dTMS for Smoking Cessation in Schizophrenia

Overseen By Scott J Moeller, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Stony Brook University

Must not be taking: Smoking cessation products, Clozapine

Disqualifiers: Substance use disorder, Epilepsy, Pregnancy, 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: 15

Duration: 3 weeks

38 Participants Needed

Trial Summary

What is the purpose of this trial?

Purpose of the study: Evaluate the effect of deep repetitive transcranial magnetic stimulation (deep rTMS; hereafter abbreviated as "dTMS") on synaptic density measured with positron emission tomography (PET) and the radiotracer \[11C\]UCB-J. The investigators also seek to link plasticity changes in the regions targeted by the electric field (especially, the insula) to changes in the functioning of insula circuits and behavioral cigarette usage in patients with schizophrenia (SCZ). Importance of the study: This is the first study designed to directly evaluate the mechanism of action (MOA) of dTMS for smoking disruption in patients with SCZ. Patients with SCZ are a vulnerable population in high, immediate need of new smoking therapeutics for reducing premature morbidity and mortality.

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 cannot participate if you've changed your schizophrenia medication in the last 4 weeks. Also, you cannot use smoking cessation medications during the study.

What data supports the effectiveness of the treatment for smoking cessation in schizophrenia?

Research suggests that high-frequency repetitive transcranial magnetic stimulation (rTMS) to the dorsolateral prefrontal cortex (DLPFC) can reduce tobacco craving and consumption in people with schizophrenia. Additionally, rTMS has shown potential in reducing relapse rates and increasing abstinence in smokers, indicating its promise as a treatment for smoking cessation. ^{1 2 3 4 5}

Is deep transcranial magnetic stimulation (dTMS) safe for humans?

Research shows that repetitive transcranial magnetic stimulation (rTMS), which is similar to dTMS, is generally safe for humans. Studies have used it for smoking cessation and other conditions, and it has been cleared by the US Food and Drug Administration for use in adults. ^{1 2 6 7 8}

How does the treatment dTMS for smoking cessation in schizophrenia differ from other treatments?

dTMS (deep transcranial magnetic stimulation) is unique because it targets specific brain areas like the insula and prefrontal cortex to reduce smoking cravings and consumption, which is different from traditional drug therapies. It uses magnetic fields to stimulate brain regions associated with addiction, offering a non-drug alternative for patients with schizophrenia who often struggle with smoking cessation. ^{1 2 4 6 9}

Eligibility Criteria

This trial is for English-speaking adults aged 18-60 with schizophrenia or related conditions who smoke daily and want to reduce or quit. They must be able to consent, have a negative drug test (except for cannabis), and meet DSM-5 criteria for nicotine use disorder.

Inclusion Criteria

I understand the information given to me and can make decisions about my health care.

I have been diagnosed with a schizophrenia spectrum disorder.

Negative urine toxicology (other than cannabis) maintained throughout study participation

Exclusion Criteria

I am currently using products to help me stop smoking.

Contraindications to dTMS*

I have a history of serious neurological issues or use medication that increases seizure risk.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive deep repetitive transcranial magnetic stimulation (dTMS) for 5 days a week over 3 weeks

3 weeks

15 visits (in-person)

Follow-up

Participants are monitored for changes in insula synaptic density and smoking behavior post-treatment

4 weeks

Treatment Details

Interventions

• Active deep transcranial magnetic stimulation (dTMS)
• Sham dTMS

Trial Overview The study tests if deep transcranial magnetic stimulation (dTMS) affects synaptic density in the brain's insula region, measured by PET scans, and if it influences smoking behavior in schizophrenia patients.

Participant Groups

Group I: Active deep transcranial magnetic stimulation (dTMS) Experimental Treatment 1 Intervention

Each treatment consists of 60 trains, each lasting 3 sec and interleaved with a 15 sec delay. The entire treatment is delivered over 20 min. The treatment goes for 5 days/week and for a total of 3 weeks.

Group II: Sham Placebo Group 1 Intervention

Active and sham cards do not differ in appearance, and both coils are enclosed within the same helmet, enabling double-blind administration. The same procedure will be done, the only difference is that the sham card does not deliver any stimulation.

Active deep transcranial magnetic stimulation (dTMS) is already approved in European Union, United States for the following indications:

Approved in European Union as Deep TMS for:

• Negative symptoms of schizophrenia

Approved in United States as rTMS for:

• Major depressive disorder
• Obsessive-compulsive disorder
• Smoking cessation

Who Is Running the Clinical Trial?

Stony Brook University

Lead Sponsor

Trials

225

Recruited

41,700+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Findings from Research

In a study involving 13 smokers with schizophrenia and 14 non-psychiatric controls, high-frequency repetitive transcranial magnetic stimulation (rTMS) did not significantly reduce tobacco craving or improve cognitive function after a short-term treatment period.

Despite the lack of efficacy in modifying craving and cognitive outcomes, the study found that rTMS was safe, with no significant adverse events reported, suggesting that further long-term studies are needed to explore its potential benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of short-term, high-frequency repetitive transcranial magnetic stimulation to bilateral dorsolateral prefrontal cortex on smoking behavior and cognition in patients with schizophrenia and non-psychiatric controls. Kozak, K., Sharif-Razi, M., Morozova, M., et al.[2021]

In a study involving 35 male schizophrenia patients, high-frequency rTMS (10Hz) over the left dorsolateral prefrontal cortex significantly reduced cigarette consumption compared to a sham treatment, with effects observed as early as the first week of stimulation.

The treatment did not correlate with changes in negative or depressive symptoms of schizophrenia, suggesting that rTMS specifically targets smoking behavior rather than overall psychiatric symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation reduces cigarette consumption in schizophrenia patients. Prikryl, R., Ustohal, L., Kucerova, HP., et al.[2017]

In a preliminary study involving 24 outpatients with schizophrenia and cannabis use disorder, high-frequency repetitive transcranial magnetic stimulation (rTMS) applied to the dorsolateral prefrontal cortex was found to be safe and well-tolerated, with a high retention rate of about 90%.

The active rTMS group showed a trend towards reduced cannabis use and craving, along with significant improvements in psychiatric symptoms and attention, suggesting that rTMS may be an effective treatment option for cannabis use disorder in patients with schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigating repetitive transcranial magnetic stimulation on cannabis use and cognition in people with schizophrenia. Bidzinski, KK., Lowe, DJE., Sanches, M., et al.[2022]

In a study involving 29 smokers, 8 sessions of 20Hz rTMS targeting the left dorsolateral prefrontal cortex significantly reduced delay discounting rates and decreased the risk of relapse by three-fold, indicating its potential efficacy in smoking cessation.

Participants receiving active rTMS had a higher abstinence rate of 50% compared to 15.4% in the sham group, suggesting that this treatment combined with a self-help intervention is both feasible and well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preventing relapse to smoking with transcranial magnetic stimulation: Feasibility and potential efficacy. Sheffer, CE., Bickel, WK., Brandon, TH., 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]

High dose transcranial magnetic stimulation (rTMS) at 10 Hz significantly reduced negative symptoms in schizophrenia patients, particularly blunted affect, emotional withdrawal, and passive/apathetic social withdrawal, with an effective rate of 43.75% compared to 11.43% in the control group.

While rTMS was found to be effective, it was associated with a higher incidence of headaches (37.50% in the study group) compared to the control group, indicating a need for monitoring side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effectiveness and safety of high dose transcranial magnetic stimulation in schizophrenia with refractory negative symptoms: a randomized controlled study]. Gan, J., Duan, H., Chen, Z., 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]

A study involving 20 patients with schizophrenia showed that bilateral deep repetitive transcranial magnetic stimulation (dTMS) significantly delayed the initiation of smoking compared to a sham treatment, indicating its potential to disrupt tobacco self-administration.

Imaging results suggested that active dTMS led to decreased blood flow in the insula and changes in brain connectivity, hinting at its mechanism of action and possible therapeutic effects on psychotic symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep rTMS of the insula and prefrontal cortex in smokers with schizophrenia: Proof-of-concept study. Moeller, SJ., Gil, R., Weinstein, JJ., et al.[2022]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of short-term, high-frequency repetitive transcranial magnetic stimulation to bilateral dorsolateral prefrontal cortex on smoking behavior and cognition in patients with schizophrenia and non-psychiatric controls. [2021]

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

Repetitive transcranial magnetic stimulation reduces cigarette consumption in schizophrenia patients. [2017]

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

Investigating repetitive transcranial magnetic stimulation on cannabis use and cognition in people with schizophrenia. [2022]

4. Ireland pubmed.ncbi.nlm.nih.gov

Preventing relapse to smoking with transcranial magnetic stimulation: Feasibility and potential efficacy. [2022]

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

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

6. England pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation for Tobacco Treatment in Cancer Patients: A Preliminary Report of a One-Week Treatment. [2022]

7. China pubmed.ncbi.nlm.nih.gov

[Effectiveness and safety of high dose transcranial magnetic stimulation in schizophrenia with refractory negative symptoms: a randomized controlled study]. [2018]

8. Italy pubmed.ncbi.nlm.nih.gov

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

9. Germany pubmed.ncbi.nlm.nih.gov

Deep rTMS of the insula and prefrontal cortex in smokers with schizophrenia: Proof-of-concept study. [2022]