Working Memory Training Combined With Transcranial Magnetic Stimulation in Smokers
1 other identifier
interventional
50
1 country
2
Brief Summary
Smoking remains the leading cause of preventable death in the United States, and current first-line treatments leave the majority of tobacco dependent individuals unable to quit. The inability to quit despite motivation to do so, is thought to result in part, from self-control failure. Working memory (WM) deficits contribute to imbalanced self-control and allow automatic impulses to drive behavior. Thus, WM plays a critical role in addictive behavior, and is particularly relevant to smoking. Indeed, a strong link between WM and smoking has been established in the literature; most notably, degree of WM impairment and deficits in activation in associated brain regions predict time to relapse, and WM moderates the relationship between craving and relapse. Given these insights, researchers have been examining interventions that may target WM including WM training (WMT) and repetitive Transcranial Magnetic Stimulation (rTMS). WMT involves taxing this executive function repeatedly over time and has shown positive preliminary results in improving measures of self-control and reducing consumption of addictive substances. Similarly, rTMS, a non-invasive brain stimulation procedure that stimulates neuronal tissues and increases cortical excitability, has been shown to increase WM capacity and reduce craving and consumption of several addictive substances including nicotine. While these interventions have demonstrated initial promise in affecting addictive behaviors, the magnitude and durability of their effects may be limited. Recently, researchers have posited - but not yet empirically tested - that WMT administered in combination with rTMS may result in an additive or supra-additive effect in treating addictive processes. This is highly significant; the clinical utility of rTMS over current first line treatments may be limited if factors with potential to enhance its effectiveness are not examined. Given these recent advances in the literature, the primary objective of the proposed study is to evaluate the individual and combined effects of Working Memory (WM) training and repetitive Transcranial Magnetic Stimulation (rTMS) on WM performance and smoking behaviors as well as critical mediators of these effects. These aims will be examined in a sample of tobacco dependent adults (N=130) utilizing a 2x2 factorial experimental 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Mar 2018
Typical duration for phase_2
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 25, 2017
CompletedFirst Posted
Study publicly available on registry
November 8, 2017
CompletedStudy Start
First participant enrolled
March 5, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 31, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
January 31, 2021
CompletedResults Posted
Study results publicly available
May 2, 2022
CompletedMay 2, 2022
April 1, 2022
2.9 years
October 25, 2017
January 24, 2022
April 29, 2022
Conditions
Outcome Measures
Primary Outcomes (5)
Time to Lapse on a Smoking Lapse Analogue Task
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.
an average of 30 days after baseline
Working Memory Performance 1
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).
Change from baseline score to score at 30 days
Working Memory Performance 2
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
Working Memory Performance 3
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
Cigarette Consumption
Self reported number of cigarettes smoked daily
throughout 60 day study participation, cigarettes per day assessed at outcome reported
Secondary Outcomes (2)
Delay Discounting
Change from baseline score to score at 30 days
Cigarette Demand
Change from baseline score to score at 30 days
Study Arms (4)
WMT + rTMS
EXPERIMENTALWMT + rTMS is the Working Memory Training + repetitive Transcranial Magnetic Stimulation arm. Both conditions are active.
Sham WMT + rTMS
ACTIVE COMPARATORSham WMT + rTMS is the sham Working Memory Training + repetitive Transcranial Magnetic Stimulation arm. This condition isolates the effects of rTMS. WMT is inactive.
WMT + sham rTMS
ACTIVE COMPARATORWMT + sham rTMS is the Working Memory Training + sham repetitive Transcranial Magnetic Stimulation arm. This condition isolates the effects of WMT. rTMS is inactive.
Sham WMT + sham rTMS
SHAM COMPARATORsham WMT + sham rTMS is the sham Working Memory Training + sham repetitive Transcranial Magnetic Stimulation arm. Both are inactive in this arm.
Interventions
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.
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.
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.
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.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Kent State Universitylead
- Brown Universitycollaborator
- Butler Hospitalcollaborator
Study Sites (2)
Brown University
Providence, Rhode Island, 02906, United States
Butler Hospital
Providence, Rhode Island, 02906, United States
Related Publications (1)
Lechner WV, Philip NS, Kahler CW, Houben K, Tirrell E, Carpenter LL. Combined Working Memory Training and Transcranial Magnetic Stimulation Demonstrates Low Feasibility and Potentially Worse Outcomes on Delay to Smoking and Cognitive Tasks: A Randomized 2 x 2 Factorial Design Pilot and Feasibility Study. Nicotine Tob Res. 2022 Nov 12;24(12):1871-1880. doi: 10.1093/ntr/ntac183.
PMID: 35907262DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- William Lechner
- Organization
- Kent State University
Study Officials
- PRINCIPAL INVESTIGATOR
William V Lechner, Ph.D.
Kent State University
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, CARE PROVIDER
- Masking Details
- The participant will be prevented from having knowledge of the interventions assigned.
- Purpose
- TREATMENT
- Intervention Model
- FACTORIAL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Assistant Professor
Study Record Dates
First Submitted
October 25, 2017
First Posted
November 8, 2017
Study Start
March 5, 2018
Primary Completion
January 31, 2021
Study Completion
January 31, 2021
Last Updated
May 2, 2022
Results First Posted
May 2, 2022
Record last verified: 2022-04