Tobacco Use DisorderPhase 2NCT03497299
Combining rTMS With Varenicline to Prevent Smoking Lapse in Schizophrenia
A Phase 2 study testing Active rTMS (20Hz) in people with Tobacco Use Disorder and Schizophrenia, run by Centre for Addiction and Mental Health.
Trial summary
Tobacco smokers with schizophrenia are known to be resistant smokers, with high rates of smoking and inability to quit in the long-term, often related to smoking relapse. This may relate to problems with frontal lobe function associated with schizophrenia, which make these patients have great difficulty in dealing… Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Tobacco Use Disorder, Schizophrenia, Cognitive Functioning
- What is being tested?
- Active rTMS (20Hz)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Jul 2018to 31 Aug 2022
- Phase
- Phase 2
- 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 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- smokers with schizophrenia, non-treatment seeking (i.e., not trying to quit as indicated by <7 on the contemplation ladder)
- ages 18-55
- IQ ≥80 on the Weschler Test of Adult Reading
- Fagerstrom Test for Nicotine Dependence (FTND) ≥5
- smoke ≥ 10 cigarettes per day
- must meet SCID for DSM-5 diagnosis criteria for schizophrenia
- must be in stable remission from positive symptoms of psychosis as judged by a PANSS positive score total score <70
- must be receiving a stable dose of antipsychotics for >1month.
Who cannot join
- substance use (except nicotine or caffeine) in the last month
- a history of alcohol/drug abuse in the 3 months before study enrolment and use of opioids (e.g., meperidine, oxycodone, methadone)
- current use of smoking cessation aids (e.g., nicotine replacement therapy, bupropion or varenicline)
- pregnancy or nursing
- a history of renal insufficiency or a hypersensitivity to varenicline (Chantix®)
- a history of neurological illness like epilepsy or medical condition known to significantly influence neurocognitive function, at the discretion of the PI
- any other medical condition deemed relevant by the PI
About this study
Tobacco smokers with schizophrenia are known to be resistant smokers, with high rates of smoking and inability to quit in the long-term, often related to smoking relapse. This may relate to problems with frontal lobe function associated with schizophrenia, which make these patients have great difficulty in dealing with smoking withdrawal, urges and cravings. The current study will develop a combination approach that takes advantage of brain stimulation of the frontal lobes (repetitive transcranial magnetic stimulation (rTMS), in combination with the anti-smoking drug varenicline, to prevent smoking lapse using a well-established human laboratory method. Results from this study may have important implications for developing novel treatment approaches for smokers with schizophrenia.
Read the detailed description
Tobacco smokers with schizophrenia (SWS) represent a subset of smokers with high smoking prevalence compared to the general population, and reduced ability to quit smoking and to resist smoking relapse. There is some evidence that first-line treatments for tobacco use disorder are safe and effective for smoking cessation and smoking relapse-prevention in SWS, but these treatments do not appear to be as effective in smokers with a mental illness as compared to non-psychiatric tobacco smokers. Novel approaches to identify safe and effective treatments using human laboratory models may be an efficient strategy towards this important clinical goal.
The proposed human laboratory study will test the effects of standard pharmacotherapy for tobacco use disorder, the nicotinic partial agonist varenicline, in combination with an established brain stimulation method (repetitive transcranial magnetic stimulation;; rTMS) in SWS. This will allow for the determination of the benefits of combining rTMS with varenciline in SWS using a validated smoking lapse paradigm developed by the collaborator Sherry McKee, Ph.D. at Yale University. The present study represents a novel neuroscience-based strategy for targeting dorsolateral prefrontal cortex (DLPFC) dysfunction in schizophrenia, and is consistent with a target engagement and validation approach as endorsed by NIDA/NIH. Moreover, the subject population the investigators are targeting (SWS) are prone to quit attempt failures and rapid relapse to tobacco smoking, and are in need of novel and effective anti-smoking lapse interventions. The investigators' preliminary data support the use of the combination of varenicline and high-frequency (20 Hz) rTMS to target smoking lapse and craving outcomes in SWS. Accordingly, the investigators believe that the proposed goals, approach and implications for treatment development are substantial and likely to impact positively on clinical treatment research outcomes in this marginalized population of tobacco smokers. Specifically, using a randomized, double-blind, placebo-controlled parallel groups experimental design, the investigators will determine whether the combination of varenicline (2 mg/day) and high-frequency (20 Hz) rTMS versus varenicline and sham rTMS directed to the DLPFC will be superior for the prevention of tobacco smoking lapse behaviors in cigarette smokers with schizophrenia (N=80).
Hypothesis 1 (H1): Active (20 Hz) versus Sham rTMS will increase the time to smoking lapse in combination with varenicline in SWS.
Hypothesis 2 (H2): Active (20 Hz) versus Sham rTMS will improve prefrontal cognition in SWS, and this will be associated with increased ability to resist smoking lapse.
- Conditions
- Tobacco Use Disorder, Schizophrenia, Cognitive Functioning, Craving
- Being tested
- Active rTMS (20Hz), Sham rTMS
- Keywords
- Schizophrenia, Smoking, Lapse, Varenicline, Sham Repetitive Transcranial Magnetic Stimulation (rTMS)
- Medical subject headings
- Tobacco Use Disorder, Schizophrenia, Smoking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active rTMS (20Hz)Device
Repetitive Transcranial Magnetic Stimulation (rTMS) Procedures: On Day 1, participants will be randomly assigned to receive active or sham rTMS using the MagProX100/R30 stimulator equipped with the B65 active/ placebo coil for DLPFC stimulator (MagVenture, Farum, Denmark) for a period of 28 days.
Sham rTMSDevice
Repetitive Transcranial Magnetic Stimulation (rTMS) Procedures: On Day 1, participants will be randomly assigned to receive active or sham rTMS using the MagProX100/R30 stimulator equipped with the B65 active/ placebo coil for DLPFC stimulator (MagVenture, Farum, Denmark) for a period of 28 days.
| Study group | Role | What they receive |
|---|---|---|
| Active rTMS (20Hz) | Experimental | Active rTMS administered with the MagProX100/R30 stimulator equipped with the B65 active coil for dorsolateral prefrontal cortex (DLPFC) stimulator (MagVenture, Farum, Denmark).The randomization order will be determined by a project scientist from Temerty. While the primary aim of this study is not to treat individuals with tobacco dependence, it is imperative that participants attend weekly study visits in an attempt to achieve end of study (Day 28) tobacco abstinence. Receives: Device: Active rTMS (20Hz) |
| Sham rTMS | Sham comparator | Sham rTMS administered with the MagProX100/R30 stimulator equipped with the B65 placebo coil for DLPFC stimulator (MagVenture, Farum, Denmark). The randomization order will be determined by a project scientist from Temerty. While the primary aim of this study is not to treat individuals with tobacco dependence, it is imperative that participants attend weekly study visits in an attempt to achieve end of study (Day 28) tobacco abstinence. Receives: Device: Sham rTMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Smoking Lapse (TTL)
A measure of ability to resist smoking lapse during a 50 minute ad lib cigarette smoking period at Day 28 of the trial in SWS. Higher values indicate increased ability to resist smoking lapse.
Measured: Day 28
Secondary outcomes (2)
Smoking Topography
Using the Clinical Research Support System (CReSS), the investigators will assess smoking reinforcement outcomes including total number of puffs smoked per session, total puff volume per cigarette, puffs per cigarette, duration of inter--puff interval, average maximum puff velocity, average puff volume and average puff duration.
Measured: Day 28 (in comparison to baseline results at Day 0)
Spatial Delayed Response (SDR)/Visuospatial Working Memory (VSWM) Task
Subjects focus on a central fixation cross on a computer screen, a dot--shaped cue flashes towards the outer edge of the screen. A delay period then occurs, during which a series of shapes flash in the center of the screen;; the subjects must respond on the spacebar when the diamond shape appears. After the delay, which ranges from 5--30s to assess shorter-- vs. longer--term VSWM, the fixation cross returns and the subject must indicate where they remember seeing the dot. Results are reported as the averaged "distance from target" (cm) for the 16 trials at each delay condition. Duration: 15 minutes
Measured: Day 28 (in comparison to baseline results at Day 0)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2018
- Study start1 Jul 2018 (estimated)
- Primary completion31 Aug 2022 (estimated)
- Study completion31 Aug 2022 (estimated)
Why it stopped: lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Tobacco Use DisorderStudies of the same condition, open and under way.
- More trials run by Centre for Addiction and Mental HealthThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The study is a randomized controlled trial of active versus sham high frequency rTMS to the dorsolateral prefrontal cortex (DLPFC) in patients with schizophrenia who have co-occurring tobacco use disorder. The duration of treatment is 4 weeks and all subjects would receive open label Varenicline 2mg/day. The primary outcome measure is time to lapse to smoking.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre for Addiction and Mental Health
- Sponsor type
- University, hospital or other
- Collaborators
- Yale University, Oregon State University
- Responsible party
- Principal investigator, Tony George, Centre for Addiction and Mental Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03497299
- Sponsor's protocol ID
- 003-2017
- Status last verified
- Sep 2023
- First submitted
- 29 Mar 2018
- Last updated
- 6 Sep 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kozak K, Sharif-Razi M, Morozova M, Gaudette EV, Barr MS, Daskalakis ZJ, Blumberger DM, George TP. Effects of short-term, high-frequency repetitive transcranial magnetic stimulation to bilateral dorsolateral prefrontal cortex on smoking behavior and cognition in patients with schizophrenia and non-psychiatric controls. Schizophr Res. 2018 Jul;197:441-443. doi: 10.1016/j.schres.2018.02.015. Epub 2018 Feb 24.
PubMed 29486960Wing VC, Bacher I, Wu BS, Daskalakis ZJ, George TP. High frequency repetitive transcranial magnetic stimulation reduces tobacco craving in schizophrenia. Schizophr Res. 2012 Aug;139(1-3):264-6. doi: 10.1016/j.schres.2012.03.006. Epub 2012 Mar 29. No abstract available.
PubMed 22464727
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combining rTMS With Varenicline to Prevent Smoking Lapse in Schizophrenia
- ClinicalTrials.gov ID
- NCT03497299
- Acronym / sponsor ID
- 003-2017
- Conditions
- Tobacco Use Disorder, Schizophrenia, Cognitive Functioning, Craving
- Keywords
- Schizophrenia, Smoking, Lapse, Varenicline, Sham Repetitive Transcranial Magnetic Stimulation (rTMS)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: lack of funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Centre for Addiction and Mental HealthUniversity, hospital or other
- Collaborators
- Yale University, Oregon State University
- Study start
- 1 Jul 2018 (estimated)
- Primary completion
- 31 Aug 2022 (estimated)
- Study completion
- 31 Aug 2022 (estimated)
- First posted
- 13 Apr 2018 (actual)
- 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.
Tobacco smokers with schizophrenia are known to be resistant smokers, with high rates of smoking and inability to quit in the long-term, often related to smoking relapse. This may relate to problems with frontal lobe function associated with schizophrenia, which make these patients have great difficulty in dealing with smoking withdrawal, urges and cravings. The current study will develop a combination approach that takes advantage of brain stimulation of the frontal lobes (repetitive transcranial magnetic stimulation (rTMS), in combination with the anti-smoking drug varenicline, to prevent smoking lapse using a well-established human laboratory method. Results from this study may have important implications for developing novel treatment approaches for smokers with schizophrenia.
Detailed description
Tobacco smokers with schizophrenia (SWS) represent a subset of smokers with high smoking prevalence compared to the general population, and reduced ability to quit smoking and to resist smoking relapse. There is some evidence that first-line treatments for tobacco use disorder are safe and effective for smoking cessation and smoking relapse-prevention in SWS, but these treatments do not appear to be as effective in smokers with a mental illness as compared to non-psychiatric tobacco smokers. Novel approaches to identify safe and effective treatments using human laboratory models may be an efficient strategy towards this important clinical goal.
The proposed human laboratory study will test the effects of standard pharmacotherapy for tobacco use disorder, the nicotinic partial agonist varenicline, in combination with an established brain stimulation method (repetitive transcranial magnetic stimulation;; rTMS) in SWS. This will allow for the determination of the benefits of combining rTMS with varenciline in SWS using a validated smoking lapse paradigm developed by the collaborator Sherry McKee, Ph.D. at Yale University. The present study represents a novel neuroscience-based strategy for targeting dorsolateral prefrontal cortex (DLPFC) dysfunction in schizophrenia, and is consistent with a target engagement and validation approach as endorsed by NIDA/NIH. Moreover, the subject population the investigators are targeting (SWS) are prone to quit attempt failures and rapid relapse to tobacco smoking, and are in need of novel and effective anti-smoking lapse interventions. The investigators' preliminary data support the use of the combination of varenicline and high-frequency (20 Hz) rTMS to target smoking lapse and craving outcomes in SWS. Accordingly, the investigators believe that the proposed goals, approach and implications for treatment development are substantial and likely to impact positively on clinical treatment research outcomes in this marginalized population of tobacco smokers. Specifically, using a randomized, double-blind, placebo-controlled parallel groups experimental design, the investigators will determine whether the combination of varenicline (2 mg/day) and high-frequency (20 Hz) rTMS versus varenicline and sham rTMS directed to the DLPFC will be superior for the prevention of tobacco smoking lapse behaviors in cigarette smokers with schizophrenia (N=80).
Hypothesis 1 (H1): Active (20 Hz) versus Sham rTMS will increase the time to smoking lapse in combination with varenicline in SWS.
Hypothesis 2 (H2): Active (20 Hz) versus Sham rTMS will improve prefrontal cognition in SWS, and this will be associated with increased ability to resist smoking lapse.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- The study is a randomized controlled trial of active versus sham high frequency rTMS to the dorsolateral prefrontal cortex (DLPFC) in patients with schizophrenia who have co-occurring tobacco use disorder. The duration of treatment is 4 weeks and all subjects would receive open label Varenicline 2mg/day. The primary outcome measure is time to lapse to smoking.
| Arm | Type | Receives |
|---|---|---|
| Active rTMS (20Hz) | Experimental | Device: Active rTMS (20Hz)Active rTMS administered with the MagProX100/R30 stimulator equipped with the B65 active coil for dorsolateral prefrontal cortex (DLPFC) stimulator (MagVenture, Farum, Denmark).The randomization order will be determined by a project scientist from Temerty. While the primary aim of this study is not to treat individuals with tobacco dependence, it is imperative that participants attend weekly study visits in an attempt to achieve end of study (Day 28) tobacco abstinence. |
| Sham rTMS | Sham comparator | Device: Sham rTMSSham rTMS administered with the MagProX100/R30 stimulator equipped with the B65 placebo coil for DLPFC stimulator (MagVenture, Farum, Denmark). The randomization order will be determined by a project scientist from Temerty. While the primary aim of this study is not to treat individuals with tobacco dependence, it is imperative that participants attend weekly study visits in an attempt to achieve end of study (Day 28) tobacco abstinence. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- smokers with schizophrenia, non-treatment seeking (i.e., not trying to quit as indicated by <7 on the contemplation ladder)
- ages 18-55
- IQ ≥80 on the Weschler Test of Adult Reading
- Fagerstrom Test for Nicotine Dependence (FTND) ≥5
- smoke ≥ 10 cigarettes per day
Key exclusion criteria (7 listed)
- substance use (except nicotine or caffeine) in the last month
- a history of alcohol/drug abuse in the 3 months before study enrolment and use of opioids (e.g., meperidine, oxycodone, methadone)
- current use of smoking cessation aids (e.g., nicotine replacement therapy, bupropion or varenicline)
- pregnancy or nursing
- a history of renal insufficiency or a hypersensitivity to varenicline (Chantix®)
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 |
|---|---|---|
| Active rTMS (20Hz)Repetitive Transcranial Magnetic Stimulation (rTMS) Procedures: On Day 1, participants will be randomly assigned to receive active or sham rTMS using the MagProX100/R30 stimulator equipped with the B65 active/ placebo coil for DLPFC stimulator (MagVenture, Farum, Denmark) for a period of 28 days. | Device | Active rTMS (20Hz) |
| Sham rTMSRepetitive Transcranial Magnetic Stimulation (rTMS) Procedures: On Day 1, participants will be randomly assigned to receive active or sham rTMS using the MagProX100/R30 stimulator equipped with the B65 active/ placebo coil for DLPFC stimulator (MagVenture, Farum, Denmark) for a period of 28 days. | Device | Sham rTMS |
Primary outcome
Time to Smoking Lapse (TTL)
Time frame: Day 28
A measure of ability to resist smoking lapse during a 50 minute ad lib cigarette smoking period at Day 28 of the trial in SWS. Higher values indicate increased ability to resist smoking lapse.
2 secondary outcomes
Smoking Topography
Time frame: Day 28 (in comparison to baseline results at Day 0)
Spatial Delayed Response (SDR)/Visuospatial Working Memory (VSWM) Task
Time frame: Day 28 (in comparison to baseline results at Day 0)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Sep 2023.
- Results publication: PubMed 29486960Kozak K, Sharif-Razi M, Morozova M, Gaudette EV, Barr MS, Daskalakis ZJ, Blumberger DM, George TP. Effects of short-term, high-frequency repetitive transcranial magnetic stimulation to bilateral dorsolateral prefrontal cortex on smoking behavior and cognition in patients with schizophrenia and non-psychiatric controls. Schizophr Res. 2018 Jul;197:441-443. doi: 10.1016/j.schres.2018.02.015. Epub 2018 Feb 24.
- Results publication: PubMed 22464727Wing VC, Bacher I, Wu BS, Daskalakis ZJ, George TP. High frequency repetitive transcranial magnetic stimulation reduces tobacco craving in schizophrenia. Schizophr Res. 2012 Aug;139(1-3):264-6. doi: 10.1016/j.schres.2012.03.006. Epub 2012 Mar 29. No abstract available.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Active rTMS (20Hz) in people with Tobacco Use Disorder and Schizophrenia, run by Centre for Addiction and Mental Health.
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 8 inclusion and 7 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: withdrawn, as of the sponsor's last update on 6 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Time to Smoking Lapse (TTL) (time frame: Day 28). 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 NCT03497299, which also lists 2 linked publications.
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 6 Sep 2023.