Ignite Creation Date:
2024-05-05 @ 9:45 PM
Last Modification Date:
2024-10-26 @ 10:08 AM
Study NCT ID:
NCT00951782
Status:
COMPLETED
Last Update Posted:
2013-12-20
First Post:
2009-07-14
Brief Title:
Deep High-Frequency Repetitive Transcranial Magnetic Stimulation for Smoking Cessation
Sponsor:
BeerYaakov Mental Health Center
Organization:
BeerYaakov Mental Health Center
Study Overview
Official Title:
Deep High-Frequency Repetitive Transcranial Magnetic Stimulation for Smoking Cessation in Patients With Chronic Obstructive Pulmonary Disease COPD
Status:
COMPLETED
Status Verified Date:
2013-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
TMS
Brief Summary:
Deep transcranial magnetic stimulation TMS is currently being evaluated as a treatment option in major depression It has been shown to be a safe procedure Deep transcranial magnetic stimulation coils are designed to maximize the electrical field deep in the brain by the summation of separate fields projected into the skull from several points around its periphery The device is planned to minimize the accumulation of electrical charge on the surface of the brain Such accumulation can give rise to an electrostatic field that might reduce the magnitude of the induced electric field both at the surface and inside thus reducing the depth penetration of the induced electric field Deep transcranial magnetic stimulation could be more effective than repetitive transcranial magnetic stimulation due to its deeper penetration into brain tissues The deeper penetration should produce greater action on nerve fibers connecting the prefrontal cortex to the limbic system
The ability of high-frequency repetitive transcranial magnetic stimulation rTMS to alter dopaminergic neurotransmission in subcortical structures could explain recent reports which suggest that it has the potential to reduce smoking and nicotine craving Ecihhammer et al demonstrated a reduction in the number of cigarettes smoked and in the desire to smoke after a single rTMS treatment Eichhammer et al 2003 In addition Johan et al in a cross-over double-blind placebo-controlled study demonstrated a reduction in cigarette consumption and desire to smoke after a single repetitive transcranial magnetic stimulation treatment Johann et al 2003 Recently the investigators have finished a complete study on nicotine addiction using repetitive transcranial magnetic stimulation for 10 consecutive days They have found that 10 days of rTMS reduced significantly better from placebo the number of cigarettes smoked nicotine dependence and craving Amiaz et al 2007 in preparation Interestingly some of the effects were stronger in the sub-group of patients that were presented with smoking-related pictures immediately prior to stimulation onset Although these results are interesting and exciting they have two important caveats First only about 50-60 of the smokers responded to the repetitive transcranial magnetic stimulation treatment Second among those responded to the treatment only 10 had quit totally from smoking Therefore the potential therapeutic benefit of this treatment is limited The investigators hypothesis is that deep transcranial magnetic stimulation may be more efficient in smoking cessation due to its deeper penetration and therefore its capability to stimulate deeper fibers of the dopamine-reward-activating system
The ability of high-frequency repetitive transcranial magnetic stimulation rTMS to alter dopaminergic neurotransmission in subcortical structures could explain recent reports which suggest that it has the potential to reduce smoking and nicotine craving Ecihhammer et al demonstrated a reduction in the number of cigarettes smoked and in the desire to smoke after a single rTMS treatment Eichhammer et al 2003 In addition Johan et al in a cross-over double-blind placebo-controlled study demonstrated a reduction in cigarette consumption and desire to smoke after a single repetitive transcranial magnetic stimulation treatment Johann et al 2003 Recently the investigators have finished a complete study on nicotine addiction using repetitive transcranial magnetic stimulation for 10 consecutive days They have found that 10 days of rTMS reduced significantly better from placebo the number of cigarettes smoked nicotine dependence and craving Amiaz et al 2007 in preparation Interestingly some of the effects were stronger in the sub-group of patients that were presented with smoking-related pictures immediately prior to stimulation onset Although these results are interesting and exciting they have two important caveats First only about 50-60 of the smokers responded to the repetitive transcranial magnetic stimulation treatment Second among those responded to the treatment only 10 had quit totally from smoking Therefore the potential therapeutic benefit of this treatment is limited The investigators hypothesis is that deep transcranial magnetic stimulation may be more efficient in smoking cessation due to its deeper penetration and therefore its capability to stimulate deeper fibers of the dopamine-reward-activating system
Detailed Description:
Research Plan
I PARTICIPANTS Male and female cigarette smokers who suffer from COPD From the general population aged 21-70 who wishes to quit smoking and failed to respond to previous anti-smoking treatment They will be recruited by advertisements in the newspapers and specific websites The number of participants in each sub-group as described in the table below will be 15-17 The investigators will recruit 90-102 subjects over two years
II SCREENING PROCEDURE
Before stimulation procedures onset participants will undergo a clinical interview All subject candidates will give written informed consent to take part in the study Thereafter they will be tested for their baseline pretreatment level of nicotine addiction in a screening meeting This includes a report on the level of consumption number of cigarettes smoked per day and overall duration in years and a visual analog scale VAS see below for details In addition a urine sample for cotinine levels nicotine metabolite will be obtained in order to objectively measure levels of nicotine In addition several self-administered questionnaires will be given to the subjects in order to measure their baseline craving and nicotine dependence
1 Fagerstrom Test of Nicotine Dependence FTND Heatherton et al 1991 Appendix no1a
2 Tobacco Craving Questionnaire TCQ Heishman et al 2003 Appendix no1b
3 Full demographic questionnaire about medical condition and smoking habits Appendix no1c
III MEASURES
All subjects will undergo various measurements on several visits as described in table 1-3 for nicotine consumption craving and dependence during the rTMS treatment visits
1 VAS Visual Analogue Scale on which the subject marks hisher subjective craving on a 10-cm-long scale in response to the following question How much do you crave a jointbong right now This desire to smoke rating has been shown to be sensitive to assess self-reported levels of craving in nicotine smoking Schuh and Stitzer 1995 King and Meyer 2000
2 Short TCQ Tobacco Craving Questionnaire the short version of the TCQ which has 12 questions that can be divided into four categories emotionality expectancy compulsivity and purposefulness
3 FTND Fagerstrom Test of Nicotine Dependence Measures the level of nicotine dependence Dijkstra and Tromp 2002
4 Self-report of the number of cigarettes smoked on the previous day
5 Urine sample
6 BR desire to smoke and effect on hunger
7 Spatial span memory test - in order to evaluate the effect of deep rTMS on spatial memory This test will be conducted in the screening interview and after 10 days of rTMS treatment
IV PRESENTATION OF PHOTOGRAPHS
It has recently been demonstrated that in nicotine-deprived smokers reward and attention circuits are reactivated by mere exposure to smoking-related images in contrast with neutral images Due et al 2002 In our experiment prior to stimulation onset 14 neutral or nicotine-related colored photographs will be presented on a computer screen to the participants while there are seated The nicotine-related photographs will be composed from smoking-related scenes such as lighting up a cigarette smoking puffs etc Neutral photos will consist of matched pictures without any nicotine related content eg inanimate objects hands faces etc As the investigators have previously shown with the figure-8 coil experiment there was a stronger effect of the rTMS treatment in subjects exposed to the nicotine photographs The investigators propose that presentation of the nicotine photographs causes the nicotine-related memories to become activated and therefore labile for interference as previously has been shown Dudai 2004
V EXPERIMENTAL PROCEDURES
After screening of the participants while taking into account the inclusion and exclusion criteria described above they will be divided into experimental groups having similar levels of nicotine addiction and demographic background At selected time afterwards participants will be introduced to the TMS treatment protocol They will be asked to refrain from smoking nicotine for two hours prior to attending the daily treatment session Prior to stimulation onset the participants will be presented with nicotine photographs Immediately after the offset of the photographs presentation while memory is reactivated the participants will be applied with real or sham rTMS stimulation The stimulation site will be the PFC using the H-ADD coil
Time Table
There will be daily treatments for two weeks accompanied with assessment of the level of nicotine addiction on selected days using the above-mentioned tools Thereafter subjects will continue to have maintenance rTMSsham stimulation treatment 3 times a week for one week two times a week in the forth and fifth week once a week in the sixth and seventh week see also table 2 After maintenance participants will continue with follow up visits that will occur once a month for six months see table 3 This protocol will allow evaluation of the short and long-term effects of the rTMS treatment with the possible fluctuations over time
TMS procedure
The investigators will use a Magstim Super Rapid stimulator which produces a biphasic pulse and our special customized equipment and coils for deep brain stimulation Zangen 2005 The TMS coils which will be used in this study will be specific versions of the H-coil depending on the region of stimulation The H-coil versions used in this study the H-ADD coil have been tested in healthy volunteers and found to be safe and to induce some short-lasting 1 hour cognitive alterations Levkovitz et al 2007 accepted The theoretical considerations and design principles of the H-coils are explained in a previous study Roth 2002 In short the H-ADD coil is designed to generate summation of the electric field in a specific brain region by locating coil elements at different locations around this region all of which have a common current component which induce electric field in the desired direction In addition since a radial component has a dramatic effect on electric field magnitude and on the rate of decay of the electric field with distance the overall length of coil elements which are nontangential to the skull should be minimized and these elements as well as coil elements having current component in the opposite direction should be located as distant as possible from the brain region to be activated
The H-ADD coil is placed on the scalp over the left motor cortex The center of the coil is placed on the scalp with the handle pointing backward and laterally at a 45 angle away from the midline Thus the current induced in the neural tissue is directed approximately perpendicular to the line of the central sulcus and therefore optimal for activating the corticospinal pathways transsynaptically Kaneko et al 1996 With a slightly suprathreshold stimulus intensity the stimulating H-ADD coil is moved over the left hemisphere to determine the optimal position for eliciting MEPs of maximal amplitudes the hot spot The optimal position of the coil is then marked relative to the hot spot to ensure coil placement throughout the experiment Resting motor threshold is determined to the nearest 1 of the maximum stimulator output and is defined as the minimal stimulus intensity required to produce MEPs of 50 µV in 5 of 10 consecutive trials at least 5 sec apart The H-ADD coil is held in a stable coil holder which can be adjusted at different points relative to the hot spot on the scalp
Stimulation Protocols
The investigators will use either sham or real H-ADD coils which both produce similar noise and share a similar shape as the investigators have been using in our study on healthy volunteers Stimulation intensity will be 120 relative to the motor threshold in the hot spot PFC location will be determined as follows 6 cm anterior to the motor hot spot and symmetric
High frequency stimulation will by applied in order to achieve activation of the stimulated brain area and possibly induce LTP like plasticity The stimulation protocol will be 33 trains of 10 Hz for 3 seconds ITI of 20 seconds The total treatment duration will be 759 seconds with 990 pulses For that purpose the investigators have designed a special cooling system for our coils and used them successfully in our healthy volunteers study Levkovitz et al 2007 accepted
I PARTICIPANTS Male and female cigarette smokers who suffer from COPD From the general population aged 21-70 who wishes to quit smoking and failed to respond to previous anti-smoking treatment They will be recruited by advertisements in the newspapers and specific websites The number of participants in each sub-group as described in the table below will be 15-17 The investigators will recruit 90-102 subjects over two years
II SCREENING PROCEDURE
Before stimulation procedures onset participants will undergo a clinical interview All subject candidates will give written informed consent to take part in the study Thereafter they will be tested for their baseline pretreatment level of nicotine addiction in a screening meeting This includes a report on the level of consumption number of cigarettes smoked per day and overall duration in years and a visual analog scale VAS see below for details In addition a urine sample for cotinine levels nicotine metabolite will be obtained in order to objectively measure levels of nicotine In addition several self-administered questionnaires will be given to the subjects in order to measure their baseline craving and nicotine dependence
1 Fagerstrom Test of Nicotine Dependence FTND Heatherton et al 1991 Appendix no1a
2 Tobacco Craving Questionnaire TCQ Heishman et al 2003 Appendix no1b
3 Full demographic questionnaire about medical condition and smoking habits Appendix no1c
III MEASURES
All subjects will undergo various measurements on several visits as described in table 1-3 for nicotine consumption craving and dependence during the rTMS treatment visits
1 VAS Visual Analogue Scale on which the subject marks hisher subjective craving on a 10-cm-long scale in response to the following question How much do you crave a jointbong right now This desire to smoke rating has been shown to be sensitive to assess self-reported levels of craving in nicotine smoking Schuh and Stitzer 1995 King and Meyer 2000
2 Short TCQ Tobacco Craving Questionnaire the short version of the TCQ which has 12 questions that can be divided into four categories emotionality expectancy compulsivity and purposefulness
3 FTND Fagerstrom Test of Nicotine Dependence Measures the level of nicotine dependence Dijkstra and Tromp 2002
4 Self-report of the number of cigarettes smoked on the previous day
5 Urine sample
6 BR desire to smoke and effect on hunger
7 Spatial span memory test - in order to evaluate the effect of deep rTMS on spatial memory This test will be conducted in the screening interview and after 10 days of rTMS treatment
IV PRESENTATION OF PHOTOGRAPHS
It has recently been demonstrated that in nicotine-deprived smokers reward and attention circuits are reactivated by mere exposure to smoking-related images in contrast with neutral images Due et al 2002 In our experiment prior to stimulation onset 14 neutral or nicotine-related colored photographs will be presented on a computer screen to the participants while there are seated The nicotine-related photographs will be composed from smoking-related scenes such as lighting up a cigarette smoking puffs etc Neutral photos will consist of matched pictures without any nicotine related content eg inanimate objects hands faces etc As the investigators have previously shown with the figure-8 coil experiment there was a stronger effect of the rTMS treatment in subjects exposed to the nicotine photographs The investigators propose that presentation of the nicotine photographs causes the nicotine-related memories to become activated and therefore labile for interference as previously has been shown Dudai 2004
V EXPERIMENTAL PROCEDURES
After screening of the participants while taking into account the inclusion and exclusion criteria described above they will be divided into experimental groups having similar levels of nicotine addiction and demographic background At selected time afterwards participants will be introduced to the TMS treatment protocol They will be asked to refrain from smoking nicotine for two hours prior to attending the daily treatment session Prior to stimulation onset the participants will be presented with nicotine photographs Immediately after the offset of the photographs presentation while memory is reactivated the participants will be applied with real or sham rTMS stimulation The stimulation site will be the PFC using the H-ADD coil
Time Table
There will be daily treatments for two weeks accompanied with assessment of the level of nicotine addiction on selected days using the above-mentioned tools Thereafter subjects will continue to have maintenance rTMSsham stimulation treatment 3 times a week for one week two times a week in the forth and fifth week once a week in the sixth and seventh week see also table 2 After maintenance participants will continue with follow up visits that will occur once a month for six months see table 3 This protocol will allow evaluation of the short and long-term effects of the rTMS treatment with the possible fluctuations over time
TMS procedure
The investigators will use a Magstim Super Rapid stimulator which produces a biphasic pulse and our special customized equipment and coils for deep brain stimulation Zangen 2005 The TMS coils which will be used in this study will be specific versions of the H-coil depending on the region of stimulation The H-coil versions used in this study the H-ADD coil have been tested in healthy volunteers and found to be safe and to induce some short-lasting 1 hour cognitive alterations Levkovitz et al 2007 accepted The theoretical considerations and design principles of the H-coils are explained in a previous study Roth 2002 In short the H-ADD coil is designed to generate summation of the electric field in a specific brain region by locating coil elements at different locations around this region all of which have a common current component which induce electric field in the desired direction In addition since a radial component has a dramatic effect on electric field magnitude and on the rate of decay of the electric field with distance the overall length of coil elements which are nontangential to the skull should be minimized and these elements as well as coil elements having current component in the opposite direction should be located as distant as possible from the brain region to be activated
The H-ADD coil is placed on the scalp over the left motor cortex The center of the coil is placed on the scalp with the handle pointing backward and laterally at a 45 angle away from the midline Thus the current induced in the neural tissue is directed approximately perpendicular to the line of the central sulcus and therefore optimal for activating the corticospinal pathways transsynaptically Kaneko et al 1996 With a slightly suprathreshold stimulus intensity the stimulating H-ADD coil is moved over the left hemisphere to determine the optimal position for eliciting MEPs of maximal amplitudes the hot spot The optimal position of the coil is then marked relative to the hot spot to ensure coil placement throughout the experiment Resting motor threshold is determined to the nearest 1 of the maximum stimulator output and is defined as the minimal stimulus intensity required to produce MEPs of 50 µV in 5 of 10 consecutive trials at least 5 sec apart The H-ADD coil is held in a stable coil holder which can be adjusted at different points relative to the hot spot on the scalp
Stimulation Protocols
The investigators will use either sham or real H-ADD coils which both produce similar noise and share a similar shape as the investigators have been using in our study on healthy volunteers Stimulation intensity will be 120 relative to the motor threshold in the hot spot PFC location will be determined as follows 6 cm anterior to the motor hot spot and symmetric
High frequency stimulation will by applied in order to achieve activation of the stimulated brain area and possibly induce LTP like plasticity The stimulation protocol will be 33 trains of 10 Hz for 3 seconds ITI of 20 seconds The total treatment duration will be 759 seconds with 990 pulses For that purpose the investigators have designed a special cooling system for our coils and used them successfully in our healthy volunteers study Levkovitz et al 2007 accepted
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None