TMS + Counseling + Nicotine Replacement for Smoking Cessation

(TMS-STOP Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Jonathan R Young, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Prior Safety Data

Trial Summary

What is the purpose of this trial?

Tobacco use is the number one preventable cause of the death in the United States, and is high among US Veterans, and those who have experienced trauma are more likely to smoke. Despite the efficacy of current evidence-based treatments for smoking cessation, there is a critical need for alternative treatments. This project seeks to evaluate the feasibility and effectiveness of a smoking cessation treatment for Veterans with posttraumatic stress disorder (PTSD) who smoke. The treatment combines smoking cessation counseling, nicotine replacement therapy (e.g., nicotine gum), and repetitive transcranial magnetic stimulation (rTMS). rTMS is a noninvasive brain stimulation treatment that has been cleared by the Food and Drug Administration for smoking cessation in adults.

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.

What data supports the effectiveness of this treatment for smoking cessation?

Research shows that repetitive Transcranial Magnetic Stimulation (rTMS), when combined with Nicotine Replacement Therapy (NRT), can significantly reduce tobacco cravings and increase quit rates among smokers. In a large study, smokers receiving active rTMS had higher quit rates compared to those receiving a placebo, suggesting that rTMS can be a helpful tool in smoking cessation.

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Is the combination of TMS, counseling, and nicotine replacement safe for smoking cessation?

Research shows that repetitive transcranial magnetic stimulation (rTMS) is generally safe and has been used in treating psychiatric disorders like depression. A large study confirmed its safety for smoking cessation, leading to FDA clearance for this use.

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How is the TMS + Counseling + Nicotine Replacement treatment for smoking cessation different from other treatments?

This treatment is unique because it combines repetitive Transcranial Magnetic Stimulation (rTMS), a non-invasive brain stimulation technique, with counseling and nicotine replacement therapy. rTMS targets brain areas involved in addiction and craving, potentially enhancing the effectiveness of traditional smoking cessation methods.

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Eligibility Criteria

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

I am between 18 and 75 years old.

Is a US Veteran

Meets DSM-5 criteria for tobacco use disorder

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.

Trial Timeline

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)

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Durham VA Medical Center, Durham, NC Durham, NC

Who Is Running the Clinical Trial?

VA Office of Research and Development Lead Sponsor

References

1. Germany pubmed.ncbi.nlm.nih.gov

[Repetitiv Transcranial Magnetic Stimulation in Nicotine Dependence] [2019] 70 - 80 % of regular smokers fulfill the ICD-10-criteria of dependence. In Germany, approximately 120 000 deaths per year are caused by tobacco-associated diseases. In contrast, therapeutic interventions, such as nicotine substitution or bupropione, yield poor abstinence rates of 30 % after 12 months, at best. In animal experiments, repetitive transcranial magnetic stimulation (rTMS) exhibited modulatory effects on dopaminergic neurotransmission in regions of the so-called reward system. This pilot study should evaluate, if rTMS could modulate subjective craving for tobacco, which quite often leads to relapse to smoking. Therefore, 11 tobacco-dependent cigarette smokers were randomly assigned to a course of verum- and placebo-rTMS on consecutive days. Craving, as measured by a visual analogue scale, is significantly decreased after Verumstimulation compared to placebostimulation intra-individually. This encourages further studies to clarify, if rTMS might be helpful in achieving higher tobacco abstinence rates in smokers willing to quits.

2. United States pubmed.ncbi.nlm.nih.gov

Transcranial Magnetic Stimulation Combined With Nicotine Replacement Therapy for Smoking Cessation: A Randomized Controlled Trial. [2018] Further evidence suggests that repetitive Transcranial Magnetic Stimulation (rTMS) is an effective method to reduce tobacco craving among smokers.

3. Germany pubmed.ncbi.nlm.nih.gov

[Transcranial magnetic stimulation for nicotine dependence]. [2014] 70-80% of regular smokers fulfill the ICD-10-criteria of dependence. In Germany, approximately 120,000 deaths per year are caused by tobacco-associated diseases. In contrast, therapeutic interventions, such as nicotine substitution or bupropione, yield poor abstinence rates of 30% after 12 months, at best. In animal experiments, repetitive transcranial magnetic stimulation (rTMS) exhibited modulatory effects on dopaminergic neurotransmission in regions of the so-called reward system. This pilot study should evaluate, if rTMS could modulate subjective craving for tobacco, which quite often leads to relapse to smoking. Therefore, 11 tobacco-dependent cigarette smokers were randomly assigned to a course of verum- and placebo-rTMS on consecutive days. Craving, as measured by a visual analogue scale, is significantly decreased after Verumstimulation compared to placebo-stimulation intra-individually. This encourages further studies to clarify, if rTMS might be helpful in achieving higher tobacco abstinence rates in smokers willing to quits.

4. Italy pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation for smoking cessation: a pivotal multicenter double-blind randomized controlled trial. [2021] Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation method increasingly used to treat psychiatric disorders, primarily depression. Initial studies suggest that rTMS may help to treat addictions, but evaluation in multicenter randomized controlled trials (RCTs) is needed. We conducted a multicenter double-blind RCT in 262 chronic smokers meeting DSM-5 criteria for tobacco use disorder, who had made at least one prior failed attempt to quit, with 68% having made at least three failed attempts. They received three weeks of daily bilat-eral active or sham rTMS to the lateral prefrontal and insular cortices, followed by once weekly rTMS for three weeks. Each rTMS session was administered following a cue-induced craving procedure, and participants were monitored for a total of six weeks. Those in abstinence were monitored for additional 12 weeks. The primary outcome measure was the four-week continuous quit rate (CQR) until Week 18 in the intent-to-treat efficacy set, as determined by daily smoking diaries and verified by urine cotinine measures. The trial was registered at ClinicalTrials.gov (NCT02126124). In the intent-to-treat analysis set (N=234), the CQR until Week 18 was 19.4% following active and 8.7% following sham rTMS (X2 =5.655, p=0.017). Among completers (N=169), the CQR until Week 18 was 28.0% and 11.7%, respectively (X2 =7.219, p=0.007). The reduction in cigarette consumption and craving was significantly greater in the active than the sham group as early as two weeks into treatment. This study establishes a safe treatment protocol that promotes smoking cessation by stimulating relevant brain circuits. It represents the first large multicenter RCT of brain stimulation in addiction medicine, and has led to the first clearance by the US Food and Drug Administration for rTMS as an aid in smok-ing cessation for adults.

5. Switzerland 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. [2022] Repetitive transcranial magnetic stimulation (rTMS) is a novel treatment for smoking cessation and delay discounting rate is novel therapeutic target. Research to determine optimal therapeutic targets and dosing parameters for long-term smoking cessation is needed. Due to potential biases and confounds introduced by the COVID-19 pandemic, we report preliminary results from an ongoing study among participants who reached study end prior to the pandemic.