Nicotine DependencePhase 3ConNicBrainNCT01406223

Mechanistic Evaluations of Pre-Cessation Therapies for Smoking Cessation

A Phase 3 study testing Varenicline, Bupropion and Nicotine patches in people with Nicotine Dependence, run by Duke University at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to look at brain function in order to understand how different treatments work to help people quit smoking. In this study, the investigators will look at the effects of nicotine patches, Chantix alone or Chantix paired with Zyban. Read more about this study

Who is it for?: Ages 18 to 50 years
Conditions the study is for: Nicotine Dependence
What is being tested?: Varenicline, Bupropion and Nicotine patches
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 282 participants
Where: 2 sitesUnited States
Study dates: Jul 2011to Jun 2014
Phase: Phase 3
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 50 years
All sexes
No healthy volunteers
Adult

Who may be able to join

Are generally healthy;
Are 18-50 years old;
Smoke an average of at least 10 cigarettes per day for at least three cumulative years;
Have an afternoon expired air carbon monoxide (CO) reading of at least 10ppm;
Are right-handed as measured by a two-item scale used in our laboratory;
Express a desire to quit smoking in the next thirty days.

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Potential subjects must agree to use acceptable contraception during their participation in this study.
Potential subjects must agree to avoid the following during their participation in this study:
participation in any other nicotine-related modification strategy outside of this protocol;
use of tobacco products other than cigarettes, including pipe tobacco, cigars, e-cigarettes, snuff, and chewing tobacco;
use of experimental (investigational) drugs or devices;
use of illegal drugs;
use of opiate medications.

Who cannot join

Inability to attend all required experimental sessions;
Presence of conditions that would make MRI unsafe (e.g. pacemaker);
Hypertension (systolic >140 mm Hg, diastolic >100 mm Hg, coupled with a history of hypertension); subjects with no previous diagnosis of hypertension may have a screening blood pressure up to 160/100.
Hypotension with symptoms (systolic <90 mm Hg, diastolic <60 mm Hg).
Coronary heart disease;
Lifetime history of heart attack;

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Cardiac rhythm disorder (irregular heart rhythm);
Chest pains (unless history, exam, and ECG clearly indicate a non-cardiac source);
Cardiac (heart) disorder (including but not limited to valvular heart disease, heart murmur, heart failure);
History of skin allergy;
Active skin disorder (e.g., psoriasis) within the last five years, except minor skin conditions (including but not limited to facial acne, minor localized infections, and superficial minor wounds);
Liver or kidney disorder (except kidney stones, gallstones);
Gastrointestinal problems or disease other than gastroesophageal reflux or heartburn;
Active ulcers in the past 30 days;
Lung disorder (including but not limited to Chronic obstructive pulmonary disease (COPD), emphysema, and asthma);
Brain abnormality (including but not limited to stroke, brain tumor, and seizure disorder);
Migraine headaches that occur more frequently than once per week;
Recent, unexplained fainting spells;
Problems giving blood samples;
Diabetes;
Current cancer or treatment for cancer in the past six months (except basal or squamous cell skin cancer);
Other major medical condition;
Current psychiatric disease (with the exception of anxiety disorders, Obsessive-compulsive disorder (OCD) and Attention deficit hyperactivity disorder (ADHD));
Bulimia or anorexia;
Suicidal ideation (within the past 10 years) or lifetime occurrence of attempted suicide;
Current depression;
Pregnant or nursing mothers;
Alcohol abuse;
Significant adverse reaction to nicotine patch, bupropion/Wellbutrin/Zyban or Chantix/Varenicline in the past.
Use (within the past 30 days) of:
Illegal drugs (or if the urine drug screen is positive);
Experimental (investigational) drugs;
Psychiatric medications including antidepressants, anti-psychotics or any other medications that are known to affect smoking cessation (e.g. clonidine);
Smokeless tobacco (chewing tobacco, snuff), cigars or pipes;
Nicotine replacement therapy or any other smoking cessation aid.
Use (within the past 14 days) of:
Opiate medications for pain or sleep (non-opiate medication for pain or sleep will be allowed).

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Duke Center for Nicotine and Smoking Cessation Research
Durham, North Carolina, 27705
Duke Center for Nicotine and Smoking Cessation Research
Raleigh, North Carolina, 27609

Other trials in United States

About this study

Conditions: Nicotine Dependence
Being tested: Varenicline, Bupropion, Nicotine patches, Placebo varenicline, Placebo bupropion
Keywords: Nicotine addiction, Cigarette smoking, Smoking cessation, Zyban, Chantix, Nicotine patches, varenicline, bupropion, fMRI
Medical subject headings: Tobacco Use Disorder, Cigarette Smoking, Smoking Cessation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

VareniclineDrug
Also called Chantix
BupropionDrug
Also called Zyban
Nicotine patchesDrug
Also called Nicoderm
Placebo vareniclineOther
Placebo bupropionOther
Placebo patchOther

Study groups in NCT01406223
Study group	Role	What they receive
varenicline	Active comparator	For the first 3 days after being switched from Nicotine Replacement Therapy (NRT) occurring at one week before the target quit date, smokers in this group will receive varenicline at a dose of 0.5 mg once per day followed by 0.5 mg twice a day for the remaining 4 days of that week. Subsequently, the dose will be 1 mg twice per day, and will remain at that dose for the remainder of the 12 weeks. During the time they receive varenicline, smokers in this group will also receive placebo bupropion and placebo patches. Receives: Drug: Varenicline; Drug: Nicotine patches; Other: Placebo bupropion; Other: Placebo patch
NRT (nicotine patches only)	Active comparator	21 mg/24 h for 2 weeks before the quit date and 7 weeks after the quit date, 14 mg/24 h for 2 weeks, and 7 mg/ 24 h for 2 weeks. After the 1st week, smokers in this group will also receive placebo bupropion and placebo varenicline. Receives: Drug: Nicotine patches; Other: Placebo varenicline; Other: Placebo bupropion
varenicline + bupropion	Active comparator	For the first 3 days after being switched from Nicotine Replacement Therapy (NRT) occurring at one week before the target quit date, smokers in this group will receive varenicline at a dose of 0.5 mg once per day followed by 0.5 mg twice a day for the remaining 4 days of that week plus bupropion at a dose of 150mg once per day. Subsequently, the dose of varenicline will be 1 mg twice per day and the dose of bupropion will be 150 mg twice per day, and will remain at that dose for the remainder of the 12 weeks. During the time they receive varenicline and bupropion, smokers in this group will also receive placebo patches. Receives: Drug: Varenicline; Drug: Bupropion; Drug: Nicotine patches; Other: Placebo patch
Post-quit NRT	Placebo comparator	Nicotine patches at 21 mg/24 h for 7 weeks after the quit date, 14 mg/24 h for 2 weeks, and 7 mg/ 24 h for 2 weeks. After the 1st week, smokers in this group will also receive placebo bupropion and placebo varenicline. Receives: Drug: Nicotine patches; Other: Placebo varenicline; Other: Placebo bupropion; Other: Placebo patch

What is being measured

The primary outcome is the main question the study is designed to answer.

The Amygdala, Anterior Insula, and Medial Prefrontal Cortex Scans Will be Compared to Evaluate Significant Differences
Mean blood-oxygen-level dependent (BOLD) contrast sensitive functional magnetic resonance imaging (fMRI) cue-reactivity signal following 2 week pre-quit treatment, controlling for baseline cue-reactivity.
Measured: change from baseline in whole brain blood-oxygen-level dependent (BOLD) contrast sensitive functional magnetic resonance imaging (fMRI) images collected during a cue-reactivity task following 2 weeks of pre-quit treatment

Secondary outcomes (1)

Days to First Cigarette Following Quitting Smoking
Days to first cigarette (i.e. lapse) will be measured via self-report.
Measured: Up to 11 weeks post quit day.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2011Jun 2014

First posted1 Aug 2011 (estimated)
Study startJul 2011
Primary completionDec 2013
Study completionJun 2014

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 Duke 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 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Care provider
Enrolment: 282 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01406223
Sponsor's protocol ID: Pro00028331
Other IDs: 1P50DA027840-01A1
Acronym: ConNicBrain
Status last verified: Oct 2017
First submitted: 12 Jun 2011
Last updated: 14 Nov 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
Young Adult Tobacco/Nicotine and Cannabis Co-use
Tobacco Use Disorder, Nicotine Dependence
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Social Media Support Groups for Adolescent Vaping Cessation
Vaping, Vaping Cessation
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The INITIATE Study: Initiating Nicotine Dependence Treatment for Smokers Admitted to Emergency Departments
Nicotine Dependence, Cigarettes, Nicotine Withdrawal
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All Nicotine Dependence trials

Study at a glance

From the registry record, last updated by the sponsor on 14 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Mechanistic Evaluations of Pre-Cessation Therapies for Smoking Cessation
ClinicalTrials.gov ID: NCT01406223
Acronym / sponsor ID: ConNicBrain / Pro00028331
Conditions: Nicotine Dependence
Keywords: Nicotine addiction, Cigarette smoking, Smoking cessation, Zyban, Chantix, Nicotine patches, varenicline, bupropion
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 282 participants (actual)
Lead sponsor: Duke UniversityUniversity, hospital or other
Collaborators: National Institute on Drug Abuse (NIDA)
Study start: Jul 2011
Primary completion: Dec 2013 (actual)
Study completion: Jun 2014 (actual)
First posted: 1 Aug 2011 (estimated)
Results: Posted 31 Aug 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, care provider)
Number of arms: 4

Arm	Type	Receives
varenicline	Active comparator	Drug: Varenicline, Drug: Nicotine patches, Other: Placebo bupropion, Other: Placebo patchFor the first 3 days after being switched from Nicotine Replacement Therapy (NRT) occurring at one week before the target quit date, smokers in this group will receive varenicline at a dose of 0.5 mg once per day followed by 0.5 mg twice a day for the remaining 4 days of that week. Subsequently, the dose will be 1 mg twice per day, and will remain at that dose for the remainder of the 12 weeks. During the time they receive varenicline, smokers in this group will also receive placebo bupropion and placebo patches.
NRT (nicotine patches only)	Active comparator	Drug: Nicotine patches, Other: Placebo varenicline, Other: Placebo bupropion21 mg/24 h for 2 weeks before the quit date and 7 weeks after the quit date, 14 mg/24 h for 2 weeks, and 7 mg/ 24 h for 2 weeks. After the 1st week, smokers in this group will also receive placebo bupropion and placebo varenicline.
varenicline + bupropion	Active comparator	Drug: Varenicline, Drug: Bupropion, Drug: Nicotine patches, Other: Placebo patchFor the first 3 days after being switched from Nicotine Replacement Therapy (NRT) occurring at one week before the target quit date, smokers in this group will receive varenicline at a dose of 0.5 mg once per day followed by 0.5 mg twice a day for the remaining 4 days of that week plus bupropion at a dose of 150mg once per day. Subsequently, the dose of varenicline will be 1 mg twice per day and the dose of bupropion will be 150 mg twice per day, and will remain at that dose for the remainder of the 12 weeks. During the time they receive varenicline and bupropion, smokers in this group will also receive placebo patches.
Post-quit NRT	Placebo comparator	Drug: Nicotine patches, Other: Placebo varenicline, Other: Placebo bupropion, Other: Placebo patchNicotine patches at 21 mg/24 h for 7 weeks after the quit date, 14 mg/24 h for 2 weeks, and 7 mg/ 24 h for 2 weeks. After the 1st week, smokers in this group will also receive placebo bupropion and placebo varenicline.

Who may qualify

Ages: 18 to 50 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (13 listed)

Are generally healthy;
Are 18-50 years old;
Smoke an average of at least 10 cigarettes per day for at least three cumulative years;
Have an afternoon expired air carbon monoxide (CO) reading of at least 10ppm;
Are right-handed as measured by a two-item scale used in our laboratory;

Key exclusion criteria (37 listed)

Inability to attend all required experimental sessions;
Presence of conditions that would make MRI unsafe (e.g. pacemaker);
Hypertension (systolic >140 mm Hg, diastolic >100 mm Hg, coupled with a history of hypertension); subjects with no previous diagnosis of hypertension may have a screening blood pressure up to 160/100.
Hypotension with symptoms (systolic <90 mm Hg, diastolic <60 mm Hg).
Coronary heart disease;

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
VareniclineAlso: Chantix	Drug	varenicline, varenicline + bupropion
BupropionAlso: Zyban	Drug	varenicline + bupropion
Nicotine patchesAlso: Nicoderm	Drug	NRT (nicotine patches only), Post-quit NRT, varenicline, varenicline + bupropion
Placebo varenicline	Other	NRT (nicotine patches only), Post-quit NRT
Placebo bupropion	Other	NRT (nicotine patches only), Post-quit NRT, varenicline
Placebo patch	Other	Post-quit NRT, varenicline, varenicline + bupropion

Primary outcome

The Amygdala, Anterior Insula, and Medial Prefrontal Cortex Scans Will be Compared to Evaluate Significant Differences
Time frame: change from baseline in whole brain blood-oxygen-level dependent (BOLD) contrast sensitive functional magnetic resonance imaging (fMRI) images collected during a cue-reactivity task following 2 weeks of pre-quit treatment
Mean blood-oxygen-level dependent (BOLD) contrast sensitive functional magnetic resonance imaging (fMRI) cue-reactivity signal following 2 week pre-quit treatment, controlling for baseline cue-reactivity.

1 secondary outcome

Days to First Cigarette Following Quitting Smoking
Time frame: Up to 11 weeks post quit day.

Results and safety

Results posted to the registry on 31 Aug 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Varenicline	18	6
NRT (Nicotine Patches Only)	19	7
Varenicline + Bupropion	20	2
Post-quit NRT	19	3

Primary outcome: The Amygdala, Anterior Insula, and Medial Prefrontal Cortex Scans Will be Compared to Evaluate Significant Differences

Time frame: change from baseline in whole brain blood-oxygen-level dependent (BOLD) contrast sensitive functional magnetic resonance imaging (fMRI) images collected during a cue-reactivity task following 2 weeks of pre-quit treatment. Mean (Standard Deviation). Unit: percent BOLD signal change

Measure	Varenicline n = 10	NRT (Nicotine Patches Only) n = 13	Varenicline + Bupropion n = 8	Post-quit NRT n = 8
left amygdala	0.057 (0.285)	.007 (.186)	.160 (.258)	.129 (.278)
right amydala	.051 (.337)	-.014 (.190)	.134 (.266)	.020 (.249)
left anterior insula	.094 (.196)	.013 (.244)	-.015 (.160)	.179 (.288)
right anterior insula	-.008 (.224)	.065 (.305)	.019 (.188)	.082 (.333)
left medial prefrontal cortex	.129 (.162)	.026 (.294)	-.120 (.562)	.009 (.200)
right medial prefrtonal cortex	.058 (.171)	-.010 (.277)	-.176 (.641)	-.017 (.178)

Population analysed: Only participants who completed both scanning sessions and provided useable data were included in imaging analysis.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Subjects were receiving study drugs for 13 weeks.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Varenicline	0 of 18 (0%)	3 of 18 (16.7%)	Not reported
NRT (Nicotine Patches Only)	0 of 19 (0%)	6 of 19 (31.6%)	Not reported
Varenicline + Bupropion	0 of 20 (0%)	6 of 20 (30%)	Not reported
Post-quit NRT	0 of 19 (0%)	4 of 19 (21.1%)	Not reported

Limitations and caveats (from the sponsor): Statistical comparisons of imaging data between groups are limited due to small sample size in each condition.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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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.

F. Joseph McClernon, Ph.D. principal investigator

Duke University

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Varenicline, Bupropion and Nicotine patches in people with Nicotine Dependence, run by Duke University 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 13 inclusion and 37 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 14 Nov 2017. 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. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 31 Aug 2017). 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?

The Amygdala, Anterior Insula, and Medial Prefrontal Cortex Scans Will be Compared to Evaluate Significant Differences (time frame: change from baseline in whole brain blood-oxygen-level dependent (BOLD) contrast sensitive functional magnetic resonance imaging (fMRI) images collected during a cue-reactivity task following 2 weeks of pre-quit treatment). 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 NCT01406223.

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 14 Nov 2017.