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Effects of rTMS on Cigarette Smoking and Cognition in Schizophrenia (rTMSsmokelab)

Primary Purpose

Schizophrenia, Nicotine Addiction

Status

Completed

Phase

Not Applicable

Locations

Canada

Study Type

Interventional

Intervention

Repetitive Transcranial Magnetic Stimulation (rTMS)

Sham Repetitive Transcranial Stimulation (rTMS)

About this trial

This is an interventional basic science trial for Schizophrenia focused on measuring Schizophrenia, Nicotine, Transcranial Magnetic Stimulation, Cognition, EEG

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria for all subjects:

Have a Full Scale IQ ≥ 80 as determined by the Shipley-2 which provides an estimate of pre-morbid intelligence
Be non-treatment seeking smokers;
Have a score greater than 5 on the Fagerstrom Test of Nicotine Dependence (FTND), a 5-item multiple choice questionnaire which assesses nicotine dependence
Report smoking of at least 10 cigarettes per day using a self-report 7-day timeline follow-back
Have an expired breath CO level >10ppm
Be able to provide informed consent.

Inclusion Criteria for Schizophrenia Subjects:

Meet SCID for DSM-IV diagnostic criteria for schizophrenia or schizoaffective disorder
Be in stable remission from positive symptoms of psychosis as judged by psychiatric evaluation and a PANSS total score <70
Be receiving a stable dose of antipsychotic mediation(s) for at least one month.

Inclusion Criteria for Healthy Controls:

Do not meet SCID for DSM-IV criteria for any current or past psychiatric disorder except for past major depression if it has been in remission for a minimum of one year
Not taking any psychotropic medications

General Exclusion Criteria:

Meet criteria for abuse or dependence of alcohol or illicit substances within the past 3 months (with the exception of nicotine dependence or caffeine)
Use of nicotine replacement or tobacco products other than cigarettes
Concomitant medical illness (including unstable or other presentations thought by investigators to compromise study participation, e.g. diabetes mellitus, hypothyroidism or acute/chronic renal insufficiency) or neurological illness including a history of seizures or a first-degree relative with a history of a seizure disorder
Be pregnant or planning to become pregnant
Metallic implants.

Sites / Locations

Centre for Addiction and Mental Health

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Repetitive Transcranial Magnetic Stimulation (rTMS)

Sham rTMS

Arm Description

Outcomes

Primary Outcome Measures

Cigarette craving as assessed by Tiffany Questionnaire for Smoking Urges (TQSU)

Craving will be assessed using the TQSU, a 32-item list of signs and symptoms of nicotine cravings and urges to smoke which subjects rate how strongly they agree or disagree with the statements on a scale of 1 (strongly disagree) to 7 (strongly agree).

Secondary Outcome Measures

Cigarette withdrawal using the Minnesota Nicotine Withdrawal Scale (MNWS)

Withdrawal will be assessed using the MNWS on which subjects self-report nicotine withdrawal symptoms including nicotine craving, irritability, anxiety, difficulty concentrating, restlessness, increased appetite or weight gain, depressed mood, and insomnia on a 5-point scale of 1 (none) to 5 (severe). Note: The internal consistencies and test-retest reliability of the MNWS, TQSU and FTND in schizophrenia are comparable to those observed in controls.

Expired breath carbon monoxide (CO) levels

Expired Breath CO (in parts per million; ppm) will be used to biochemically verify smoking status.

Plasma nicotine/cotinine levels

Plasma nicotine and cotinine levels will provide and objective measurement of cigarette smoking. Assays will be performed by the CAMH Clinical Laboratory using GC/MS/MS procedures which have been adapted from published procedures.

Continuous Performance Test-X (CPT-X)

The CPT-X is designed to measure sustained attention and response inhibition. Participants press the space bar as quickly as possible after each letter is presented except when the letter 'X' is presented. Common measures reported include % Hits, % Omissions, % Commissions, Reaction Time, Reactions Time Variability and an Attentional Index (d') Duration: 15 minutes

N-back

The N-back is designed to measure working memory (WM). This task requires continuous upgrades of the memory store and is suited to studying varying levels of working memory load. Task-load will be parametrically manipulated by varying the interval between targets requiring responses (i.e., 1-back, 3-back) according to previously published methods. The dependent variables of interest will include the average performance and reaction times. Duration:45 minutes.

Spatial Delayed Response (SDR)

The SDR is designed to measure visuospatial working memory (VSWM). Subjects focus on a central fixation cross on a computer screen. While fixated (staring at the cross), a dot-shaped cue flashes in one of 32 possible locations towards the outer edge of the screen. Then a delay period occurs (5, 15 or 30 seconds). After the delay, the fixation cross returns and the subjects must point on the computer screen where they remember seeing the dot cue. Results are reported as the averaged "distance from target" in cm for the 10 trials at each delay condition. Duration: 15 minutes.

EEG recording during performance of N-back Task

EEG recording during performance of N-back Task: EEG data will be collected using the methods reported in by our lab. A 64-electrode cap and Synamps2 DC-coupled EEG system (Compumedics) will be used. Evoked γ-power from the frontal electrodes will be measured while the participants complete the N-back task.

Hopkins Verbal Learning Test Revised (HVLT-R)

The HVLT measures verbal learning and memory. The HVLT-R is a verbal list-learning test designed to measure the acquisition of new verbal information using a 12-item word list.Duration: 10 minutes.

Smoking Topography

Smoking patterns will be assessed by measuring aspects of smoking topography (using the CReSS system) such as latency to puff, puff frequency, puff volume, puff duration, inter-puff interval, depth of inhalation and inter-cigarette interval which are postulated to be in vivo measures of smoking reinforcement.The CReSS calculates and stores a number of measures 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.

Spontaneous smoking

Spontaneous Smoking will be assessed by self-report using timeline followback (TLFB) methods.

Full Information

NCT ID

NCT01523730

First Posted

January 25, 2012

Last Updated

September 8, 2015

Sponsor

Centre for Addiction and Mental Health

Collaborators

Canadian Institutes of Health Research (CIHR)

1. Study Identification

Unique Protocol Identification Number

NCT01523730

Brief Title

Effects of rTMS on Cigarette Smoking and Cognition in Schizophrenia

Acronym

rTMSsmokelab

Official Title

Effects of Repetitive Transcranial Magnetic Stimulation on Cigarette Smoking and Cognitive Function in Smokers With and Without Schizophrenia

Study Type

Interventional

2. Study Status

Record Verification Date

September 2015

Overall Recruitment Status

Completed

Study Start Date

April 2012 (undefined)

Primary Completion Date

September 2015 (Actual)

Study Completion Date

September 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Centre for Addiction and Mental Health

Collaborators

Canadian Institutes of Health Research (CIHR)

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Cigarette smoking rates are extremely high in persons with schizophrenia and this increases the risk of disease and death due to tobacco-related disorders. One of the features of schizophrenia is reduced cognitive abilities, such as poor attention and memory. It is thought that people with schizophrenia smoke cigarettes to reduce these cognitive problems, as nicotine can improve cognitive function in these people. When people with schizophrenia stop smoking it causes further cognitive difficulties, which makes quitting harder for them compared to people without schizophrenia. A method called repetitive transcranial magnetic stimulation (rTMS) allows clinicians to give repeated magnetic pulses through the scalp to cause changes in brain activity and behaviour. rTMS can improve cognitive function in people with schizophrenia. Studies have also shown that rTMS can reduce tobacco craving and consumption of cigarettes. Therefore, we believe that rTMS will improve the cognitive deficits observed during cigarette smoking abstinence and help reduce cravings for cigarettes. Ultimately, rTMS may help smokers with schizophrenia who can't quit smoking with available treatments. This study will examine the effect of rTMS on tobacco cravings and cognitive problems produced by overnight abstinence from cigarette smoking in persons with schizophrenia in comparison to people without mental illness who smoke. Important information about the potential of rTMS for the treatment of cognitive deficits and tobacco addiction in schizophrenia will be obtained. Providing more effective smoking cessation treatments in people with schizophrenia may lead to improved physical and mental health for these patients, who are extremely susceptible to tobacco addiction and tobacco-related illness.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Schizophrenia, Nicotine Addiction

Keywords

Schizophrenia, Nicotine, Transcranial Magnetic Stimulation, Cognition, EEG

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

27 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Repetitive Transcranial Magnetic Stimulation (rTMS)

Arm Type

Active Comparator

Arm Title

Sham rTMS

Arm Type

Placebo Comparator

Intervention Type

Device

Intervention Name(s)

Repetitive Transcranial Magnetic Stimulation (rTMS)

Other Intervention Name(s)

Brain stimulation

Intervention Description

Subjects will undergo two testing weeks (active and sham rTMS treatment), washout period ≥ 1 month between the testing weeks. rTMS treatment sessions will take place twice daily on days 1-3 of each test week. Active treatment will be delivered at 90% resting motor threshold intensity. Stimulation will be administered at 20 Hz with 25 stimulation trains of 30 stimuli each with an inter-train interval of 30 sec at equivalent stimulation parameters as those used in our pilot trial. Stimulation Site: Advanced neuronavigation methods will be used to target rTMS to the dorsolateral prefrontal cortex following a T1 weighted MRI scan.

Intervention Type

Device

Intervention Name(s)

Sham Repetitive Transcranial Stimulation (rTMS)

Intervention Description

Subjects will undergo two testing weeks (active and sham rTMS treatment) administered in a randomized order, to which both experimenter and participant will be blind. There will be a washout period of at least one month between the testing weeks to ensure that any changes in cortical function induced by rTMS have returned to baseline. rTMS treatment sessions will take place twice daily on days 1-3 of each test week. Sham Condition: A single-wing tilt rTMS coil position producing somatic sensation (contraction of scalp muscles) with minimal direct brain effects will be used (same stimulation parameters and site as active condition).

Primary Outcome Measure Information:

Title

Cigarette craving as assessed by Tiffany Questionnaire for Smoking Urges (TQSU)

Description

Time Frame

Pre- and post rTMS/sham treatment week 1 and 2: at baseline smoking as usual (day 2), following over-night smoking abstinence (day 3am) and smoking reinstatement (day 3pm)

Secondary Outcome Measure Information:

Title

Cigarette withdrawal using the Minnesota Nicotine Withdrawal Scale (MNWS)

Description

Time Frame

Pre- and post rTMS/sham treatment week 1 and 2: at baseline smoking as usual (day 2), following over-night smoking abstinence (day 3am) and smoking reinstatement (day 3pm)

Title

Expired breath carbon monoxide (CO) levels

Description

Expired Breath CO (in parts per million; ppm) will be used to biochemically verify smoking status.

Time Frame

Pre- and post rTMS/sham treatment week 1 and 2: at baseline smoking as usual (day 1 and 2), following over-night smoking abstinence (day 3am) and smoking reinstatement (day 3pm)

Title

Plasma nicotine/cotinine levels

Description

Time Frame

Pre- and post rTMS/sham treatment week 1 and 2: at baseline smoking as usual (day 2), following over-night smoking abstinence (day 3am) and smoking reinstatement (day 3pm)

Title

Continuous Performance Test-X (CPT-X)

Description

Time Frame