RTMS Targets Neural Circuits for Smoking Cessation

NCT04903028 | Recruiting DMC FDA Device

• 2 other identifiers: Pro00105723UH3DA048507-03
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Tobacco Use; Cigarette Smoking

Keywords

Tobacco use disorder, rTMS, smoking cessation

Outcome Measures

Primary Outcomes (4)

• 4 week continue quit rate

  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)

  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

  Cigarette per day (CPD) is measured to index smoking reduction and cigarette consumption.

  20 weeks

• Adverse Event

  Participants will be asked about adverse events (AE) each visit during treatment. AEs will be measured each TMS treatment visit.

  4 weeks

Secondary Outcomes (2)

• Craving for cigarettes

  4 weeks

• Prolonged abstinence rate from end of treatment (Week 4) to end of follow-up (Week 20).

  20 weeks

Study Arms (2)

Sham rTMS

SHAM COMPARATOR

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

Active rTMS 10 Hz DLPFC

ACTIVE COMPARATOR

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

Interventions

Sham rTMS DEVICE

Two electrodes on the scalp will be connected to transcutaneous electrical nerve stimulation.

Sham rTMS

Active rTMS 10 Hz DLPFC DEVICE

10 Hz repetitive transcranial magnetic stimulation (rTMS) will be delivered over left dorsolateral prefrontal cortex (DLPFC).

Active rTMS 10 Hz DLPFC

Eligibility Criteria

• Age: 22 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Medical University of South Carolina: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (2)

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

RECRUITING

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

RECRUITING

Related Publications (8)

• Li X, Sahlem GL, Badran BW, McTeague LM, Hanlon CA, Hartwell KJ, Henderson S, George MS. Transcranial magnetic stimulation of the dorsal lateral prefrontal cortex inhibits medial orbitofrontal activity in smokers. Am J Addict. 2017 Dec;26(8):788-794. doi: 10.1111/ajad.12621. Epub 2017 Sep 12.

  PMID: 28898485 BACKGROUND

• Li X, Du L, Sahlem GL, Badran BW, Henderson S, George MS. Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex reduces resting-state insula activity and modulates functional connectivity of the orbitofrontal cortex in cigarette smokers. Drug Alcohol Depend. 2017 May 1;174:98-105. doi: 10.1016/j.drugalcdep.2017.02.002. Epub 2017 Feb 28.

  PMID: 28319755 BACKGROUND

• Dinur-Klein L, Dannon P, Hadar A, Rosenberg O, Roth Y, Kotler M, Zangen A. Smoking cessation induced by deep repetitive transcranial magnetic stimulation of the prefrontal and insular cortices: a prospective, randomized controlled trial. Biol Psychiatry. 2014 Nov 1;76(9):742-9. doi: 10.1016/j.biopsych.2014.05.020. Epub 2014 Jun 5.

  PMID: 25038985 BACKGROUND

• Li X, Toll BA, Carpenter MJ, Nietert PJ, Dancy M, George MS. Repetitive Transcranial Magnetic Stimulation for Tobacco Treatment in Cancer Patients: A Preliminary Report of a One-Week Treatment. J Smok Cessat. 2022 Jul 11;2022:2617146. doi: 10.1155/2022/2617146. eCollection 2022.

  PMID: 35909440 BACKGROUND

• Li X, Caulfield KA, Hartwell KJ, Henderson S, Brady KT, George MS. Reduced executive and reward connectivity is associated with smoking cessation response to repetitive transcranial magnetic stimulation: A double-blind, randomized, sham-controlled trial. Brain Imaging Behav. 2024 Feb;18(1):207-219. doi: 10.1007/s11682-023-00820-3. Epub 2023 Nov 23.

  PMID: 37996557 BACKGROUND

• Li X, Hartwell KJ, Owens M, Lematty T, Borckardt JJ, Hanlon CA, Brady KT, George MS. Repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex reduces nicotine cue craving. Biol Psychiatry. 2013 Apr 15;73(8):714-20. doi: 10.1016/j.biopsych.2013.01.003. Epub 2013 Feb 26.

  PMID: 23485014 RESULT

• Li X, Hartwell KJ, Henderson S, Badran BW, Brady KT, George MS. Two weeks of image-guided left dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation improves smoking cessation: A double-blind, sham-controlled, randomized clinical trial. Brain Stimul. 2020 Sep-Oct;13(5):1271-1279. doi: 10.1016/j.brs.2020.06.007. Epub 2020 Jun 10.

  PMID: 32534252 RESULT

• Li X, Caulfield KA, Carpenter MJ, Ramakrishnan V, Herrmann ES, Dancy M, George MS. DLPFC rTMS is more effective than sham or orbitofrontal stimulation for smoking cessation and alters frontal brain activity: A double-blind, sham-controlled randomized clinical trial. J Psychiatr Res. 2026 Jun;197:187-195. doi: 10.1016/j.jpsychires.2026.02.053. Epub 2026 Mar 4.

  PMID: 41793961 DERIVED

MeSH Terms

Conditions

Tobacco Use; Cigarette Smoking; Tobacco Use Disorder; Smoking Cessation

Condition Hierarchy (Ancestors)

Behavior; Tobacco Smoking; Smoking; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Health Behavior

Study Officials

• Xingbao Li, MD, MSCR, MS

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xingbao Li, MD, MSCR, MS

CONTACT

843-792-5729; lixi@musc.edu

Rebecca Keneally

CONTACT

843-792-0136; keneally@musc.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Sixty-four treatment-seeking TUDs between the ages of 22 and 70 will be randomly divided into two groups on a 1:1 basis (32 participants/condition). The first condition will receive E-sham rTMS and the other condition will receive active 10 Hz personalized-fMRI and E-field modeling guided rTMS (3000 pulses/session) over the left DLPFC.

Study Record Dates

• First Submitted: May 21, 2021
• First Posted: May 26, 2021
• Study Start: May 15, 2021
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): April 4, 2027
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)