A Phase 2 interventional study of Active rTMS (20Hz) and Sham rTMS in Tobacco Use Disorder, Schizophrenia and Cognitive Functioning, sponsored by Centre for Addiction and Mental Health. Withdrawn. Open to participants aged 18 Years to 55 Years. Per ClinicalTrials.gov, last updated 2023-09-06.
Sponsored by Centre for Addiction and Mental Health · Phase 2, Interventional, and Treatment
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.
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.
Exclusion Criteria:
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.
Device: Active rTMS (20Hz)
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.
Device: Sham rTMS
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.
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.
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.
Time frame: Day 28
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.
Time frame: 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
Time frame: Day 28 (in comparison to baseline results at Day 0)
No study locations are listed for this record.
Plan to share: No
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Centre for Addiction and Mental Health