Circuitry-Guided Smoking Cessation in Schizophrenia

Not Applicable

Completed

• Conditions: Smoking Cessation; Nicotine Addiction; Schizophrenia
• Interventions: Device: Sham TMS stimulation; Device: Active TMS stimulation

• Registration Number: NCT03281629
• Lead Sponsor: University of Maryland, Baltimore

Brief Summary

In a double-blinded, randomized, parallel controlled design, patients with schizophrenia spectrum disorder will be exposed to active or sham repetitive transcranial magentic stimulation (TMS) which was guided by functional magnetic resonance image (MRI). Smoking reduction/cessation and brain functional connectivity changes will be assessed at baseline, different stages of rTMS and/or follow-ups.

Detailed Description

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 impact 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. Transcranial magnetic stimulation (TMS) provides a non-invasive means for altering brain electrical neural activity. TMS has been approved by FDA for treatment of depression. Other applications have not been approved but it has been used in a wide range of clinical research especially in neurology and psychiatry. There are preliminarily significant improvements in treatments of smoking cessation in schizophrenia using TMS with small samples, but those treatments are not robust in larger samples. The high inter-subject variability limits the efficacy of TMS treatment in schizophrenia patients. We 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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2017-09-01
• Study First Submitted QC: 2017-09-11
• Study First Posted: 2017-09-13
• Study Start: 2018-10-19
• Primary Completion: 2021-02-28
• Study Completion: 2022-02-15
• Results First Submitted: 2022-09-23
• Status Verified: 2022-12
• Results First Submitted QC: 2022-12-21
• Last Update Submitted: 2022-12-21
• Results First Posted: 2023-01-18
• Last Update Posted: 2023-01-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 44

Inclusion Criteria

• Male and female between ages 18-60
• Ability to give written informed consent (age 18 or above)
• Smoking in the last one year or more and average cigarette per day ≥ 5 in the past 4 weeks.
• For patient participants, Evaluation to Sign Consent (ESC) above10.

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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
• 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).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sham TMS stimulation	Sham TMS stimulation	Sham repetitive TMS stimulation.
Active TMS stimulation	Active TMS stimulation	Real active rTMS stimulation.

Primary Outcome Measures

Name	Time	Method
Cigarette Per Day	7 months	Cigarette per day (CPD) is measured to index smoking reduction and cessation. The change of CPD between baseline and end-of-treatment (1-month time point), 3-month follow up (4-month time point) and 6-month follow up (7-month time point) are reported. Negative values of the change of CPD indicate reductions in cigarette consumption.

Secondary Outcome Measures

Name	Time	Method
Functional Magnetic Resonance Imaging (fMRI)	4 months	Resting-state functional connectivity (rsFC) obtained from fMRI is used to evaluate the TMS effect on smoking cessation. The strength of rsFC was first defined by correlation coefficient (r). Because the distribution of r values is highly skewed, z scores (normally distributed) were computed via fisher r-to-z transform. The z score central value (i.e., z score of 0) represents no relationship between the two brain regions. A positive (negative) z score indicates a positive (negative) association between the two brain regions. According to our pilot data determined from a separate study, stronger rsFC (i.e., larger positive z score) was related to less smoking severity. The changes of rsFC between baseline and end-of-treatment (1-month time point) and 3-month follow up (4-month time point) are reported. A positive (negative) value of rsFC change suggests the rsFC was enhanced (weakened) by the intervention. No fMRI data were collected at 6-month follow up (7-month time point).
Cotinine	1 month	Cotinine level is an objective index of smoking status. Higher level of cotinine indicates more nicotine consumption. The change of cotinine level between baseline and end-of-treatment (1-month time point) is reported. Cotinine data were not collected at 3-month follow up (4-month time point) or 6-month follow up (7-month time point).
End-expired Carbon Monoxide (CO)	1 month	End-expired CO measure is an instant measure of smoking status. Higher CO level indicates more nicotine consumption. The change of CO level between baseline and end-of-treatment (1-month time point) is reported. No CO data were collected at 3-month follow up (4-month time point) or 6-month follow up (7-month time point).
Normalized Gamma Power of Auditory Static State Response (ASSR) From Electroencephalography (EEG)	4 months	EEG is used to evaluate the brain activities that are corresponding to the TMS. Auditory static state response (ASSR) at gamma frequency (i.e., 40 Hz) is obtained from the EEG recording. The gamma power of ASSR was normalized as the ratio between the power at 40 Hz (i.e., gamma power) and the power of its neighboring frequencies (i.e., 39 and 41 Hz). Increased normalized gamma ASSR is usually related to the improvement of psychosis symptoms. The change of ASSR between baseline and end-of-treatment (1-month time point) and 3-month follow up (4-month time point) are reported. No EEG data were collected at 6-month follow up (7-month time point).

Trial Locations

Locations (1)

University of Maryland, Baltimore; 🇺🇸 Baltimore, Maryland, United States