RTMS Targets Neural Circuits for Smoking Cessation

April 13, 2026 updated by: Xingbao L, Medical University of South Carolina

RTMS Manipulates Imbalanced Drive-reward and Executive Control Circuitry for Smoking Cessation

Cigarette smoking is a significant public health concern. Transcranial magnetic stimulation (TMS) is a non-invasive form of brain stimulation that has already displayed remarkable potential for producing novel, non-pharmacological interventions for depression and cigarette smokers. In this study, investigators will use brain MRI to guide TMS therapy for smoking cessation.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Smoking cessation is difficult, despite the demonstrated efficacy of several pharmacotherapeutic agents and cognitive behavioral therapies. This may be due to imbalanced neuronal circuits, including elevated functional connectivity in the drive-reward circuit (medial orbital frontal cortex [mOFC] to nucleus accumbens [NAc]) and decreased functional connectivity in the executive control circuit (dorsolateral prefrontal cortex[ DLPFC] to NAc). Repetitive transcranial magnetic stimulation (rTMS) is a new class of therapeutics that has already displayed remarkable potential for producing novel, non-pharmacological interventions for neuropsychiatric disorders. Previous studies have reported that rTMS decreased cue craving, reduced cigarette consumption, and increased smoking quit rate in tobacco use disorders(TUDs). However, the treatment parameters and exact mechanism for rTMS increasing smoking quit rate need further refinement. The goal of this study is to develop a circuit-based precision rTMS therapy for smoking cessation further. In the 3-year UH3 phase, investigators will conduct a randomized, double-blinded, sham-controlled trial of rTMS in 64 treatment-seeking tobacco use disorders (TUDs) smokers. Participants will be randomized to one of two conditions:

1. Sham rTMS, or 2. Active 10 Hz personalized-fMRI and E-field-modeling guided rTMS over the left dorsolateral prefrontal cortex (DLPFC). All participants will receive 20 daily sessions of rTMS over 4 weeks. Functional MRI scans will be performed prior to the first TMS treatment, after TMS session 10, and after the last TMS treatment session. All participants will have a one-week follow-up and 4 monthly follow-up visits (after the last TMS session 1 week, 1 month, 2 months, 3 months, and 4 months) after the last TMS session.

Study Type

Interventional

Enrollment (Estimated)

64

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Xingbao Li, MD, MSCR, MS
  • Phone Number: 843-792-5729
  • Email: lixi@musc.edu

Study Contact Backup

Study Locations

  • United States
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Recruiting
        • Medical University of South Carolina
        • Contact:
          • Xingbao Li, MD, MSCR, MS
          • Phone Number: 843-792-5729
          • Email: lixi@musc.edu
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria

  • Be between the ages of 22 and 70 years old.
  • Smoke 10 or more cigarettes per day and have a carbon monoxide (CO) level > 10 ppm indicative of recent smoking.
  • Have not received substance abuse treatment within the previous 30 days.
  • Meet the criteria for tobacco use disorder as determined by DSM-5.
  • Be in stable mental and physical health.
  • If female, test non-pregnant and use adequate birth control.
  • Show no evidence of focal or diffuse brain lesions on MRI.
  • Be willing to provide informed consent.
  • Be able to comply with protocol requirements and likely to complete all study procedures.
  • Be motivated to quit smoking (based on responses of "very likely," or "somewhat likely" in the motivation questionnaire).

Exclusion Criteria

  • Current moderate to severe substance use of any psychoactive substances other than nicotine or caffeine, as defined by DSM-V criteria.
  • Contraindications to MRI (e.g., presence of metal in the skull, orbital or intracranial cavity, or having claustrophobia).
  • Contraindication to rTMS.
  • History of autoimmune, endocrine, viral, or vascular disorders affecting the brain.
  • History or MRI evidence of neurological disorder that would lead to local or diffuse brain lesions or significant physical impairment.
  • Unstable cardiac disease, uncontrolled hypertension, severe renal or liver insufficiency, or sleep apnea.
  • Lifetime history of major Axis I disorders such as: bipolar affective disorder (BPAD), schizophrenia, post-traumatic stress disorder (PTSD), dementia, suicidal ideation or major depression.
  • Self-report of >21 standard alcohol drinks per week in any week in the 30 days prior to screening.
  • Use of other forms of nicotine delivery, such as nicotine patches, electronic cigarettes, gum, nasal spray, inhalers, and nicotine lozenges.
  • Use of other tobacco products, including cigars, cigarillos, chew, snuff, and pouches/snus.
  • Previous treatment with TMS.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Active rTMS 10 Hz DLPFC
A stimulation frequency of 10 Hz, pulse train duration (on time) of 5 seconds, inter-train interval (off time) of 10 seconds (15 second cycle time), E-field-modeling to determine TMS intensity and coil orientation, total of 60 trains, session time of 15 minutes, and 3000-total pulses per day, will be delivered over the left DLPFC.
Device: Active rTMS 10 Hz DLPFC
10 Hz repetitive transcranial magnetic stimulation (rTMS) will be delivered over left dorsolateral prefrontal cortex (DLPFC).
Sham Comparator: Sham rTMS
Investigators will use electrode stimulation with 10 Hz over DLPFC, total 3000 pulses. The sham-TMS scalp discomfort was matched to that of active TMS. During real TMS there was no current flowing through the scalp electrodes.
Device: Sham rTMS
Two electrodes on the scalp will be connected to transcutaneous electrical nerve stimulation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
4 week continue quit rate
Time Frame: 20 weeks
Measured by self-report of smoking abstinence in the past 4 weeks and confirmed using urine cotinine measurement.
20 weeks
Task-functional connectivity from functional magnetic resonance imaging (fMRI)
Time Frame: 4 week
The strength of functional connectivity is used to present the brain activities. The fMRI scans will be measured before the first TMS, after 2 weeks TMS and after the last TMS treatment.
4 week
Cigarette per day
Time Frame: 20 weeks
Cigarette per day (CPD) is measured to index smoking reduction and cigarette consumption.
20 weeks
Adverse Event
Time Frame: 4 weeks
Participants will be asked about adverse events (AE) each visit during treatment. AEs will be measured each TMS treatment visit.
4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Craving for cigarettes
Time Frame: 4 weeks
Measured with a visual analog scale (VAS). The VAS has 1-7 score. The minimum is 1 which means the lowest craving for smoking. The maximum value is 7 which is the highest craving for cigarettes. Participants will be asked to complete the scale each treatment visit.
4 weeks
Prolonged abstinence rate from end of treatment (Week 4) to end of follow-up (Week 20).
Time Frame: 20 weeks
Measured by self-report of smoking abstinence and confirmed using urine cotinine measurement.
20 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical University of South Carolina

Collaborators

National Institute on Drug Abuse (NIDA)

Investigators

  • Principal Investigator: Xingbao Li, MD, MSCR, MS, Medical University of South Carolina

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 15, 2021

Primary Completion (Estimated)

February 28, 2027

Study Completion (Estimated)

April 4, 2027

Study Registration Dates

First Submitted

May 21, 2021

First Submitted That Met QC Criteria

May 21, 2021

First Posted (Actual)

May 26, 2021

Study Record Updates

Last Update Posted (Actual)

April 16, 2026

Last Update Submitted That Met QC Criteria

April 13, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00105723
  • UH3DA048507-03 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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

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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