Nicotine Dependence, CigarettesPhase 2NCT02723162
Translational Neuropsychopharmacology Research of Nicotine Addiction
A Phase 2 study testing Varenicline (VRN) and N-Acetylcysteine (NAC) in people with Nicotine Dependence, Cigarettes, run by Medical University of South Carolina at 1 site in United States.
Trial summary
This study will examine the effects of combining Varenicline (VRN) and N-acetylcysteine (NAC) on neural circuitry function and treating nicotine addiction. Healthy adult nicotine dependent cigarette smokers interested in quitting (n=110) will be randomized to one of four PBO-controlled conditions for 4 weeks: 1)… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Nicotine Dependence, Cigarettes
- What is being tested?
- Varenicline (VRN) and N-Acetylcysteine (NAC)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 67 participants
- Where
- 1 siteUnited States
- Study dates
- 4 May 2016to 9 Mar 2020
- Phase
- Phase 2
- 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
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age 18 - 55
- Right Handed
- English fluency
- 20/20 vision with corrective lenses.
- Smoke ≥ 10 cigarettes/day for a minimum of two years and have an expired carbon monoxide (CO) concentration of ≥ 10 ppm (to confirm inhalation).
- Interest in quitting smoking or contemplating a quit attempt in the next 6 months
- If female, agreement to use birth control
Who cannot join
- Past head injury or primary neurological disorder associated with MRI abnormalities, including dementia, MCI, brain tumors, epilepsy, Parkinson's disease, or demyelinating diseases
- Any physical or intellectual disability affecting completion of assessments
- Any contraindication to MRI
- Positive urine drug screen for illicit substances (such as marijuana or cocaine).
- Current or past psychosis
- Electroconvulsive therapy in last 6 months
- Use of antidepressant medications or other psychotropic medications in the last month.
- Positive urine pregnancy test or current breast feeding status
Trial locations and contacts
1 site in 1 country.
United States1 site
Medical University of South Carolina
Charleston, South Carolina, 29403
About this study
This study will examine the effects of combining Varenicline (VRN) and N-acetylcysteine (NAC) on neural circuitry function and treating nicotine addiction. Healthy adult nicotine dependent cigarette smokers interested in quitting (n=110) will be randomized to one of four PBO-controlled conditions for 4 weeks: 1) VRN+NAC, 2) VRN+PBO, 3) NAC+PBO or 4) PBO+PBO. Following 1 week of medication, participants will be contingently reinforced for 3 days of smoking abstinence and be scanned using functional magnetic resonance imaging (fMRI) techniques, while nicotine deprived during a resting state and a cue-reactivity (CR) task. Participants will be followed over the next 3 weeks of treatment and clinical variables will be assessed.
Read the detailed description
Cigarette (henceforth nicotine) addiction is a chronic, relapsing brain disorder and remains the leading preventable cause of death and disability in the US, costing nearly $200 billion each year. Although ~20% of adults in the USA currently smoke, the majority want to quit. In spite of the breadth of research focused on improving health outcomes and reducing the societal burden caused by nicotine addiction, the majority of smokers who attempt to quit will relapse. Nicotine withdrawal-related disturbances in executive function, negative affect and reward processes compel a smoker to self-administer nicotine-each in turn representing the loss of control to remain abstinent and risk factors for relapse. Thus, identifying the effects of nicotine addiction on mechanisms of self-regulation, and the value of novel medications for remediating dysregulated behavior are both needed in order to enhance interventions for treating nicotine addiction. The preliminary data, along with the extant literature, suggest that the maintenance of nicotine addiction is subserved by dysregulated neural function in limbic-striatal and corticostriatal neural circuitry. While VRN may be effective in treating limbic-striatal circuitry that is associated with promoting abstinence and reducing acute withdrawal; NAC may be effective in treating corticostriatal circuitry function that is associated with relapse vulnerability. Thus, the current proposal seeks to investigate two medications (VRN \& NAC), with potentially complementary effects on the two different brain circuits- limbic-striatal (VRN) and corticostriatal (NAC) circuitry-and that may therapeutically target two different phases in the recovery of nicotine addiction-the promotion of abstinence (VRN) and relapse prevention (NAC). The placebo (PBO)-controlled design in this proposal will allow the team to identify and translate between the neurobiological substrates and the neurocognitive underpinnings of the effects of VRN+NAC on smoking behavior in humans-thus, advancing the understanding of the pathophysiology of nicotine addiction.
- Conditions
- Nicotine Dependence, Cigarettes
- Being tested
- Varenicline (VRN), N-Acetylcysteine (NAC), Placebo
- Medical subject headings
- Tobacco Use Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Varenicline (VRN)Drug
VRN will be provided at the standard recommended dose (0.5 mg daily for 3 days, then 0.5 mg twice daily for 4 days, then 1 mg twice daily thereafter for the remaining 21 days of active treatment.
N-Acetylcysteine (NAC)Drug
NAC will be dosed at 1200 mg twice daily throughout the 28-day active treatment
PlaceboDrug
Matched placebo
| Study group | Role | What they receive |
|---|---|---|
| VRN+ NAC | Experimental | Titrated VRN up to 1mg BID with NAC at 1200mg BID for 28 days Receives: Drug: Varenicline (VRN); Drug: N-Acetylcysteine (NAC) |
| NAC+ PBO | Active comparator | 1200mg BID for 28 days plus VRN placebo for 28 days Receives: Drug: N-Acetylcysteine (NAC); Drug: Placebo |
| VRN+ PBO | Active comparator | Titrated VRN up to 1mg BID with NAC placebo for 28 days Receives: Drug: Varenicline (VRN); Drug: Placebo |
| PBO+PBO | Placebo comparator | Double placebo taken for 28 days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in Blood Oxygen Level Dependent (BOLD) Signal Response
Measure the Effects of Varenicline and N-Acetylcysteine (NAC) on brain activation to smoking images while participants undergo Functional Magnetic Resonance (fMRI) Imaging. Mean percent signal change of fMRI BOLD in the insula and nucleus accumbens will be recorded during smoking images. The lower the BOLD signal response, the better the outcome, meaning reduced reactivity to smoking images.
Measured: 10 Days
rZ Change Score in Resting State Functional Connectivity From Baseline
Measure the effects of Varenicline and N-Acetylcysteine on resting-state functional connectivity while participants undergo fMRI. Fisher transformed correlation (rZ) scores will be recorded between medial prefrontal cortex and ventral striatum during a resting state scan. The higher the rZ score, the better the outcome, meaning stronger functional connectivity. rZ scores range from -1 to 1. The rZ-score central value is analogous to a central value to of a Z-score of 0, representing the population mean.
Measured: Baseline to day 10
Secondary outcomes (1)
Number of Cigarettes Smoked Per Day
Measure the effects of Varenicline and N-Acetylcysteine on smoking behavior over the course of the study
Measured: 28 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2016 (estimated)
- Study start4 May 2016
- Primary completion9 Mar 2020
- Study completion9 Mar 2020
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 Dependence, CigarettesStudies of the same condition, open and under way.
- More trials run by Medical University of South CarolinaThe 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 2
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of South Carolina
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kevin Gray, MD, Medical University of South Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02723162
- Sponsor's protocol ID
- PRO#48152
- Status last verified
- Jul 2022
- First submitted
- 7 Mar 2016
- Last updated
- 18 Aug 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Translational Neuropsychopharmacology Research of Nicotine Addiction
- ClinicalTrials.gov ID
- NCT02723162
- Acronym / sponsor ID
- PRO#48152
- Conditions
- Nicotine Dependence, Cigarettes
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- Medical University of South CarolinaUniversity, hospital or other
- Study start
- 4 May 2016 (actual)
- Primary completion
- 9 Mar 2020 (actual)
- Study completion
- 9 Mar 2020 (actual)
- First posted
- 30 Mar 2016 (estimated)
- Results
- Posted 18 Aug 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will examine the effects of combining Varenicline (VRN) and N-acetylcysteine (NAC) on neural circuitry function and treating nicotine addiction. Healthy adult nicotine dependent cigarette smokers interested in quitting (n=110) will be randomized to one of four PBO-controlled conditions for 4 weeks: 1) VRN+NAC, 2) VRN+PBO, 3) NAC+PBO or 4) PBO+PBO. Following 1 week of medication, participants will be contingently reinforced for 3 days of smoking abstinence and be scanned using functional magnetic resonance imaging (fMRI) techniques, while nicotine deprived during a resting state and a cue-reactivity (CR) task. Participants will be followed over the next 3 weeks of treatment and clinical variables will be assessed.
Detailed description
Cigarette (henceforth nicotine) addiction is a chronic, relapsing brain disorder and remains the leading preventable cause of death and disability in the US, costing nearly $200 billion each year. Although ~20% of adults in the USA currently smoke, the majority want to quit. In spite of the breadth of research focused on improving health outcomes and reducing the societal burden caused by nicotine addiction, the majority of smokers who attempt to quit will relapse. Nicotine withdrawal-related disturbances in executive function, negative affect and reward processes compel a smoker to self-administer nicotine-each in turn representing the loss of control to remain abstinent and risk factors for relapse. Thus, identifying the effects of nicotine addiction on mechanisms of self-regulation, and the value of novel medications for remediating dysregulated behavior are both needed in order to enhance interventions for treating nicotine addiction. The preliminary data, along with the extant literature, suggest that the maintenance of nicotine addiction is subserved by dysregulated neural function in limbic-striatal and corticostriatal neural circuitry. While VRN may be effective in treating limbic-striatal circuitry that is associated with promoting abstinence and reducing acute withdrawal; NAC may be effective in treating corticostriatal circuitry function that is associated with relapse vulnerability. Thus, the current proposal seeks to investigate two medications (VRN \& NAC), with potentially complementary effects on the two different brain circuits- limbic-striatal (VRN) and corticostriatal (NAC) circuitry-and that may therapeutically target two different phases in the recovery of nicotine addiction-the promotion of abstinence (VRN) and relapse prevention (NAC). The placebo (PBO)-controlled design in this proposal will allow the team to identify and translate between the neurobiological substrates and the neurocognitive underpinnings of the effects of VRN+NAC on smoking behavior in humans-thus, advancing the understanding of the pathophysiology of nicotine addiction.
Study design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| VRN+ NAC | Experimental | Drug: Varenicline (VRN), Drug: N-Acetylcysteine (NAC)Titrated VRN up to 1mg BID with NAC at 1200mg BID for 28 days |
| NAC+ PBO | Active comparator | Drug: N-Acetylcysteine (NAC), Drug: Placebo1200mg BID for 28 days plus VRN placebo for 28 days |
| VRN+ PBO | Active comparator | Drug: Varenicline (VRN), Drug: PlaceboTitrated VRN up to 1mg BID with NAC placebo for 28 days |
| PBO+PBO | Placebo comparator | Drug: PlaceboDouble placebo taken for 28 days |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Age 18 - 55
- Right Handed
- English fluency
- 20/20 vision with corrective lenses.
- Smoke ≥ 10 cigarettes/day for a minimum of two years and have an expired carbon monoxide (CO) concentration of ≥ 10 ppm (to confirm inhalation).
Key exclusion criteria (8 listed)
- Past head injury or primary neurological disorder associated with MRI abnormalities, including dementia, MCI, brain tumors, epilepsy, Parkinson's disease, or demyelinating diseases
- Any physical or intellectual disability affecting completion of assessments
- Any contraindication to MRI
- Positive urine drug screen for illicit substances (such as marijuana or cocaine).
- Current or past psychosis
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 |
|---|---|---|
| Varenicline (VRN)VRN will be provided at the standard recommended dose (0.5 mg daily for 3 days, then 0.5 mg twice daily for 4 days, then 1 mg twice daily thereafter for the remaining 21 days of active treatment. | Drug | VRN+ NAC, VRN+ PBO |
| N-Acetylcysteine (NAC)NAC will be dosed at 1200 mg twice daily throughout the 28-day active treatment | Drug | NAC+ PBO, VRN+ NAC |
| PlaceboMatched placebo | Drug | NAC+ PBO, PBO+PBO, VRN+ PBO |
Primary outcome
Percent Change in Blood Oxygen Level Dependent (BOLD) Signal Response
Time frame: 10 Days
Measure the Effects of Varenicline and N-Acetylcysteine (NAC) on brain activation to smoking images while participants undergo Functional Magnetic Resonance (fMRI) Imaging. Mean percent signal change of fMRI BOLD in the insula and nucleus accumbens will be recorded during smoking images. The lower the BOLD signal response, the better the outcome, meaning reduced reactivity to smoking images.
rZ Change Score in Resting State Functional Connectivity From Baseline
Time frame: Baseline to day 10
Measure the effects of Varenicline and N-Acetylcysteine on resting-state functional connectivity while participants undergo fMRI. Fisher transformed correlation (rZ) scores will be recorded between medial prefrontal cortex and ventral striatum during a resting state scan. The higher the rZ score, the better the outcome, meaning stronger functional connectivity. rZ scores range from -1 to 1. The rZ-score central value is analogous to a central value to of a Z-score of 0, representing the population mean.
1 secondary outcome
Number of Cigarettes Smoked Per Day
Time frame: 28 Days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2022.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Varenicline (VRN) and N-Acetylcysteine (NAC) in people with Nicotine Dependence, Cigarettes, run by Medical University of South Carolina 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 7 inclusion and 8 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 18 Aug 2022. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 18 Aug 2022). 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?
Percent Change in Blood Oxygen Level Dependent (BOLD) Signal Response (time frame: 10 Days). 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?
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 18 Aug 2022; AzTrials last refreshed its copy on 8 Nov 2026.