Nicotine Use DisorderNCT05766254
Identify the Optimal TMS Target to Modulate Reward Activity
A study testing Active 10-Hz TMS to the DLPFC in people with Nicotine Use Disorder, run by Rutgers, The State University of New Jersey at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Nicotine Use Disorder
- What is being tested?
- Active 10-Hz TMS to the DLPFC
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Mar 2023to Sep 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Rutgers University - Newark
Newark, New Jersey, 07102
Travis E Baker, PhD, 973-353-5485, travis.e.baker@rutgers.edu
Nicole Lalta, 973-353-3509, nicole.lalta@rutgers.edu
About this study
Official title: Identify the Optimal TMS Target to Modulate Midcingulate Reward Activity in Smokers
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.
Read the 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.
- Conditions
- Nicotine Use Disorder
- Being tested
- Active 10-Hz TMS to the DLPFC, Sham TMS-DLPFC
- Keywords
- transcranial magnetic stimulation, reward processing, EEG, neuroimaging
- Medical subject headings
- Tobacco Use Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active 10-Hz TMS to the DLPFCDevice
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.
Sham TMS-DLPFCDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Active TMS | Experimental | 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. Receives: Device: Active 10-Hz TMS to the DLPFC |
| Sham TMS | Sham comparator | Identical parameters will be applied to the SHAM group with the exception that the TMS coil will be flipped 180º to mimic auditory stimulation. Receives: Device: Sham TMS-DLPFC |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 0 (day of testing)
Secondary outcomes (3)
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.
Measured: Day 0 (day of testing)
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.
Measured: Day 0 (day of testing)
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.
Measured: Day 0 (day of testing - before and after TMS)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2023
- Study start24 Mar 2023
- Primary completionSep 2026 (estimated)
- Study completionSep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nicotine Use DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rutgers, The State University of New Jersey
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Travis Baker, PhD, Rutgers, The State University of New Jersey
- Investigators
- Travis E Lalta, PhD, Principal investigator, Rutgers University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05766254
- Sponsor's protocol ID
- Pro2022000444
- Status last verified
- Nov 2025
- First submitted
- 21 Feb 2023
- Last updated
- 17 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No: Data may be uploaded to an open source framework. All data will be deidentified.
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identify the Optimal TMS Target to Modulate Midcingulate Reward Activity in Smokers
- ClinicalTrials.gov ID
- NCT05766254
- Acronym / sponsor ID
- Pro2022000444
- Conditions
- Nicotine Use Disorder
- Keywords
- transcranial magnetic stimulation, reward processing, EEG, neuroimaging
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Rutgers, The State University of New JerseyUniversity, hospital or other
- Study start
- 24 Mar 2023 (actual)
- Primary completion
- Sep 2026 (estimated)
- Study completion
- Sep 2026 (estimated)
- First posted
- 13 Mar 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active TMS | Experimental | Device: Active 10-Hz TMS to the DLPFCParticipants 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. |
| Sham TMS | Sham comparator | Device: Sham TMS-DLPFCIdentical parameters will be applied to the SHAM group with the exception that the TMS coil will be flipped 180º to mimic auditory stimulation. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Active 10-Hz TMS to the DLPFCThe 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. | Device | Active TMS |
| Sham TMS-DLPFCThe parameters in the active arms will be as above with the internal randomization of the device internally switching to sham in a blinded fashion. | Device | Sham TMS |
Primary outcome
Event-related Brain Potential: Reward Positivity
Time frame: Day 0 (day of testing)
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.
3 secondary outcomes
Approach Learning
Time frame: Day 0 (day of testing)
Avoidance Learning
Time frame: Day 0 (day of testing)
Nicotine Craving
Time frame: Day 0 (day of testing - before and after TMS)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2025.
- Individual participant dataSharing planned: No. Data may be uploaded to an open source framework. All data will be deidentified.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Travis E Lalta, PhD principal investigator
Rutgers University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active 10-Hz TMS to the DLPFC in people with Nicotine Use Disorder, run by Rutgers, The State University of New Jersey at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Travis E Baker, PhD (973-353-5485, travis.e.baker@rutgers.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event-related Brain Potential: Reward Positivity (time frame: Day 0 (day of testing)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Nov 2025; AzTrials last refreshed its copy on 31 Oct 2026.