Circuitry-Guided Smoking Cessation in Schizophrenia

Schizophrenia Clinical Trial

Official title:

Circuitry-Guided Smoking Cessation in Schizophrenia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03281629
• Other study ID #: HP-00077085
• Secondary ID: UG3DA047685
• Status: Completed
• Phase: N/A
• Start date: October 19, 2018
• Est. completion date: February 15, 2022

Study information

• Verified date: December 2022
• Source: University of Maryland, Baltimore
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: February 15, 2022
• Est. primary completion date: February 28, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

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).

Related Conditions & MeSH terms

• Nicotine Addiction
• Schizophrenia
• Smoking Cessation
• Tobacco Use Disorder

Intervention

Device:
• Active TMS stimulation
Multiple trains of active transcranial magnetic stimulation in a day, for multiple days.
• Sham TMS stimulation
Multiple trains of sham transcranial magnetic stimulation in a day, for multiple days.

Locations

Country	Name	City	State
United States	University of Maryland, Baltimore	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
University of Maryland, Baltimore	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cigarette Per Day	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.	7 months
Secondary	Functional Magnetic Resonance Imaging (fMRI)	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).	4 months
Secondary	Cotinine	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).	1 month
Secondary	End-expired Carbon Monoxide (CO)	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).	1 month
Secondary	Normalized Gamma Power of Auditory Static State Response (ASSR) From Electroencephalography (EEG)	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).	4 months