Back to resultsCircuitry-Guided Smoking Cessation in Schizophrenia
Primary Purpose
Smoking Cessation, Nicotine Addiction, Schizophrenia
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Active TMS stimulation
Sham TMS stimulation
Sponsored by
About this trial
This is an interventional other trial for Smoking Cessation focused on measuring Transcranial magnetic stimulation, schizophrenia, MRI, smoking
Eligibility Criteria
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).
Sites / Locations
- University of Maryland, Baltimore
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Sham Comparator
Arm Label
Active TMS stimulation
Sham TMS stimulation
Arm Description
Real active rTMS stimulation.
Sham repetitive TMS stimulation.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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).
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).
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).
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).
Full Information
NCT ID
NCT03281629
First Posted
September 1, 2017
Last Updated
December 21, 2022
Sponsor
University of Maryland, Baltimore
Collaborators
National Institute on Drug Abuse (NIDA)
1. Study Identification
Unique Protocol Identification Number
NCT03281629
Brief Title
Circuitry-Guided Smoking Cessation in Schizophrenia
Official Title
Circuitry-Guided Smoking Cessation in Schizophrenia
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Completed
Study Start Date
October 19, 2018 (Actual)
Primary Completion Date
February 28, 2021 (Actual)
Study Completion Date
February 15, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Maryland, Baltimore
Collaborators
National Institute on Drug Abuse (NIDA)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Smoking Cessation, Nicotine Addiction, Schizophrenia
Keywords
Transcranial magnetic stimulation, schizophrenia, MRI, smoking
7. Study Design
Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
44 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Active TMS stimulation
Arm Type
Active Comparator
Arm Description
Real active rTMS stimulation.
Arm Title
Sham TMS stimulation
Arm Type
Sham Comparator
Arm Description
Sham repetitive TMS stimulation.
Intervention Type
Device
Intervention Name(s)
Active TMS stimulation
Intervention Description
Multiple trains of active transcranial magnetic stimulation in a day, for multiple days.
Intervention Type
Device
Intervention Name(s)
Sham TMS stimulation
Intervention Description
Multiple trains of sham transcranial magnetic stimulation in a day, for multiple days.
Primary Outcome Measure Information:
Title
Cigarette Per Day
Description
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.
Time Frame
7 months
Secondary Outcome Measure Information:
Title
Functional Magnetic Resonance Imaging (fMRI)
Description
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).
Time Frame
4 months
Title
Cotinine
Description
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).
Time Frame
1 month
Title
End-expired Carbon Monoxide (CO)
Description
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).
Time Frame
1 month
Title
Normalized Gamma Power of Auditory Static State Response (ASSR) From Electroencephalography (EEG)
Description
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).
Time Frame
4 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xiaoming Du, MD
Organizational Affiliation
University of Maryland, Baltimore
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Maryland, Baltimore
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21228
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Circuitry-Guided Smoking Cessation in Schizophrenia
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