rTMS for Reducing Smoking Cravings

Overseen By Mariya V Cherkasova, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: West Virginia University

Must not be taking: Antidepressants, Antipsychotics, Amphetamines, others

Disqualifiers: Epilepsy, Stroke, Brain lesions, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 3-6 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

The objective of this pilot clinical trial is to test the effects of different types of thinking strategies at the time of repetitive Transcranial Magnetic Stimulation (rTMS), applied to the left Dorsolateral Prefrontal Cortex (DLPFC), on smoking craving and brain activity. Participants will be individuals with moderate to high smoking dependence (smoking at least 8 cigarettes a day) who have no intention of quitting in the next 3 months and are eligible to have rTMS and functional magnetic resonance imaging (fMRI). The main objectives of the trial are: 1. To compare the craving-reducing effects of "upregulation" and "downregulation" of craving while looking at pictures related to cigarette smoking during rTMS versus no regulation of craving while looking at neutral pictures unrelated to smoking. 'Upregulation" is thinking about the immediate positive experience of smoking. "Downregulation" is thinking about the long-term negative consequences of smoking. 2. To examine changes in brain activity that accompany craving reductions produced by rTMS paired with upregulation and downregulation of craving while looking at pictures related to cigarette smoking versus no regulation of craving while looking at neutral pictures unrelated to smoking. Following screening for eligibility, participants will be trained on how to do upregulation and downregulation of craving. The participants will then participate in 3 testing sessions. In each session, the participants will receive rTMS at 20Hz in 50 trains (2000 pulses total), followed immediately by fMRI. Sessions will take place 1-2 weeks apart and will differ in the type of thinking strategy participants will use while looking at pictures during the rTMS: * upregulation of craving while viewing smoking-related images * downregulation of craving while viewing smoking-related images * no regulation of craving while viewing neutral smoking-unrelated images The order of sessions will be randomized across participants.

Do I need to stop my current medications to join the trial?

The trial requires you to stop certain medications that lower the seizure threshold, such as some antidepressants and recreational drugs. If you're on varenicline or nicotine replacement therapy, you cannot participate. The protocol doesn't specify other medications, but it's best to discuss with the trial team.

Will I have to stop taking my current medications?

The trial requires that you do not take certain medications that lower the seizure threshold, such as some antidepressants and recreational drugs. If you are currently using varenicline or nicotine replacement therapy, you will need to stop these before participating.

What data supports the idea that rTMS for Reducing Smoking Cravings is an effective treatment?

The available research shows that rTMS can effectively reduce smoking cravings and help people quit smoking. One study found that after receiving rTMS, 19.4% of participants were able to quit smoking for four weeks, compared to only 8.7% who received a fake treatment. Another study showed that rTMS reduced the desire to smoke when people were exposed to smoking-related cues. These results suggest that rTMS can be a helpful treatment for reducing smoking cravings and supporting smoking cessation. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment rTMS-concurrent Behavioral Priming, Repetitive Transcranial Magnetic Stimulation, rTMS for reducing smoking cravings?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can help reduce cigarette cravings and consumption by stimulating specific areas of the brain. In a large study, smokers who received rTMS were more successful in quitting smoking compared to those who received a fake treatment, with a higher quit rate and reduced cravings. ^{1 2 3 4 5}

What safety data exists for rTMS in reducing smoking cravings?

The provided research abstracts do not explicitly mention safety data for rTMS in reducing smoking cravings. They focus on the effectiveness of rTMS in reducing cravings and cigarette consumption, as well as its impact on brain activity. For specific safety data, further investigation into detailed study results or reviews focusing on safety and side effects would be necessary. ^{2 3 4 5 6}

Is rTMS safe for humans?

Repetitive transcranial magnetic stimulation (rTMS) is generally considered safe for humans, as it noninvasively stimulates the brain and has been used in various studies without major safety concerns. ^{2 3 4 5 6}

Is the treatment rTMS-concurrent Behavioral Priming a promising treatment for reducing smoking cravings?

Yes, rTMS, which is a treatment that uses magnetic pulses to stimulate the brain, shows promise in reducing smoking cravings. Studies have found that it can decrease the desire to smoke and reduce cigarette consumption by targeting specific brain areas related to craving. ^{2 3 4 5 7}

How is the rTMS treatment for reducing smoking cravings different from other treatments?

The rTMS treatment is unique because it uses magnetic pulses to noninvasively stimulate specific areas of the brain, like the dorsolateral prefrontal cortex, to reduce cravings for cigarettes. Unlike medications or behavioral therapies, rTMS directly targets brain activity related to craving, offering a novel approach to managing smoking addiction. ^{2 3 4 5 7}

Research Team

Mariya V Cherkasova, PhD

Principal Investigator

West Virginia University

Eligibility Criteria

This trial is for individuals who smoke at least 8 cigarettes daily, have no plans to quit in the next 3 months, and can safely undergo rTMS and fMRI. It's not specified who cannot participate, but typically those with metal implants or certain medical conditions may be excluded.

Inclusion Criteria

Able to provide written informed consent, and to follow study procedures

Dual use of cigarettes and e-cigarettes is permitted

Active cigarette smoker consuming at least 8 cigarettes a day for at least 6 months

Exclusion Criteria

Pregnancy

I have had a serious head injury in the past.

I may have a mental health condition based on a specific questionnaire score.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Training

Participants are trained on how to do upregulation and downregulation of craving

1 week

Treatment

Participants undergo 3 testing sessions with rTMS and fMRI, using different thinking strategies

3-6 weeks

3 visits (in-person)

Follow-up

Participants are monitored for changes in smoking cravings and brain activity

1 week

Treatment Details

Interventions

• rTMS-concurrent Behavioral Priming

Trial Overview The study tests how different thinking strategies during rTMS affect smoking cravings and brain activity. Participants will try 'upregulation' (focusing on positive smoking experiences) and 'downregulation' (considering negative consequences) while viewing related images during sessions.

Participant Groups

Group I: Active rTMS Experimental Treatment 1 Intervention

There is a single arm in this open-label pilot study. All participants will receive active rTMS paired with different types of behavioral priming (upregulation of craving, downregulation of craving, no regulation of craving).

rTMS-concurrent Behavioral Priming is already approved in United States for the following indications:

Approved in United States as rTMS for:

• Smoking cessation

Who Is Running the Clinical Trial?

West Virginia University

Lead Sponsor

Trials

192

Recruited

64,700+

Findings from Research

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 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]

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]

A single session of repetitive transcranial magnetic stimulation (rTMS) applied to the dorsolateral prefrontal cortex (DLPFC) significantly reduced brain activity in areas associated with craving, specifically the medial orbitofrontal cortex (mOFC) and nucleus accumbens (NAc), in a study of 11 nicotine-dependent smokers.

These results suggest that rTMS may help decrease craving in smokers by modulating neural activity in key brain regions, indicating a potential mechanism for its anti-craving effects and supporting further research in addiction treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation of the dorsal lateral prefrontal cortex inhibits medial orbitofrontal activity in smokers. Li, X., Sahlem, GL., Badran, BW., et al.[2018]

A single session of repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex significantly reduces brain activity in the right insula and thalamus in non-treatment-seeking smokers, suggesting a potential mechanism for reducing craving.

The study, involving 10 nicotine-dependent smokers, also found that rTMS decreased connectivity between the left dorsolateral prefrontal cortex and the medial orbitofrontal cortex, indicating changes in brain networks related to craving and addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Li, X., Du, L., Sahlem, GL., et al.[2018]

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]

In a study involving 15 smokers, high-frequency rTMS (10 Hz) applied to the superior frontal gyrus (SFG) increased craving responses to smoking cues while reducing cravings for neutral cues, indicating a dual role of the SFG in craving modulation.

The findings suggest that the SFG can both enhance and inhibit craving responses, supporting its involvement in the brain's regulation of drug-seeking behaviors, which could inform future treatments for smoking cessation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation of the superior frontal gyrus modulates craving for cigarettes. Rose, JE., McClernon, FJ., Froeliger, B., et al.[2022]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation for smoking cessation: a pivotal multicenter double-blind randomized controlled trial. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Repeated high-frequency transcranial magnetic stimulation over the dorsolateral prefrontal cortex reduces cigarette craving and consumption. [2022]

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

Repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex reduces nicotine cue craving. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation of the dorsal lateral prefrontal cortex inhibits medial orbitofrontal activity in smokers. [2018]

5. Ireland pubmed.ncbi.nlm.nih.gov

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. [2018]

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

Transcranial Magnetic Stimulation Combined With Nicotine Replacement Therapy for Smoking Cessation: A Randomized Controlled Trial. [2018]

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

Repetitive transcranial magnetic stimulation of the superior frontal gyrus modulates craving for cigarettes. [2022]