Circuitry-Guided Smoking Cessation in Schizophrenia (UH3)

Study Overview
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Brief Summary
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Patients with schizophrenia spectrum disorder (SSD) will be exposed to active repetitive transcranial magnetic stimulation (rTMS) from F8 coil or active rTMS from H coil for smoking cessation. Smoking and brain functional connectivity changes will be assessed at baseline, different stages of rTMS and/or follow-ups.

Detailed Description
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Neuroimaging studies suggest that high rate of smoking in patients with schizophrenia may be due to an overlap of nicotine addiction-related circuitries and schizophrenia-related circuitries, such that schizophrenia impacts some of the same circuitries that increase risks for severe nicotine addiction in general. Those identified overlapping circuitries have been linked to several key features of nicotine addiction and can be represented by resting-state functional connectivities. The investigators aim to develop a TMS method targeting special brain circuits that are both smoking cessation and schizophrenia-related. If the corresponding brain circuits were successfully modulated, the treatment efficacy will be significantly improved and schizophrenia patients will benefit from the TMS treatment of smoking cessation. The F8 coil based rTMS is not FDA approved for smoking cessation at this point, the rTMS with H4 coil is FDA-cleared for short-term smoking cessation in the general population, its efficacy in SSD has not been evaluated. In this protocol, the investigators will compare them in patients with schizophrenia spectrum disorders.

Official Title
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Circuitry-Guided Smoking Cessation in Schizophrenia (UH3)

Conditions
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Smoking Cessation, Nicotine Addiction, Schizophrenia

Intervention / Treatment
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* Device: active F8-coil delivered rTMS
* Device: active H-coil delivered rTMS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female between ages 18-60 Ability to give written informed consent Smoking in the last one year or more and average cigarette per day ≥ 5 in the past 4 weeks. Diagnosed with schizophrenia-spectrum disorder and Evaluation to Sign Consent (ESC) above10. Exclusion Criteria: Any history of seizures. Had smoking cessation treatment, clinical trial, or nicotine replacements within the past four weeks. Significant alcohol or other drug use (substance dependence within 6 months or substance abuse within 1 month) other than nicotine or marijuana dependence. Any major medical illnesses that may affect normal brain functioning. Examples of these conditions include, but not limited to, stroke, CNS infection or tumor, other significant brain neurological conditions. Taking > 400 mg clozapine/day or Failed TMS screening questionnaire. Cardiac pacemakers, implanted medication pumps, intracardiac lines, or acute, unstable cardiac disease, with intracranial implants (e.g. aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed. History of head injury with loss of consciousness over 10 minutes; history of brain surgery. Can not refrain from using alcohol and/or marijuana 24 hours or more & cigarette smoking one hour or more prior to experiments. Woman who is pregnant (child-bearing potential but not on contraceptive and missing menstrual period; or by self report; or by positive pregnancy test) or has had unprotected sexual intercourse without birth control in the last 4 weeks. Have active suicidal ideation and behavior.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study group<br>Participants in this group will receive active F8-coil delivered rTMS. | Device: active F8-coil delivered rTMS<br>* Multiple trains of rTMS in a day, for multiple days.<br>|
| Active Comparator: Active control group<br>Participants in this group will receive active H-coil delivered rTMS. | Device: active H-coil delivered rTMS<br>* Multiple trains of rTMS in a day, for multiple days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resting-state functional connectivity (rsFC) from functional magnetic resonance imaging (fMRI) | The strength of rsFC from fMRI is used to represent the brain activities that are corresponding to the TMS effect on smoking reduction/cessation. | 1 month | 
| Cigarette per day | Cigarette per day (CPD) is measured to index smoking reduction and cessation. | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fagerstrom Test for Nicotine Dependence (FTND) | Fagerstrom Test for Nicotine Dependence (FTND) represents the severity of nicotine severity. | 1 month | 
| nicotine/creatinine | nicotine/creatinine is a index of smoking status. | 1 month | 
| End-expired carbon monoxide (CO) | End-expired CO measure is an instant measure of smoking status. | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transcranial magnetic stimulation, schizophrenia, smoking, nicotine, tobacco