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

This study is currently recruiting participants.
Verified March 2014 by Centre for Addiction and Mental Health
Sponsor:
Collaborator:
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Tony George, Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier:
NCT01523730
First received: January 25, 2012
Last updated: March 17, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention
Schizophrenia
Nicotine Addiction
Device: Repetitive Transcranial Magnetic Stimulation (rTMS)
Device: Sham Repetitive Transcranial Stimulation (rTMS)

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Effects of Repetitive Transcranial Magnetic Stimulation on Cigarette Smoking and Cognitive Function in Smokers With and Without Schizophrenia

Resource links provided by NLM:


Further study details as provided by Centre for Addiction and Mental Health:

Primary Outcome Measures:
  • Cigarette craving as assessed by Tiffany Questionnaire for Smoking Urges (TQSU) [ 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) ] [ Designated as safety issue: No ]
    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) [ 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) ] [ Designated as safety issue: No ]
    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 [ 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) ] [ Designated as safety issue: No ]
    Expired Breath CO (in parts per million; ppm) will be used to biochemically verify smoking status.

  • Plasma nicotine/cotinine levels [ 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) ] [ Designated as safety issue: No ]
    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) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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 [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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 [ Time Frame: 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) ] [ Designated as safety issue: No ]

    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) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 1 and 2: At baseline, day 2 when smoking as usual and following over-night smoking abstinence day 3 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 1 and 2: Pre- and post rTMS/sham treatment at baseline day 1 and 2 when smoking as usual) and following over-night smoking abstinence day 3 ] [ Designated as safety issue: No ]
    Spontaneous Smoking will be assessed by self-report using timeline followback (TLFB) methods.


Estimated Enrollment: 50
Study Start Date: April 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Repetitive Transcranial Magnetic Stimulation (rTMS) Device: Repetitive Transcranial Magnetic Stimulation (rTMS)
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.
Other Name: Brain stimulation
Placebo Comparator: Sham rTMS Device: Sham Repetitive Transcranial Stimulation (rTMS)
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).

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria for all subjects:

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

Inclusion Criteria for Schizophrenia Subjects:

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

Inclusion Criteria for Healthy Controls:

  1. 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
  2. Not taking any psychotropic medications

General Exclusion Criteria:

  1. Meet criteria for abuse or dependence of alcohol or illicit substances within the past 3 months (with the exception of nicotine dependence or caffeine)
  2. Use of nicotine replacement or tobacco products other than cigarettes
  3. 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
  4. Be pregnant or planning to become pregnant
  5. Metallic implants.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01523730

Contacts
Contact: Mera Barr, Ph.D. 416-5358501 ext 33095 mera.barr@camh.ca
Contact: Tony P George, M.D. 416-5358501 ext 4544 tony.george@camh.ca

Locations
Canada, Ontario
Centre for Addiction and Mental Health Recruiting
Toronto, Ontario, Canada, M5T 1R8
Principal Investigator: Tony P George, M.D.         
Sponsors and Collaborators
Centre for Addiction and Mental Health
Canadian Institutes of Health Research (CIHR)
Investigators
Principal Investigator: Tony P George, M.D. Centre for Addiction and Mental Health, Schizophrenia Program, Toronto, ON, Canada
  More Information

Additional Information:
No publications provided

Responsible Party: Tony George, Professor, MD, Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier: NCT01523730     History of Changes
Other Study ID Numbers: rTMSlab#126/2011
Study First Received: January 25, 2012
Last Updated: March 17, 2014
Health Authority: Canada: Canadian Institutes of Health Research

Keywords provided by Centre for Addiction and Mental Health:
Schizophrenia
Nicotine
Transcranial Magnetic Stimulation
Cognition
EEG

Additional relevant MeSH terms:
Tobacco Use Disorder
Schizophrenia
Behavior, Addictive
Smoking
Substance-Related Disorders
Mental Disorders
Schizophrenia and Disorders with Psychotic Features
Compulsive Behavior
Impulsive Behavior
Habits

ClinicalTrials.gov processed this record on April 23, 2014