rTMS for Smoking Cessation

Overseen By Xingbao Li, MD, MSCR, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medical University of South Carolina

Disqualifiers: Substance use, Neurological disorders, Axis I, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 25

Duration: 4 weeks

64 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether transcranial magnetic stimulation (TMS), a form of brain stimulation, can help people quit smoking. TMS is a non-invasive therapy using magnets to influence brain activity and has shown promise in treating depression and smoking habits. Participants will receive either the active TMS treatment or a sham (placebo) version to compare effectiveness. The study seeks individuals who smoke at least 10 cigarettes a day, wish to quit, and are in stable mental and physical health. As an unphased trial, it offers a unique opportunity to contribute to innovative research that could lead to new smoking cessation therapies.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it does exclude those with moderate to severe substance use of psychoactive substances other than nicotine or caffeine.

What prior data suggests that this technique is safe for smoking cessation?

Studies have shown that repetitive transcranial magnetic stimulation (rTMS) is generally safe for helping people quit smoking. Research suggests that rTMS targets specific brain areas to reduce smoking without causing major problems. A review of several studies found that rTMS is well-tolerated, with no serious side effects reported. Other studies support these findings, showing that participants experienced only minor side effects, such as mild headaches or scalp discomfort. Overall, rTMS appears to be a safe option for those looking to quit smoking. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using repetitive Transcranial Magnetic Stimulation (rTMS) for smoking cessation because it offers a non-invasive approach that targets the brain's prefrontal cortex. Unlike traditional methods such as nicotine replacement therapy or medications like varenicline, rTMS uses magnetic fields to stimulate specific brain areas associated with addiction. This technique could potentially reduce cravings and withdrawal symptoms without the side effects linked to current pharmacological treatments. Additionally, the precision of targeting the dorsolateral prefrontal cortex (DLPFC) with a 10 Hz frequency could lead to more effective and faster results in helping individuals quit smoking.

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

Research has shown that repetitive transcranial magnetic stimulation (rTMS) may help people quit smoking. In this trial, participants may receive either Active rTMS 10 Hz DLPFC or Sham rTMS. Some studies suggest that rTMS can lower nicotine dependence, a major hurdle in quitting. The focus has been on using 10 Hz rTMS on the left dorsolateral prefrontal cortex (DLPFC), a brain area involved in decision-making and self-control. This method has helped some participants reduce cravings and withdrawal symptoms. Overall, while research continues, rTMS offers a non-drug option that might assist those trying to stop smoking. ^{6 7 8 9 10}

Who Is on the Research Team?

Xingbao Li, M.D

Principal Investigator

Medical University of South Carolina

Are You a Good Fit for This Trial?

This trial is for adults aged 18-60 who smoke at least 10 cigarettes daily, want to quit smoking, and are in stable health. They must not have had substance abuse treatment recently or use other nicotine products. Pregnant women or those with certain medical conditions like severe heart disease, brain lesions, or metal implants that interfere with MRI scans cannot participate.

Inclusion Criteria

Meet the criteria for tobacco use disorder as determined by DSM-5

Smoke 10 or more cigarettes per day and have a carbon monoxide (CO) level > 10 ppm indicative of recent smoking

I am not pregnant and use reliable birth control methods.

Exclusion Criteria

I have a history of brain-related autoimmune, endocrine, viral, or vascular disorders.

I do not have severe heart, kidney, liver problems, or uncontrolled high blood pressure.

Current moderate to severe substance use of any psychoactive substances other than nicotine or caffeine, as defined by DSM-V criteria

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 20 daily sessions of rTMS over 4 weeks, with functional MRI scans performed before the first TMS treatment, after session 10, and after the last session.

4 weeks

20 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with follow-up visits at 1 week, 1 month, 2 months, 3 months, and 4 months after the last TMS session.

16 weeks

5 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Active rTMS 10 Hz DLPFC
• Active rTMS 1 Hz mOFC
• Sham rTMS

Trial Overview

The study tests if rTMS (a non-invasive brain stimulation) can help people stop smoking. Participants will receive either sham (fake) rTMS or active rTMS targeted at specific brain areas using MRI guidance to potentially reduce their craving for cigarettes.

How Is the Trial Designed?

Group I: Active rTMS 10 Hz DLPFC Active Control 1 Intervention

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.

Group II: Sham rTMS Placebo Group 1 Intervention

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.

Active rTMS 10 Hz DLPFC is already approved in United States, Canada for the following indications:

Approved in United States as rTMS for:

• Short-term smoking cessation

Approved in Canada as rTMS for:

• Smoking cessation

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

This study involves 258 adults motivated to quit smoking and aims to determine the optimal dosing strategy for high frequency repetitive transcranial magnetic stimulation (rTMS) to enhance long-term abstinence from smoking while minimizing side effects.

The research will assess various outcomes, including relapse rates and cognitive-behavioral skills, over a 6-month follow-up period, potentially paving the way for innovative treatments for tobacco dependence and other addictions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosing parameters for the effects of high-frequency transcranial magnetic stimulation on smoking cessation: study protocol for a randomized factorial sham-controlled clinical trial. Carl, E., Liskiewicz, A., Rivard, C., et al.[2021]

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]

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]

In a study of 40 chronic cigarette smokers, 10 daily sessions of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) over the left dorsolateral prefrontal cortex significantly reduced cigarette consumption and cravings, with effects lasting up to 3 months after treatment.

HF-rTMS also led to significant improvements in symptoms of anxiety and depression, as measured by the Hamilton scales, indicating that this treatment may benefit both smoking addiction and mental health in the same individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind randomized clinical trial of high frequency rTMS over the DLPFC on nicotine dependence, anxiety and depression. Abdelrahman, AA., Noaman, M., Fawzy, M., et al.[2021]

In a study involving 48 chronic smokers, ten daily sessions of high-frequency transcranial magnetic stimulation (rTMS) on the left dorsolateral prefrontal cortex significantly reduced cigarette consumption and nicotine dependence.

The rTMS treatment also effectively blocked cravings triggered by smoking-related cues, although the benefits appeared to decrease over time after the treatment ended.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repeated high-frequency transcranial magnetic stimulation over the dorsolateral prefrontal cortex reduces cigarette craving and consumption. Amiaz, R., Levy, D., Vainiger, D., et al.[2022]

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]

A pilot study involving 24 participants with severe nicotine dependence showed that 1 Hz repetitive transcranial magnetic stimulation (rTMS) over the left frontal pole significantly reduced craving responses to both smoking-related and neutral cues, indicating its potential efficacy in treating tobacco use disorder.

The study found a correlation between improved verbal memory recall and reduced reactivity to neutral cues, suggesting that rTMS may influence craving experiences through its effects on memory systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left frontal pole repetitive transcranial magnetic stimulation reduces cigarette cue-reactivity in correlation with verbal memory performance. Marques, RC., Marques, D., Vieira, L., et al.[2022]

A single session of high-frequency rTMS (10 Hz) over the left dorsolateral prefrontal cortex significantly reduced cigarette craving in 16 nicotine-dependent participants, demonstrating its potential efficacy as a noninvasive treatment.

The reduction in craving was notably greater with real rTMS compared to sham treatment, suggesting that rTMS may be a promising tool for aiding smoking cessation efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex reduces nicotine cue craving. Li, X., Hartwell, KJ., Owens, M., et al.[2022]

In a study involving 11 cancer patients who smoke, 5 sessions of repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex showed modest reductions in cigarette consumption and significant decreases in craving, indicating potential efficacy for smoking cessation.

No serious side effects were reported from the rTMS treatment, suggesting it is a safe option for cancer patients seeking to quit smoking, although more research is needed to confirm its effectiveness and safety in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation for Tobacco Treatment in Cancer Patients: A Preliminary Report of a One-Week Treatment. Li, X., Toll, BA., Carpenter, MJ., et al.[2022]

In a study involving 42 treatment-seeking smokers, 10 sessions of repetitive transcranial magnetic stimulation (rTMS) significantly reduced daily cigarette consumption by 62.93% compared to a 39.43% reduction with sham treatment, indicating its efficacy in tobacco use disorders.

fMRI results showed that rTMS increased activity in brain areas associated with executive control (dorsal anterior cingulate cortex and DLPFC) while decreasing activity in reward-related areas (medial orbitofrontal cortex), suggesting a mechanism of action that enhances self-control and reduces craving.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced executive and reward connectivity is associated with smoking cessation response to repetitive transcranial magnetic stimulation: A double-blind, randomized, sham-controlled trial. Li, X., Caulfield, KA., Hartwell, KJ., et al.[2023]

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