Brain Stimulation for Nicotine Addiction in Schizophrenia

Recruiting in Palo Alto (17 mi)

Overseen by Heather B Ward, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Vanderbilt University Medical Center

Must not be taking: CNS active drugs

Disqualifiers: Intellectual disability, Substance use disorder, Neurologic disorder, others

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to compare two active types of transcranial magnetic stimulation in two nicotine-using populations: nicotine-using people with psychosis and nicotine-using people without a diagnosis of a psychotic disorder. The main questions it aims to answer are: 1. Can rTMS change functional connectivity in brain circuits associated with nicotine use? 2. Are those rTMS-induced changes in functional connectivity related to craving? Participants will complete tasks assessing their cognitive performance and craving before and after each week of TMS. Researchers will compare the effect of each TMS intervention on participants with and without psychosis to see if one type of TMS has an effect on nicotine craving.

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

The trial protocol does not specify if you need to stop your current medications. However, your medications will be reviewed by a physician, and a decision will be made based on your medical history and medication details.

What data supports the effectiveness of the treatment Network-Targeted Neuromodulation, Transcranial Magnetic Stimulation, rTMS, Network-Targeted Neuromodulation for nicotine addiction in schizophrenia?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can reduce tobacco cravings and consumption in people with schizophrenia, although results are mixed. In general, rTMS has been effective for smoking cessation in the general population, and it is FDA-approved for this purpose. ^{1 2 3 4 5}

Is brain stimulation safe for treating nicotine addiction in people with schizophrenia?

Repetitive transcranial magnetic stimulation (rTMS) is generally considered safe and is already FDA-approved for smoking cessation in adults. Studies have shown it can reduce cigarette consumption and craving, and it has been used safely in people with schizophrenia, although results can vary. ^{1 2 3 5 6}

How is the treatment Network-Targeted Neuromodulation different from other treatments for nicotine addiction in schizophrenia?

Network-Targeted Neuromodulation, or repetitive Transcranial Magnetic Stimulation (rTMS), is unique because it uses magnetic fields to stimulate specific areas of the brain, like the dorsolateral prefrontal cortex, to reduce tobacco cravings and consumption. Unlike traditional medications, this non-invasive treatment directly targets brain circuits involved in addiction, offering a novel approach for those with schizophrenia who struggle with smoking cessation. ^{1 2 5 7 8}

Research Team

Heather B Ward, MD

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

This trial is for individuals who use nicotine and have schizophrenia, as well as those without a psychotic disorder. Participants should be interested in how brain stimulation might help with nicotine cravings.

Inclusion Criteria

Age between 18-65 years

Diagnosis of either schizophrenia or schizoaffective disorder according to Diagnostic and Statistical Manual for Mental Disorders (DSM-5) criteria and confirmed by Structured Clinical Interview for the DSM (SCID) (First et al. 2015)

Current nicotine use (confirmed by expired carbon monoxide or urine cotinine)

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive rTMS treatment targeting either the DMN or L DLPFC for five consecutive days, followed by a washout period and crossover to the other treatment.

5 weeks

5 visits (in-person) per treatment phase

Follow-up

Participants are monitored for changes in functional connectivity and craving after treatment

4 weeks

Treatment Details

Interventions

• Network-Targeted Neuromodulation (Behavioural Intervention)

Trial Overview The study tests two types of transcranial magnetic stimulation (rTMS) to see if they can alter brain activity related to nicotine use and reduce cravings. It compares the effects on people with and without psychosis.

Participant Groups

Group I: L DLPFC-Targeted iTBS, Then DMN-Targeted cTBS Active Control 1 Intervention

Participants will first receive intermittent theta burst stimulation (iTBS) at 100% active motor threshold (AMT) anatomically targeted to the left dorsolateral prefrontal cortex for five consecutive days. iTBS will be administered in a pattern consisting of 2s trains of 3 pulses at 50Hz, repeated at 5Hz, every 10s for a total of 600 pulses. There will then be a washout period of at least two weeks before starting the DMN-Targeted cTBS. Participants will then receive continuous theta burst stimulation (cTBS) at 100% AMT targeted to an individual-specific map of the left parietal node of the default mode network for five consecutive days. cTBS will be administered in a pattern consisting of 1 60s train of 3 pulses at 50Hz, repeated at 5Hz, for a total of 600 pulses.

Group II: DMN-Targeted cTBS, Then L DLPFC-Targeted iTBS Active Control 1 Intervention

Participants will first receive continuous theta burst stimulation (cTBS) at 100% AMT targeted to an individual-specific map of the left parietal node of the default mode network for five consecutive days. cTBS will be administered in a pattern consisting of 1 60s train of 3 pulses at 50Hz, repeated at 5Hz, for a total of 600 pulses. There will then be a washout period of at least two weeks before starting the L DLPFC-Targeted iTBS. Participants will receive intermittent theta burst stimulation (iTBS) at 100% active motor threshold (AMT) anatomically targeted to the left dorsolateral prefrontal cortex for five consecutive days. iTBS will be administered in a pattern consisting of 2s trains of 3 pulses at 50Hz, repeated at 5Hz, every 10s for a total of 600 pulses.

Network-Targeted Neuromodulation is already approved in Canada for the following indications:

Approved in Canada as Transcranial Magnetic Stimulation for:

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

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Jeffrey R. Balser

Vanderbilt University Medical Center

Chief Executive Officer since 2009

MD and PhD from Vanderbilt University

Rick W. Wright

Vanderbilt University Medical Center

Chief Medical Officer since 2023

MD from University of Missouri-Columbia

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]

Individuals with schizophrenia have a significantly higher prevalence of tobacco use disorder, with up to 80% smoking regularly, highlighting the need for tailored treatment approaches.

Current noninvasive brain stimulation (NIBS) methods, while effective in neurotypical smokers, have shown mixed results in treating nicotine dependence in schizophrenia, suggesting that nicotine may have unique effects in this population that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive Brain Stimulation for Nicotine Dependence in Schizophrenia: A Mini Review. Ward, HB., Brady, RO., Halko, MA., et al.[2022]

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]

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]

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. Switzerland pubmed.ncbi.nlm.nih.gov

Noninvasive Brain Stimulation for Nicotine Dependence in Schizophrenia: A Mini Review. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

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

5. Italy pubmed.ncbi.nlm.nih.gov

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

6. 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]

7. England pubmed.ncbi.nlm.nih.gov

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

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

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