Accelerated Transcranial Magnetic Stimulation for Schizophrenia

Overseen By Deepak Sarpal

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Deepak K. Sarpal, M.D.

Must be taking: Clozapine

Must not be taking: Bupropion

Disqualifiers: Neurologic condition, Suicidal risk, Pregnancy, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 month

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new method to improve brain function in individuals with schizophrenia who are already taking clozapine. Researchers aim to determine if a technique using magnets, known as accelerated transcranial magnetic stimulation (specifically, accelerated intermittent theta burst stimulation or iTBS), can enhance thinking skills more effectively than a placebo treatment. Participants will undergo both real and placebo magnet sessions without knowing which is which. Individuals with schizophrenia or schizoaffective disorder who have been on clozapine for at least four months may qualify for this study. As an unphased trial, this study allows participants to contribute to innovative research that could lead to new treatment options.

Do I have to stop taking my current medications for the trial?

The trial requires participants to continue their current clozapine treatment. If you are taking both bupropion and clozapine, you cannot participate. Other medications, like serotonin and norepinephrine reuptake inhibitors, will be reviewed individually.

What prior data suggests that this accelerated transcranial magnetic stimulation is safe for neurocognition in individuals with schizophrenia?

Research shows that a treatment called accelerated transcranial magnetic stimulation, or iTBS, is generally safe for people with schizophrenia. Studies have found that iTBS can improve symptoms without major side effects. One study specifically examined safety and found that iTBS was well-tolerated, with no serious side effects compared to traditional treatments.

Although this treatment method isn't new, the faster version remains under study. Its presence in a trial indicates confidence in its safety. Participants in earlier studies did not experience severe problems, which is encouraging for those considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Accelerated Transcranial Magnetic Stimulation (aTMS) for schizophrenia because it offers a non-invasive approach that could potentially work faster than existing treatments, like antipsychotic medications. Unlike typical treatments that involve medication and can take weeks to show results, aTMS uses magnetic fields to stimulate specific areas of the brain, which might lead to quicker symptom relief. The technique is particularly promising because it doesn't involve drugs, potentially reducing side effects associated with long-term medication use. Additionally, the trial includes a unique setup where participants receive both real and sham stimulation, helping to ensure the technique's effectiveness is accurately measured.

What evidence suggests that accelerated transcranial magnetic stimulation is effective for schizophrenia?

Research shows that accelerated intermittent theta burst stimulation (iTBS) can improve social skills and reduce difficult symptoms in people with schizophrenia. Past studies have found iTBS effective for symptoms often resistant to other treatments. One study found that a personalized approach with iTBS was particularly helpful for these challenging symptoms. Additionally, iTBS proved both effective and safe compared to traditional repetitive transcranial magnetic stimulation (rTMS). In this trial, participants will receive either iTBS followed by a sham treatment or a sham treatment followed by iTBS. These encouraging results suggest that iTBS might enhance brain function, especially when combined with clozapine, a common medication for schizophrenia. ^{1 2 3 4 6}

Who Is on the Research Team?

Deepak K Sarpal, M.D.

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for individuals aged 18-50 with schizophrenia or schizoaffective disorder, who have tried at least two antipsychotic treatments without success and are on a stable dose of clozapine. It's not suitable for those with cognitive impairments, recent pregnancy, MRI contraindications like pacemakers, previous negative reactions to TMS, serious brain-affecting conditions, high suicide risk, severe substance use disorders or seizures.

Inclusion Criteria

I have been diagnosed with schizophrenia or schizoaffective disorder.

I have been treated with clozapine for at least 4 months.

I am able to understand and willing to sign the consent form.

Exclusion Criteria

Cognitive or language limitations, or any other factor that would preclude subjects providing informed consent

Contraindications for magnetic resonance imaging (e.g., a pacemaker)

I am currently taking bupropion and clozapine.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Evaluation

Participants undergo baseline evaluation and magnetic resonance imaging (MRI)

1 week

1 visit (in-person)

Treatment

Participants receive sessions of iTBS + MRI and sham delivery + MRI in a randomized order

1 month

Multiple sessions (in-person)

Follow-up

Participants are monitored for changes in brain functional connectivity and working memory network activation

1 month

What Are the Treatments Tested in This Trial?

Interventions

• Accelerated Transcranial Magnetic Stimulation

Trial Overview The study tests if accelerated intermittent theta burst stimulation (iTBS), a type of transcranial magnetic stimulation (TMS), can improve thinking abilities in people taking clozapine. Participants will receive iTBS and sham (fake) treatment in random order while blinded to the type they're getting; both sessions include an MRI scan.

How Is the Trial Designed?

Group I: iTBS, then Sham Experimental Treatment 2 Interventions

Group II: Sham, then iTBS Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

Deepak K. Sarpal, M.D.

Lead Sponsor

Trials

2

Recruited

140+

Deepak Sarpal

Lead Sponsor

Trials

1

Recruited

30+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

In an open study involving four subjects with schizophrenia, high-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex led to significant reductions in negative symptoms and improvements in function after 20 sessions over 4 weeks.

The benefits observed from rTMS were maintained one month after treatment, suggesting that this intervention is feasible, safe, and potentially beneficial for treating the deficit syndrome of schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation for the deficit syndrome of schizophrenia: a pilot investigation. Sachdev, P., Loo, C., Mitchell, P., et al.[2006]

In a multicenter trial involving 175 patients with schizophrenia, 10-Hz rTMS applied to the left dorsolateral prefrontal cortex did not show a significant improvement in negative symptoms compared to sham treatment, indicating it may not be an effective option for this specific symptom cluster.

While rTMS was well tolerated, there was a small but statistically significant improvement in positive symptoms at day 21, suggesting that while it may not help with negative symptoms, it could have some effect on other aspects of schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left prefrontal high-frequency repetitive transcranial magnetic stimulation for the treatment of schizophrenia with predominant negative symptoms: a sham-controlled, randomized multicenter trial. Wobrock, T., Guse, B., Cordes, J., et al.[2015]

Repetitive transcranial magnetic stimulation (rTMS) is a promising noninvasive treatment for schizophrenia that is safe, effective, and economical, providing an alternative to traditional antipsychotic medications.

Current antipsychotic drugs often fail to address negative symptoms and cognitive dysfunction in schizophrenia, highlighting the potential of rTMS as a complementary therapy to improve overall patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update Research Advances in the Application of Transcranial Magnetic Stimulation in the Treatment of Schizophrenia. Wu, Y., Yang, Z., Cui, S.[2022]

Repetitive transcranial magnetic stimulation (rTMS) combined with antipsychotic treatment has been shown to slightly improve negative symptoms in schizophrenia patients, based on a meta-analysis of 29 studies involving 1440 participants.

While rTMS treatment is generally well-accepted and has fewer adverse effects, it is associated with a higher rate of mild side effects, indicating the need for careful consideration in its application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy Towards Negative Symptoms and Safety of Repetitive Transcranial Magnetic Stimulation Treatment for Patients with Schizophrenia: A Systematic Review. Wang, J., Zhou, Y., Gan, H., et al.[2020]

Transcranial magnetic stimulation (TMS) has shown promise in treating persistent auditory hallucinations in schizophrenia, particularly with 1-Hz TMS applied to the left temporoparietal cortex, indicating its potential as a short-term therapeutic option.

High-frequency TMS targeting the left prefrontal cortex may help improve negative and cognitive symptoms of schizophrenia, although the effects are inconsistent and generally small, highlighting the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigational and Therapeutic Applications of Transcranial Magnetic Stimulation in Schizophrenia. Mehta, UM., Naik, SS., Thanki, MV., et al.[2022]

Bimodal repetitive transcranial magnetic stimulation (rTMS) significantly reduced symptoms of schizophrenia in 10 patients who were unresponsive to medication, with improvements noted in all subscales of the Positive and Negative Syndrome Scale (PANSS) by Day 29.

The treatment also showed potential benefits for short-term auditory verbal memory, as indicated by significant increases in neurocognitive test scores after the rTMS sessions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive treatment of bimodal repetitive transcranial magnetic stimulation (rTMS) in pharmacologically non-responsive patients with schizophrenia: a preliminary study. Oh, SY., Kim, YK.[2011]

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]

In a study involving 51 schizophrenic subjects, 20 sessions of high-frequency (10 Hz) repetitive transcranial magnetic stimulation (rTMS) significantly reduced negative symptoms of schizophrenia compared to placebo and low-frequency (1 Hz) treatments.

The results suggest that rTMS could be a promising noninvasive add-on treatment for managing negative symptoms in schizophrenia, although secondary cognitive measures did not show significant improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation (rTMS) as an augmentation treatment for the negative symptoms of schizophrenia: a 4-week randomized placebo controlled study. Schneider, AL., Schneider, TL., Stark, H.[2022]

Rhythmic transcranial magnetic stimulation (rTMS) showed significant efficacy in reducing symptoms of resistant schizophrenia, particularly in patients with depressive, hallucinatory, and negative symptoms, with reductions in PANSS scores of 24.4%, 8.3%, and 11.7% respectively after 15 sessions over 3 weeks.

However, rTMS was not effective for patients with delusional symptoms, leading to a worsening of their condition, indicating that treatment must be tailored to the specific symptoms of schizophrenia for optimal results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Augmentation therapy of resistant schizophrenia with rhythmic transcranial magnetic stimulation]. Pomytkin, AN., Tikhonov, DV., Kaleda, VG.[2023]

In a case study of a 42-year-old patient with schizophrenia, high-frequency repetitive transcranial magnetic stimulation (rTMS) significantly reduced negative and depressive symptoms compared to sham treatment over a 6-week period.

The results suggest that rTMS targeting the left dorsolateral prefrontal cortex may serve as a beneficial addition to traditional antipsychotic medications for managing negative symptoms in schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influencing negative symptoms of schizophrenia with repetitive transcranial magnetic stimulation: a case study. Prikryl, R., Skotakova, S., Kasparek, T., et al.[2016]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36603383/

Effectiveness of accelerated intermittent theta burst ... Conclusions: Accelerated iTBS can effectively ameliorate the social cognition and negative symptoms of individuals with schizophrenia. These results suggest ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X25000671

Accelerated iTBS with a personalised targeting method to ... This study is the first to investigate the efficacy of accelerated iTBS with personalised targeting method for treating negative symptoms in schizophrenia. Our ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12468741/

Accelerated Optimized Protocol of Intermittent Theta-Burst ... Introduction: Intermittent theta burst stimulation (iTBS) has been associated with improvements in the negative symptoms (NSs) of schizophrenia.

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Efficacy and safety of intermittent theta burst stimulation ... Efficacy and safety of intermittent theta burst stimulation versus repetitive transcranial magnetic stimulation for patients with schizophrenia: ...

5. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2825296

Theta Burst Stimulation Protocols for Schizophrenia Schizophrenia, a severe mental illness affecting approximately 1% of the population, is characterized by positive, negative, cognitive, and ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0022395622003430

A transdiagnostic review of safety, efficacy, and parameter ... ... transcranial magnetic stimulation in schizophrenia patients with auditory verbal hallucinations: a randomized controlled trial. PLoS One, 9 (10) (2014) ...