- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03337113
Working Memory Training Combined With Transcranial Magnetic Stimulation in Smokers
Working Memory Training Combined With Transcranial Magnetic Stimulation in Smokers: 2x2 Factorial Study
Study Overview
Status
Conditions
Detailed Description
SPECIFIC AIMS Smoking remains the leading cause of preventable death in the U.S. Current first line treatments leave approximately 70% of tobacco dependent individuals unsuccessful in their attempt to quit. Specifically, only 5-30% of those who initiate treatment, including intensive first-line interventions, are able to maintain abstinence for one or more years. The inability to quit despite motivation to do so is thought to result, in part, from self-control failure and can be understood within the framework of dual process models of addiction. Dual process models view vulnerability to tobacco dependence as the relative balance between automatic impulses and control processes orchestrated through the interplay of multiple executive function. Working memory (WM) is an executive function associated with updating information to solve immediate problems, and achieve current goals. WM is a key cognitive process underlying the regulatory control component of dual process models and is involved in the initiation, maintenance, and relapse stages of tobacco dependence. Most notably, deficits in WM performance and activation in associated brain regions predict time to relapse and strong WM has been shown to reduce the effect of craving on the ability to resist smoking. Given this relationship, individuals with tobacco dependence are likely to benefit from interventions that strengthen WM. Recently, several studies have demonstrated that increasing WM capacity through WM training (WMT) is associated with positive outcomes in several populations with substance use or impulse control disorders. Specifically, studies have demonstrated that WMT is associated with decreased: delay discounting in substance users, weight re-gain after a weight loss program, and alcohol use in heavy drinkers.
A second emerging innovation in the treatment of addictions is repetitive Transcranial Magnetic Stimulation (rTMS), a procedure which sends magnetic pulses through the scalp to stimulate neuronal tissue resulting in observed changes in neuronal plasticity and striatal dopamine. rTMS has now demonstrated positive effects in several substance use disorders including nicotine, alcohol, and stimulant dependence. This procedure has been shown to be effective in reducing smoking urges in abstinent as well as satiated smokers and to reduce cigarette consumption. While promising results for this treatment have been demonstrated, the size and durability of the therapeutic effect may be limited. Additionally, the mechanism by which rTMS exerts positive effects on smoking outcomes is unknown. Recently it has been posited that changes in WM performance resulting from rTMS may be the key pathway to its observed effects on smoking related outcomes, and furthermore that WMT administered in close temporal precedence to rTMS may result in an additive or supra-additive effect in treating addictive processes. However, these hypotheses have not been tested to date despite their importance for understanding and improving the clinical impact of these emerging therapeutic modalities for treating addictive behaviors. Interventions with the ability to effectively target self-control processes fill in a critical gap in currently available treatment options.
The primary objective of the proposed study is to evaluate the potential for improved effects and examine mediating pathways of WMT in combination with rTMS on a laboratory based smoking task and neuropsychological measures of WM performance. These aims will be examined in a sample of tobacco dependent adults (N=130) utilizing a 2x2 factorial design including four groups (WMT+rTMS, sham WMT+rTMS, WMT+sham TMS, and sham WMT+sham rTMS) capable of isolating independent and combined effects of WMT and rTMS. The study will include a baseline laboratory assessment, 10 WMT sessions over two weeks, followed by 10 days of WMT immediately preceding and following brain stimulation sessions (10 Hz rTMS, 2000 pulses per session, applied to left DLPFC). Neurocognitive and psychological mediators will be assessed between baseline and final laboratory assessment. Lastly, a follow-up assessment will occur one-month after the final laboratory visit. The proposed study will test the following Specific Aims:
Aim 1: To test the potential for improved effects of combining WMT with rTMS on smoking behaviors as compared to the independent effects of either condition alone. Hypothesis: Single active conditions (WMT+sham rTMS and sham WMT+rTMS) will result in significant increases in time to lapse on an analogue task as compared to the double sham condition (sham WMT+sham rTMS), and the WMT+rTMS condition will result in significant increases in time to lapse as compared to the single active conditions.
Aim 2: To test the potential for improved effects of combining WMT with rTMS on WM performance.
Hypothesis: WMT + rTMS will result in significant increases in WM performance as compared to all other conditions, including the additive increases in conditions outlined in Aim 1.
Aim 3: To test mediating pathways of the effects rTMS on smoking behaviors including changes in craving, mood, and WM performance. Hypothesis: The direct effect of rTMS on smoking outcomes will be mediated by gains in WM performance, and this effect will be largest in the WMT+rTMS condition.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
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Rhode Island
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Providence, Rhode Island, United States, 02906
- Butler Hospital
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Providence, Rhode Island, United States, 02906
- Brown University
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- meet safety guidelines for application of rTMS
- be 18-60 years of age
- have smoked cigarettes regularly for at least one year
- currently smoke at least 10 cigarettes per day
- have a carbon monoxide (CO) level >10 ppm
- currently use no other nicotine products regularly
Exclusion Criteria:
- meet criteria for current alcohol or substance dependence
- have a current affective disorder (depression, dysthymia, or mania) or psychotic symptoms
- are currently pregnant or lactating, or intend to become pregnant
- have a health condition for which rTMS is contraindicated
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: FACTORIAL
- Masking: DOUBLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: WMT + rTMS
WMT + rTMS is the Working Memory Training + repetitive Transcranial Magnetic Stimulation arm.
Both conditions are active.
|
The Working Memory Training condition: This condition will include 30 sessions across 4 weeks (10 remote sessions prior to initiation of the rTMS stimulation, and 20 lab sessions on rTMS stimulation days).
Participants will complete three distinct WM tasks in each session: a visuospatial WM task, a backward digit span task, and a letter span task.
In the training condition, the difficulty level of all three WM tasks will be automatically adjusted on a trial-by-trial basis.
An identical protocol and software have demonstrated efficacy in increasing WM capacity, and this improvement in WM predicts reduction in addictive behavior.
Other Names:
The rTMS Condition: rTMS will be delivered with a Magstim Rapid2 system using Magstim Air Film Coils.
rTMS pulses will be delivered at 10 Hz (100% resting motor threshold, RMT) in 40, 5 second trains, with 15 second inter-train interval, for a total of 2000 pulses per session.
Active or sham rTMS will be applied over the left DLPFC; corresponding with the standard "F3" location on scalp (F3=left frontal lobe, location #3 for electrode placement using international 10-20 system for scalp measurements).
Five consecutive daily sessions will occur on two consecutive weeks, for a total of 10 sessions.
RMT, defined as the amount of energy required to induce movement in the contralateral abducer pollicis brevis in at least 50% of stimulations, will be assessed on first day of application.
Other Names:
|
ACTIVE_COMPARATOR: Sham WMT + rTMS
Sham WMT + rTMS is the sham Working Memory Training + repetitive Transcranial Magnetic Stimulation arm.
This condition isolates the effects of rTMS.
WMT is inactive.
|
The rTMS Condition: rTMS will be delivered with a Magstim Rapid2 system using Magstim Air Film Coils.
rTMS pulses will be delivered at 10 Hz (100% resting motor threshold, RMT) in 40, 5 second trains, with 15 second inter-train interval, for a total of 2000 pulses per session.
Active or sham rTMS will be applied over the left DLPFC; corresponding with the standard "F3" location on scalp (F3=left frontal lobe, location #3 for electrode placement using international 10-20 system for scalp measurements).
Five consecutive daily sessions will occur on two consecutive weeks, for a total of 10 sessions.
RMT, defined as the amount of energy required to induce movement in the contralateral abducer pollicis brevis in at least 50% of stimulations, will be assessed on first day of application.
Other Names:
In the Sham WMT condition, the difficulty level of the WM tasks will not be adjusted; instead it will remain at the initial easy level throughout each task (i.e., three items in each sequence).
All other aspects of the condition are identical to the active WMT condition.
Other Names:
|
ACTIVE_COMPARATOR: WMT + sham rTMS
WMT + sham rTMS is the Working Memory Training + sham repetitive Transcranial Magnetic Stimulation arm.
This condition isolates the effects of WMT.
rTMS is inactive.
|
The Working Memory Training condition: This condition will include 30 sessions across 4 weeks (10 remote sessions prior to initiation of the rTMS stimulation, and 20 lab sessions on rTMS stimulation days).
Participants will complete three distinct WM tasks in each session: a visuospatial WM task, a backward digit span task, and a letter span task.
In the training condition, the difficulty level of all three WM tasks will be automatically adjusted on a trial-by-trial basis.
An identical protocol and software have demonstrated efficacy in increasing WM capacity, and this improvement in WM predicts reduction in addictive behavior.
Other Names:
Sham rTMS will be identical to active treatment, with the exception that mu-metal plates attached to the sham coil block the magnetic field while providing a sensation of stimulation.
Other Names:
|
SHAM_COMPARATOR: Sham WMT + sham rTMS
sham WMT + sham rTMS is the sham Working Memory Training + sham repetitive Transcranial Magnetic Stimulation arm.
Both are inactive in this arm.
|
In the Sham WMT condition, the difficulty level of the WM tasks will not be adjusted; instead it will remain at the initial easy level throughout each task (i.e., three items in each sequence).
All other aspects of the condition are identical to the active WMT condition.
Other Names:
Sham rTMS will be identical to active treatment, with the exception that mu-metal plates attached to the sham coil block the magnetic field while providing a sensation of stimulation.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to Lapse on a Smoking Lapse Analogue Task
Time Frame: an average of 30 days after baseline
|
The Delay to Smoking Analogue Task is a behavioral choice paradigm that is sensitive to smoking medication effects in which participants earn monetary rewards for delaying initiation of cigarette smoking in 5-minute increments over a 50-minute period, following 3-hours of observed smoking deprivation.
Range = 0 - 50 minutes.
Higher scores indicate better ability to delay smoking.
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an average of 30 days after baseline
|
Working Memory Performance 1
Time Frame: Change from baseline score to score at 30 days
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NIH Examiner N-back score.
The minimum value is 0 and maximum is 90, higher scores indicate a better outcome.
Calculated change scores are presented (outcome score at day 30 minus baseline score).
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Change from baseline score to score at 30 days
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Working Memory Performance 2
Time Frame: Change from baseline score to score at 30 days
|
NIH Examiner Dot Counting Task score.
The minimum total score is 0 and the maximum score is 27, higher scores indicate a better outcome.
Calculated change scores are presented (outcome score at day 30 minus baseline score).
|
Change from baseline score to score at 30 days
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Working Memory Performance 3
Time Frame: Change from baseline score to score at 30 days
|
Mean End Level Score on Maastricht University Working Memory Tasks.
For each scale (i.e.
visuospatial, back-digit, and letter-sequencing) the minimum total is 3 and the maximum is 15, higher scores indicate a better outcome.
|
Change from baseline score to score at 30 days
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Cigarette Consumption
Time Frame: throughout 60 day study participation, cigarettes per day assessed at outcome reported
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Self reported number of cigarettes smoked daily
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throughout 60 day study participation, cigarettes per day assessed at outcome reported
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Delay Discounting
Time Frame: Change from baseline score to score at 30 days
|
Discounting Rate on the Monetary Choice Questionnaire, assessed by k (log transformed). Individuals made hypothetical choices between smaller immediate rewards (e.g. $11 today) and larger delayed rewards (e.g. $30 in 7 days) at varying levels of hyperbolic-like discounting. Overall temporal discounting function (k) was assessed; larger values indicate steeper discounting which reflects a worse outcome. Total score range = 0 - 0.25. |
Change from baseline score to score at 30 days
|
Cigarette Demand
Time Frame: Change from baseline score to score at 30 days
|
Demand characteristics on the Cigarette Purchase Task.
Demand sensitivity indicates sensitivity to change in price, with higher values reflecting higher sensitivity to the monetary reinforcer rather than the substance, thus higher scores reflect a better outcome.
Score range = 0 - .100.
|
Change from baseline score to score at 30 days
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: William V Lechner, Ph.D., Kent State University
Publications and helpful links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1705-003
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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