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Identify the Optimal TMS Target to Modulate Reward Activity

Primary Purpose

Nicotine Use Disorder

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Active 10-Hz TMS to the DLPFC
Sham TMS-DLPFC
Sponsored by
Rutgers, The State University of New Jersey
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Nicotine Use Disorder focused on measuring transcranial magnetic stimulation, reward processing, EEG, neuroimaging

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Nicotine dependent individuals (according to the Alcohol, Smoking and Substance Involvement Screening Test nicotine dependence score). Be between the ages of 18 and 55 years old. Not received substance abuse treatment within the previous 30 days. Be in stable mental and physical health. If female, test non-pregnant. No evidence of focal or diffuse brain lesion on MRI. Be willing to provide informed consent. Be able to comply with protocol requirements and likely to complete all study procedures. Exclusion Criteria: Contraindication to MRI (e.g., presence of metal in the skull, orbits or intracranial cavity, claustrophobia). Contraindication to rTMS (history of neurological disorder or seizure, increased intracranial pressure, brain surgery, or head trauma with loss of consciousness for > 15 minutes, implanted electronic device, metal in the head, or pregnancy). History of autoimmune, endocrine, viral, or vascular disorder affecting the brain. History or MRI evidence of neurological disorder that would lead to local or diffuse brain lesions or significant physical impairment. Life time history of mental disorders such as: Bipolar Affective disorder (BPAD), Schizophrenia, Post-traumatic Stress disorder (PTSD) or Dementia or Major Depression. uninterruptable central nervous system medication

Sites / Locations

  • Rutgers University - NewarkRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Active TMS

Sham TMS

Arm Description

Participants in the active condition will receive repetitive TMS (rTMS), delivered at 110% of participants' resting motor threshold at 10 Hz continuously over the predefined prefrontal target for a total of 1000 pulses. Within each of the two TMS sessions, two targets will be stimulated.

Identical parameters will be applied to the SHAM group with the exception that the TMS coil will be flipped 180º to mimic auditory stimulation.

Outcomes

Primary Outcome Measures

Event-related Brain Potential: Reward Positivity
The reward positivity is an event-related brain potential (ERP) sensitive to reward feedback. The reward positivity will be measured during the T-maze task, where participants will receive feedback (Reward, No-reward) following choices. ERPs will be created for each electrode and participant by averaging the single-trial EEG according to feedback type (Reward, No-reward). The reward positivity will be evaluated by subtracting the Reward feedback ERPs from the corresponding No-reward feedback ERPs. The size of the reward positivity will then be determined by identifying the maximum absolute amplitude of the difference wave within a 200-to 400-msec window after feedback onset and evaluated along electrodes Fz, FCz, and Cz. The reward positivity will be measured for each proposed DLPFC target across active and sham groups of dependent smokers. The reward positivity will be used to measure the efficacy of the DLPFC target to modulate reward activity.

Secondary Outcome Measures

Approach Learning
Approach learning will be measured using a Probabilistic Selection task (PST), in which subjects are shown pairs of arbitrary stimuli and must learn by trial-and-error to select one of each pair. During an initial learning phase participants are exposed to three pairs of stimuli, each of the three pairs is rewarded on 80%, 70%, and 60% of the trials. Subjects learn by feedback that some stimuli are associated with more positive feedback (Approach) and that some stimuli are associated with more negative feedback (Avoidance). To determine whether subjects learn more from positive (approach) or negative (avoidance) feedback, during a subsequent testing phase they are required to choose between novel stimulus pairs. Approach learning (accuracy and reaction time) for each proposed DLPFC target across active and sham groups will be measured during the testing phase. Avoidance learning performance will be used to measure the efficacy of the DLPFC target to modulate decision making.
Avoidance Learning
Avoidance learning will be measured using a Probabilistic Selection task (PST), in which subjects are shown pairs of arbitrary stimuli and must learn by trial-and-error to select one of each pair. During an initial learning phase participants are exposed to three pairs of stimuli, each of the three pairs is rewarded on 80%, 70%, and 60% of the trials. Subjects learn by feedback that some stimuli are associated with more positive feedback (Approach) and that some stimuli are associated with more negative feedback (Avoidance). To determine whether subjects learn more from positive (approach) or negative (avoidance) feedback, during a subsequent testing phase they are required to choose between novel stimulus pairs. Avoidance learning (accuracy and reaction time) for each proposed DLPFC target across active and sham groups will be measured during the testing phase. Avoidance learning performance will be used to measure the efficacy of the DLPFC target to modulate decision making.
Nicotine Craving
The level of craving will be assessed in dependent smokers using the short version of the Tobacco Craving Questionnaire (TCQ), a 12-item scale that assesses state levels of craving. TCQ will be measured at the start of each session, and following each Block of TMS (once for each DLPFC target). We will compared the TCQ score from pre-TMS (start of session) to post-TMS.

Full Information

First Posted
February 21, 2023
Last Updated
April 12, 2023
Sponsor
Rutgers, The State University of New Jersey
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1. Study Identification

Unique Protocol Identification Number
NCT05766254
Brief Title
Identify the Optimal TMS Target to Modulate Reward Activity
Official Title
Identify the Optimal TMS Target to Modulate Midcingulate Reward Activity in Smokers
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 24, 2023 (Actual)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
September 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Rutgers, The State University of New Jersey

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Our primary goal will be to identify the optimal prefrontal-cingulate target by systematically measuring the efficacy of various image-based targeting techniques to increase the reward positivity using the 10-Hz TMS protocol in dependent smokers. Our secondary objective will be to measure the targets' effectiveness to increase decision-making capacity using the probabilistic selection task (PST). Our third objective will be to specifically assess whether the TMS targets has a differential impact on state levels of craving relative to baseline (Tobacco Craving Questionnaire [TCQ]. We plan to accomplish these three objectives using a randomized, controlled experiment involving 3 sessions.
Detailed Description
The design is primarily a randomized control-trial design (3 sessions), comparing the effects 10-Hz rTMS applied to four prefrontal TMS targets based on fMRI, cortical thickness (CT), diffusion-weighted imaging (DWI) and resting state functional connectivity (RSFC) on reward processing across two groups of smokers - Active TMS group and Sham TMS group. For Session A, participants will be scanned using a 3 Tesla MRI system and will receive a structural (T1), fMRI, DWI, and resting-state FC scan. Following Session A, all participants will be asked to complete two Ri-TMS sessions within two weeks and will be instructed to abstain from smoking for 4 hours before the start of each scheduled session. Session B and C: Distinct prefrontal target regions will be identified for each subject based on CT, fMRI, DWI, and RSFC data. At the start of Session B, a target will be randomly assigned to each subject using a random permuted block method. For Sessions B and C, participants will be asked to provide their consent, CO levels, and complete the craving questionnaire (TCQ). At the start of Session B, participants will be fitted with an EEG cap and engage in a virtual T-maze feedback task. The task will be divided into two blocks (200 trials per block: 10 minutes per block). At the start of Block 1, the robotic arm will position the TMS coil <1 cm over Target 1. Next, 50 rTMS pulses will be delivered at 110% of participants' rMT at 10- Hz continuously over Target 1 immediately before every 10 trials of the T-maze (5 seconds of TMS, 30 seconds of task). A total of 1000 pulses will be delivered to Target 1 and 200 T-maze trials completed (duration 10-15 minutes). Immediately after, subjects will be asked to complete a probabilistic selection task (PST) to measure post-stimulation effects on decision-making performance (duration, 15 minutes). Following the completion of the PST, subjects will be given a 5 minute rest-break and participants will be asked to fill out the TCQ. At the start of Block 2, the robotic arm will position the TMS coil <1 cm over Target 2, and 50 rTMS pulses will be delivered immediately before every 10 trials of the T-maze task. A total of 1000 pulses will be delivered to Target 2 and 200 T-maze trials completed (duration 10 minutes). Following Target 2 stimulation, subjects will be asked to complete the PST (duration, 15 minutes) and asked to fill out the TCQ. At the end of the Session B, participants will be scheduled to return to the laboratory to complete Session C on a separate day. An identical protocol will be applied to Session C with the exception that TMS pulses will be deliver to Target 3 and Target 4.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nicotine Use Disorder
Keywords
transcranial magnetic stimulation, reward processing, EEG, neuroimaging

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Masking Description
Single (Participant) Participants will be blinded as to TMS condition (active or sham)
Allocation
Randomized
Enrollment
36 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Active TMS
Arm Type
Experimental
Arm Description
Participants in the active condition will receive repetitive TMS (rTMS), delivered at 110% of participants' resting motor threshold at 10 Hz continuously over the predefined prefrontal target for a total of 1000 pulses. Within each of the two TMS sessions, two targets will be stimulated.
Arm Title
Sham TMS
Arm Type
Sham Comparator
Arm Description
Identical parameters will be applied to the SHAM group with the exception that the TMS coil will be flipped 180º to mimic auditory stimulation.
Intervention Type
Device
Intervention Name(s)
Active 10-Hz TMS to the DLPFC
Intervention Description
The active group will receive 10hz TMS stimulation. Participants in the active stimulation group will receive10-Hz TMS to left DLPFC. The LDLPFC will be based on 4 targeting neuroimaging methods (cortical thickness, fMRI, diffusion imaging, functional connectivity). TMS will be delivered using a robotic neuronavigation system (Smartmove, ANT). Stimulation intensity will be standardized at 110% of RMT and adjusted to the skull to cortical surface based on e-field calculations (simnibs). Stimulation will be delivered to the L-DLPFC using a active/placebo figure-8 coil and a magventure TMS device.
Intervention Type
Device
Intervention Name(s)
Sham TMS-DLPFC
Intervention Description
The parameters in the active arms will be as above with the internal randomization of the device internally switching to sham in a blinded fashion.
Primary Outcome Measure Information:
Title
Event-related Brain Potential: Reward Positivity
Description
The reward positivity is an event-related brain potential (ERP) sensitive to reward feedback. The reward positivity will be measured during the T-maze task, where participants will receive feedback (Reward, No-reward) following choices. ERPs will be created for each electrode and participant by averaging the single-trial EEG according to feedback type (Reward, No-reward). The reward positivity will be evaluated by subtracting the Reward feedback ERPs from the corresponding No-reward feedback ERPs. The size of the reward positivity will then be determined by identifying the maximum absolute amplitude of the difference wave within a 200-to 400-msec window after feedback onset and evaluated along electrodes Fz, FCz, and Cz. The reward positivity will be measured for each proposed DLPFC target across active and sham groups of dependent smokers. The reward positivity will be used to measure the efficacy of the DLPFC target to modulate reward activity.
Time Frame
Day 0 (day of testing)
Secondary Outcome Measure Information:
Title
Approach Learning
Description
Approach learning will be measured using a Probabilistic Selection task (PST), in which subjects are shown pairs of arbitrary stimuli and must learn by trial-and-error to select one of each pair. During an initial learning phase participants are exposed to three pairs of stimuli, each of the three pairs is rewarded on 80%, 70%, and 60% of the trials. Subjects learn by feedback that some stimuli are associated with more positive feedback (Approach) and that some stimuli are associated with more negative feedback (Avoidance). To determine whether subjects learn more from positive (approach) or negative (avoidance) feedback, during a subsequent testing phase they are required to choose between novel stimulus pairs. Approach learning (accuracy and reaction time) for each proposed DLPFC target across active and sham groups will be measured during the testing phase. Avoidance learning performance will be used to measure the efficacy of the DLPFC target to modulate decision making.
Time Frame
Day 0 (day of testing)
Title
Avoidance Learning
Description
Avoidance learning will be measured using a Probabilistic Selection task (PST), in which subjects are shown pairs of arbitrary stimuli and must learn by trial-and-error to select one of each pair. During an initial learning phase participants are exposed to three pairs of stimuli, each of the three pairs is rewarded on 80%, 70%, and 60% of the trials. Subjects learn by feedback that some stimuli are associated with more positive feedback (Approach) and that some stimuli are associated with more negative feedback (Avoidance). To determine whether subjects learn more from positive (approach) or negative (avoidance) feedback, during a subsequent testing phase they are required to choose between novel stimulus pairs. Avoidance learning (accuracy and reaction time) for each proposed DLPFC target across active and sham groups will be measured during the testing phase. Avoidance learning performance will be used to measure the efficacy of the DLPFC target to modulate decision making.
Time Frame
Day 0 (day of testing)
Title
Nicotine Craving
Description
The level of craving will be assessed in dependent smokers using the short version of the Tobacco Craving Questionnaire (TCQ), a 12-item scale that assesses state levels of craving. TCQ will be measured at the start of each session, and following each Block of TMS (once for each DLPFC target). We will compared the TCQ score from pre-TMS (start of session) to post-TMS.
Time Frame
Day 0 (day of testing - before and after TMS)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Nicotine dependent individuals (according to the Alcohol, Smoking and Substance Involvement Screening Test nicotine dependence score). Be between the ages of 18 and 55 years old. Not received substance abuse treatment within the previous 30 days. Be in stable mental and physical health. If female, test non-pregnant. No evidence of focal or diffuse brain lesion on MRI. Be willing to provide informed consent. Be able to comply with protocol requirements and likely to complete all study procedures. Exclusion Criteria: Contraindication to MRI (e.g., presence of metal in the skull, orbits or intracranial cavity, claustrophobia). Contraindication to rTMS (history of neurological disorder or seizure, increased intracranial pressure, brain surgery, or head trauma with loss of consciousness for > 15 minutes, implanted electronic device, metal in the head, or pregnancy). History of autoimmune, endocrine, viral, or vascular disorder affecting the brain. History or MRI evidence of neurological disorder that would lead to local or diffuse brain lesions or significant physical impairment. Life time history of mental disorders such as: Bipolar Affective disorder (BPAD), Schizophrenia, Post-traumatic Stress disorder (PTSD) or Dementia or Major Depression. uninterruptable central nervous system medication
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Travis E Baker, PhD
Phone
973-353-5485
Email
travis.e.baker@rutgers.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Nicole Lalta
Phone
973-353-3509
Email
nicole.lalta@rutgers.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Travis E Lalta, PhD
Organizational Affiliation
Rutgers University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rutgers University - Newark
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07102
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Travis E Baker, PhD
Phone
973-353-5485
Email
travis.e.baker@rutgers.edu
First Name & Middle Initial & Last Name & Degree
Nicole Lalta
Phone
973-353-3509
Email
nicole.lalta@rutgers.edu

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Data may be uploaded to an open source framework. All data will be deidentified.

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Identify the Optimal TMS Target to Modulate Reward Activity

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