dTMS for Smoking Cessation in Schizophrenia
Recruiting in Palo Alto (17 mi)
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Stony Brook University
Must not be taking: Smoking cessation products, Clozapine
Disqualifiers: Substance use disorder, Epilepsy, Pregnancy, others
No Placebo Group
Approved in 2 jurisdictions
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.
12345Is 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.
12678How 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.
12469Eligibility 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
+3 more
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.
+10 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Active deep transcranial magnetic stimulation (dTMS)Experimental Treatment1 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: ShamPlacebo Group1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Stony Brook UniversityStony Brook, NY
Loading ...
Who Is Running the Clinical Trial?
Stony Brook UniversityLead Sponsor
National Institute on Drug Abuse (NIDA)Collaborator
References
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]High rates of tobacco smoking and smoking cessation failure in schizophrenia may be related to prefrontal cortical dysfunction. Novel treatment options for tobacco use disorder are needed given the limited efficacy of current pharmacotherapies. Preliminary evidence suggests high-frequency repetitive transcranial magnetic stimulation (rTMS) to bilateral dorsolateral prefrontal cortex (DLPFC) may suppress tobacco craving in smokers with schizophrenia. The goal of this study was to determine effects of rTMS for tobacco craving and cognition using a short-term (3-day) human laboratory paradigm.
Repetitive transcranial magnetic stimulation reduces cigarette consumption in schizophrenia patients. [2017]High-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) seemed to decrease tobacco consumption and craving in nicotine-dependent people without psychiatric disorder or otherwise healthy people. Even if the prevalence of cigarette smoking in schizophrenia patients is high and estimated to be between 45% and 88%, this technique has not been systematically studied in this indication in schizophrenia yet.
Investigating repetitive transcranial magnetic stimulation on cannabis use and cognition in people with schizophrenia. [2022]Cannabis use disorder (CUD) occurs at high rates in schizophrenia, which negatively impacts its clinical prognosis. These patients have greater difficulty quitting cannabis which may reflect putative deficits in the dorsolateral prefrontal cortex (DLPFC), a potential target for treatment development. We examined the effects of active versus sham high-frequency (20-Hz) repetitive transcranial magnetic stimulation (rTMS) on cannabis use in outpatients with schizophrenia and CUD. Secondary outcomes included cannabis craving/withdrawal, psychiatric symptoms, cognition and tobacco use. Twenty-four outpatients with schizophrenia and CUD were enrolled in a preliminary double-blind, sham-controlled randomized trial. Nineteen participants were randomized to receive active (n = 9) or sham (n = 10) rTMS (20-Hz) applied bilaterally to the DLPFC 5x/week for 4 weeks. Cannabis use was monitored twice weekly. A cognitive battery was administered pre- and post-treatment. rTMS was safe and well-tolerated with high treatment retention (~90%). Contrast estimates suggested greater reduction in self-reported cannabis use (measured in grams/day) in the active versus sham group (Estimate = 0.33, p = 0.21; Cohen's d = 0.72), suggesting a clinically relevant effect of rTMS. A trend toward greater reduction in craving (Estimate = 3.92, p = 0.06), and significant reductions in PANSS positive (Estimate = 2.42, p = 0.02) and total (Estimate = 5.03, p = 0.02) symptom scores were found in the active versus sham group. Active rTMS also improved attention (Estimate = 6.58, p
Preventing relapse to smoking with transcranial magnetic stimulation: Feasibility and potential efficacy. [2022]Many smokers attempt to quit every year, but 90% relapse within 12 months. Converging evidence suggests relapse is associated with insufficient activation of the prefrontal cortex. Delay discounting rate reflects relative activity in brain regions associated with relapse. High-frequency repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (LDLPFC) increases cortical excitability and reduces delay discounting rates, but little is known about feasibility, tolerability, and potential efficacy for smoking cessation. We hypothesized that 8 sessions of 20Hz rTMS of the LDLPFC combined with an evidence-based self-help intervention will demonstrate feasibility, tolerability, and potential efficacy in a limited double-blind randomized control trial. Smokers (n=29), abstinent for 24h, motivated to quit, and not using cessation medications, were randomized to active 20Hz rTMS at 110% of Motor Threshold or sham stimulation that replicated the look and sound of active stimulation. Stimulation site was located using the 6cm rule and neuro-navigation. Multiple clinical, feasibility, tolerability, and efficacy measures were examined. Active rTMS decreased delay discounting of $100 (F (1, 25.3694)=4.14, p=.05) and $1000 (F (1, 25.169)=8.42, p<.01), reduced the relative risk of relapse 3-fold (RR 0.29, CI 0.10-0.76, Likelihood ratio χ2 with 1 df=6.40, p=.01), increased abstinence rates (active 50% vs. sham 15.4%, Χ2 (df=1)=3.80, p=.05), and increased uptake of the self-help intervention. Clinical, feasibility, and tolerability assessments were favorable. Combining 20Hz rTMS of the LDLPFC with an evidence-based self-help intervention is feasible, well-tolerated, and demonstrates potential efficacy.
Repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex reduces nicotine cue craving. [2022]Repetitive transcranial magnetic stimulation (rTMS) can noninvasively stimulate the brain and transiently amplify or block behaviors mediated through a region. We hypothesized that a single high-frequency rTMS session over the left dorsolateral prefrontal cortex (DLPFC) would reduce cue craving for cigarettes compared with a sham TMS session.
Repetitive Transcranial Magnetic Stimulation for Tobacco Treatment in Cancer Patients: A Preliminary Report of a One-Week Treatment. [2022]Smoking cessation represents a significant opportunity to improve cancer survival rates, reduces the risk of cancer treatment complications, and improves quality of life. However, about half of cancer patients who smoke continue to smoke despite the availability of several treatments. Previous studies demonstrate that repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) decreases cue craving, reduces cigarette consumption, and increases the quit rate in tobacco use disorder. We investigated whether 5 sessions of rTMS can be safely and efficaciously used for smoking cessation in cancer patients.
[Effectiveness and safety of high dose transcranial magnetic stimulation in schizophrenia with refractory negative symptoms: a randomized controlled study]. [2018]To evaluate the efficacy and safety of high dose transcranial magnetic stimulation (rTMS) in patients with schizophrenia with refractory negative symptoms.
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.
Deep rTMS of the insula and prefrontal cortex in smokers with schizophrenia: Proof-of-concept study. [2022]Patients with schizophrenia have a high prevalence of cigarette smoking and respond poorly to conventional treatments, highlighting the need for new therapies. We conducted a mechanistic, proof-of-concept study using bilateral deep repetitive transcranial magnetic stimulation (dTMS) of insular and prefrontal cortices at high frequency, using the specialized H4 coil. Feasibility of dTMS was tested for disruption of tobacco self-administration, insula target engagement, and insula circuit modulation, all of which were a priori outcomes of interest. Twenty patients completed the study, consisting of weekday dTMS sessions (randomization to active dTMS or sham; double-blind; 10 patients per group), a laboratory tobacco self-administration paradigm (pre/post assessments), and multimodal imaging (three MRI total sessions). Results showed that participants assigned to active dTMS were slower to initiate smoking their first cigarette compared with sham, consistent with smoking disruption. The imaging analyses did not reveal significant Time × Group interactions, but effects were in the anticipated directions. In arterial spin labeling analyses testing for target engagement, an overall decrease in insula blood flow, measured during a post-treatment MRI versus baseline, was numerically more pronounced in the active dTMS group than sham. In fMRI analyses, resting-state connectivity between the insula and default mode network showed a numerically greater change from baseline in the active dTMS group than sham, consistent with a functional change to insula circuits. Exploratory analyses further suggested a therapeutic effect of dTMS on symptoms of psychosis. These initial observations pave the way for future confirmatory studies of dTMS in smoking patients with schizophrenia.