TMS + Counseling + Nicotine Replacement for Smoking Cessation

(TMS-STOP Trial)

Overseen By Angela C Kirby, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: VA Office of Research and Development

Must be taking: Nicotine replacement

Must not be taking: Bupropion, Varenicline

Disqualifiers: Substance use disorder, Seizures, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 10

Duration: 1 week

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to help Veterans with PTSD quit smoking. It combines counseling, nicotine replacement (such as nicotine gum), and a brain stimulation technique called repetitive transcranial magnetic stimulation (rTMS). The goal is to evaluate how effectively these treatments work together to aid smoking cessation. Veterans who smoke at least 10 cigarettes a day and wish to quit may be suitable for this study. The trial includes two groups: one receives real rTMS, while the other receives a sham version for comparison. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant findings.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not be currently prescribed bupropion or varenicline. You also need to have been stable on any psychotropic medications for at least three months.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) is generally safe for people trying to quit smoking. Several studies found rTMS to be as safe as other smoking cessation methods, such as medication or nicotine patches, meaning it typically doesn't cause more side effects than these treatments.

One study tested rTMS on cancer patients who wanted to quit smoking and found it safe. In one instance, a participant reported back pain after a placebo treatment but recovered quickly. Overall, these studies indicate that rTMS is well-tolerated, with no major safety concerns reported. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using repetitive transcranial magnetic stimulation (rTMS) combined with cognitive behavioral therapy (CBT) and nicotine replacement for smoking cessation because it offers a unique approach compared to traditional methods like nicotine patches or medications. Unlike most treatments that primarily focus on managing withdrawal symptoms, rTMS targets brain activity directly. This method uses magnetic fields to stimulate nerve cells in the brain, potentially reducing cravings and improving self-control. By addressing the neurological aspects of addiction, this combination could provide a more comprehensive solution for those struggling to quit smoking.

What evidence suggests that this trial's treatments could be effective for smoking cessation in Veterans with PTSD?

Research has shown that repetitive transcranial magnetic stimulation (rTMS), which participants in this trial may receive, can help people stop smoking. One study found that individuals who underwent 15 sessions of real rTMS were more likely to quit than those who received a sham treatment. Another study discovered that rTMS helped reduce the number of cigarettes smoked daily. This treatment uses magnets to stimulate the brain, potentially lessening nicotine cravings. Overall, rTMS appears to be a promising tool to support smoking cessation efforts. ^{1 2 4 6 7}

Who Is on the Research Team?

Jonathan R Young, MD

Principal Investigator

Durham VA Medical Center, Durham, NC

Are You a Good Fit for This Trial?

This trial is for US Veterans aged 18-75 who smoke at least 10 cigarettes daily, have PTSD, and are stable on psychotropic meds. They must speak English and be willing to try quitting smoking. Excluded are those with brain lesions, recent substance abuse (other than tobacco), heart attack risks, seizure history, certain implanted devices or metals in the head, pregnancy, inability to consent or complete procedures.

Inclusion Criteria

Is a US Veteran

Meets DSM-5 criteria for tobacco use disorder

Smokes an average of 10 cigarettes per day for the past 6 months, with carbon monoxide (CO) level > 6 ppm

Exclusion Criteria

Implanted devices that may be affected by MRI or TMS (pacemaker, medication pump, cochlear implant, implanted deep brain stimulator)

I or someone in my family has had seizures or epilepsy.

I have a history of brain conditions that could increase my risk of seizures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Treatment Neuroimaging

Participants undergo resting-state functional magnetic resonance imaging (rs-fMRI) before the rTMS treatment

1 week

1 visit (in-person)

Treatment

Participants receive a 5-day course of neuronavigated rTMS in conjunction with nicotine replacement therapy (NRT) and cognitive behavioral therapy (CBT)

1 week

5 visits (in-person)

Post-Treatment Neuroimaging

Participants undergo post-treatment rs-fMRI to assess changes in functional network connectivity

1 week

1 visit (in-person)

Follow-up

Participants are monitored for smoking cessation outcomes and safety, including self-reported cravings and withdrawal symptoms

5 weeks

2 visits (in-person)

3-Month Follow-up

Participants are assessed for long-term smoking cessation outcomes and retention

3 months

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Cognitive Behavioral Therapy for Smoking Cessation
• Nicotine Replacement Therapy
• Repetitive Transcranial Magnetic Stimulation (rTMS)

Trial Overview The study tests if combining counseling for smoking cessation with nicotine replacement therapy (like nicotine gum) and repetitive transcranial magnetic stimulation (rTMS)—a noninvasive brain treatment—helps veterans quit smoking more effectively than current methods.

How Is the Trial Designed?

Group I: active rTMS Experimental Treatment 3 Interventions

Participants assigned to this group will receive active repetitive transcranial magnetic stimulation (rTMS) as part of their smoking cessation treatment.

Group II: sham rTMS Placebo Group 3 Interventions

Participants assigned to this group will receive sham repetitive transcranial magnetic stimulation (rTMS) as part of their smoking cessation treatment.

Cognitive Behavioral Therapy for Smoking Cessation is already approved in United States, European Union for the following indications:

Approved in United States as Cognitive Behavioral Therapy for Smoking Cessation for:

• Smoking cessation

Approved in European Union as Cognitive Behavioral Therapy for Smoking Cessation for:

• Smoking cessation

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Published Research Related to This Trial

In a pilot study involving 11 tobacco-dependent smokers, repetitive transcranial magnetic stimulation (rTMS) significantly reduced cravings for tobacco compared to placebo, suggesting its potential as a therapeutic intervention.

Given that traditional smoking cessation methods have low long-term success rates, rTMS may offer a new approach to help increase abstinence rates among smokers who want to quit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Repetitiv Transcranial Magnetic Stimulation in Nicotine Dependence] Johann, M., Wiegand, R., Kharraz, A., et al.[2019]

A multicenter double-blind RCT involving 262 chronic smokers showed that repetitive transcranial magnetic stimulation (rTMS) significantly increased the continuous quit rate (CQR) to 19.4% compared to 8.7% for the sham treatment, indicating its efficacy in promoting smoking cessation.

This study established a safe treatment protocol for rTMS, which has now received FDA clearance as an aid for smoking cessation, marking a significant advancement in addiction medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation for smoking cessation: a pivotal multicenter double-blind randomized controlled trial. Zangen, A., Moshe, H., Martinez, D., et al.[2021]

A pilot study involving 11 tobacco-dependent smokers found that repetitive transcranial magnetic stimulation (rTMS) significantly reduced cravings for tobacco compared to a placebo, suggesting its potential as a therapeutic intervention.

Given that traditional smoking cessation methods have low success rates (around 30% abstinence after 12 months), rTMS may offer a promising alternative to help increase tobacco abstinence rates in smokers looking to quit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Transcranial magnetic stimulation for nicotine dependence]. Johann, M., Wiegand, R., Kharraz, A., et al.[2014]

In a study of 23 participants, repetitive transcranial magnetic stimulation (rTMS) targeting the left dorsolateral prefrontal cortex showed that increasing the duration of treatment significantly improved the odds of smoking abstinence by 7-8 times, while increasing the intensity of sessions doubled the odds.

The research suggests that delay discounting rates, which relate to impulsivity in decision-making, could be a valuable target for smoking cessation therapies, with both duration and intensity of rTMS treatment contributing to better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Magnetic Stimulation for Long-Term Smoking Cessation: Preliminary Examination of Delay Discounting as a Therapeutic Target and the Effects of Intensity and Duration. Shevorykin, A., Carl, E., Mahoney, MC., et al.[2022]

In a study of 37 smokers with severe nicotine dependence, combining 1-Hz repetitive Transcranial Magnetic Stimulation (rTMS) with Nicotine Replacement Therapy (NRT) significantly increased abstinence rates, with 16 out of 18 participants in the active rTMS group remaining abstinent compared to 9 out of 19 in the sham group.

Active rTMS also led to a significant reduction in craving levels, particularly in the compulsive aspect of cravings, suggesting that rTMS may help manage withdrawal symptoms during smoking cessation, although the effects did not persist long-term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Magnetic Stimulation Combined With Nicotine Replacement Therapy for Smoking Cessation: A Randomized Controlled Trial. Trojak, B., Meille, V., Achab, S., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8429333/

Repetitive transcranial magnetic stimulation for smoking ... In that study, 15 active rTMS sessions (20 min/weekday for three weeks), compared to sham, induced a significantly higher quit rate and reduced ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165178123002901

Repetitive transcranial magnetic stimulation for smoking ... At 2 weeks, abstinence rates are low at only 32% (Agboola et al., 2015), which is important given that discontinuation rates are high early in the treatment ...

3. mecp.springeropen.com mecp.springeropen.com/articles/10.1186/s43045-025-00558-2

Efficacy of repetitive transcranial magnetic stimulation for ... Conclusion. rTMS shows promising potential as an adjunctive treatment for smoking cessation by reducing nicotine dependence (to some extent) and ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9293555/

Repetitive Transcranial Magnetic Stimulation for Tobacco ... Brains way announces successful results in pivotal multicenter study evaluating deep transcranial magnetic stimulation system as an aid in smoking cessation.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0163834325001070

Effectiveness and safety of repeated transcranial magnetic ... The meta-analysis showed that, comparing with the control group, active rTMS significantly decreased the average daily number of cigarettes smoked (MD = −6.72, ...

6. mecp.springeropen.com mecp.springeropen.com/articles/10.1186/s43045-025-00503-3

Efficacy and safety of repetitive transcranial magnetic ... This study aimed to assess the effectiveness of active r-TMS in reducing smoking behavior, withdrawal symptoms, cravings, and nicotine dependence

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06346028?term=AREA%5BBasicSearch%5D(brainsway)&rank=7

Implementation of Transcranial Magnetic Stimulation for ... A landmark 2021 study showed that daily rTMS treatment for 6 weeks targeting these regions is effective at reducing craving and cigarette use. This study's ...