with psychological dependence
- Smokes at least 10 cigarettes per day for the three months prior to enrollment
- Currently seeking treatment for nicotine dependence
- Medically healthy on the basis of physical examination and medical history, vital signs,
- Females must use an effective method of contraception for the duration of the study
Key exclusion criteria (10 listed)
- DSM-IV diagnosis of abuse or dependence on alcohol or drugs other than nicotine
- Current Axis I diagnosis or current treatment with psychotropic medications within the three months prior to enrollment
- History of schizophrenia or other psychotic disorders, bipolar disorder, or anxiety disorders
- Currently seeking treatment for nicotine disorders
- History of seizures or head trauma with loss of consciousness, brain contusion, or fracture
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 |
|---|---|---|
| Bupropion SRAlso: ZybanSR150 encapsulated pill,3 days 1x/day then 56/day for 2x/day, then 3 day 1x/day ramp-down. | Drug | Bupropion SR |
| Nicotine PatchAlso: NicodermCQNicotine patch beginning 1st day cessation: 21 mg/24 days, 14 mg/14 days, 7 mg/7 days | Drug | Nicotine Patch |
| Placebo Patch and Placebo PillAlso: Placebo150 encapsulated placebo pill,3 days 1x/day then 56/day for 2x/day, then 3 day 1x/day ramp-down. Placebo patch beginning 1st day cessation: 21 mg/24 days, 14 mg/14 days, 7 mg/7 days. The placebo patches were given beginning 1st day cessation: 21 mg size (but actually placebo)/24 days, 14 mg size (actually placebo)/ 14 mg size (actually placebo) 14 days/, 7 mg size (actually placebo)/7 days | Drug | Placebo Patch and Placebo Pill |
Primary outcome
Changes in Log Brain-wave (EEG) Activity (Power [Microvolts Squared]) From Pre-quit Baseline to 66 Days Post-quit, Assessed at 3, 24, 45, and 66 Days Post-quit.
Time frame: Mean EEG power [microvolts squared] from at baseline, 3, 24, 45, and 66 days post-quit
Brain-wave activity (EEG) was assessed using electrodes on the subject's scalp, the outputs of which were and quantified by a commercial brain wave machine. EEG was collected at frontal (e.g., Fz) and parietal (e.g., Pz) electrodes while subjects relaxed. EEG was analyzed using computer programs that measured slow-frequency EEG waves known as delta (1.5-4.5 cycles/second [cps]), theta-1 (4.5-6.0 cps), theta-2 (6.0-7.7 cps), and alpha-1 (7.8-10.0 cps), and higher frequency waves. Generally, delta, alpha-1 and theta waves reflect deactivation of the brain activity, while higher frequency waves reflect greater brain activation. Brain activity was quantified as the natural log of EEG power [microvolts squared] as determined by the fast Fourier mathematical algorithm. Days post quit were components of Time. The primary focus was on changes in the individual subject's log theta-1, theta-2, and alpha-1 power at post-quit points in time minus the log values at the pre-quite baseline.
Changes in Log of Smoking Withdrawal Scores (Mood, and Depressive Symptoms) From Baseline Across 66 Days of Abstinence
Time frame: Changes in log withdrawal symptoms from baseline through 66 days of abstinence
Changes in log from baseline in the widely used Shiffman-Jarvik Withdrawal "craving" and "psychological symptom" scores through 66 days of abstinence. Post-quit changes were assessed at days 3, 24, 45, and 66 of abstinence. The maximal range of value raw for craving is from "5" = (no craving) to "47" (maximally strong craving), while that for psychological symptoms is from "5" (no symptoms) to "60" (maximally intense symptoms of across multiple symptoms). Because the subtraction of logs is equivalent to the ratio of the two scores, a difference in logs (base 10) with a value of "1" is equal to an increase by a factor of 10, while a value of "0" is no change, and values of less than "0" are decreases below baseline values.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30920255Gilbert DG, Rabinovich NE, Gilbert-Matuskowitz EA, Klein KP, Pergadia ML. Smoking abstinence symptoms across 67 days compared with randomized controls-Moderation by nicotine replacement therapy, bupropion, and negative-affect traits. Exp Clin Psychopharmacol. 2019 Dec;27(6):536-551. doi: 10.1037/pha0000278. Epub 2019 Mar 28.
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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.
David G Gilbert, PhD principal investigator
Southern Illinois University Carbondale
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 Bupropion SR and Nicotine Patch in people with Nicotine Dependence, run by Southern Illinois University Carbondale 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 5 inclusion and 10 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 25 Nov 2014. 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 25 Nov 2014). 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?
Changes in Log Brain-wave (EEG) Activity (Power [Microvolts Squared]) From Pre-quit Baseline to 66 Days Post-quit, Assessed at 3, 24, 45, and 66 Days Post-quit. (time frame: Mean EEG power [microvolts squared] from at baseline, 3, 24, 45, and 66 days post-quit). The study lists 2 primary outcomes in all. 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 NCT01048944, which also lists 1 linked publication.
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 25 Nov 2014.