TMS for Schizophrenia

(MESSI Trial)

Overseen By Miriam Mathew, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Francisco

Must be taking: Antipsychotics

Disqualifiers: Neurological disorder, Seizures, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 week

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how navigated repetitive transcranial magnetic stimulation (nrTMS) can address self-agency issues in individuals with schizophrenia. Self-agency refers to the feeling of control over one's actions. The trial aims to determine if nrTMS can improve cognitive skills, symptoms, and daily life by targeting a specific brain area. Individuals diagnosed with schizophrenia who have been stable on their medication for some time may be suitable candidates. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could enhance treatment options for schizophrenia.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires schizophrenia participants to be on a stable dose of antipsychotic medication for at least 4 weeks. It seems you can continue your current medications if they meet this stability requirement.

What prior data suggests that navigated repetitive transcranial magnetic stimulation (nrTMS) is safe for schizophrenia patients?

Research has shown that navigated repetitive transcranial magnetic stimulation (nrTMS) is safe for people with schizophrenia. Studies have found that nrTMS does not cause serious side effects such as weight gain, involuntary movements, or diabetes. Most individuals tolerate it well, and it does not increase the risk of seizures. This treatment uses magnetic fields to target specific brain areas and has safely helped alleviate schizophrenia symptoms. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using Navigated Repetitive Transcranial Magnetic Stimulation (nrTMS) for schizophrenia because it offers a non-invasive way to target specific brain areas linked to the condition. Unlike standard treatments like antipsychotic medications, which can have numerous side effects and work by altering neurotransmitter levels, nrTMS uses magnetic fields to stimulate nerve cells in the brain directly. The technique specifically targets the medial/superior prefrontal cortex, which is believed to play a crucial role in managing symptoms of schizophrenia. This targeted approach could potentially provide relief with fewer side effects and faster results compared to traditional methods.

What evidence suggests that navigated repetitive transcranial magnetic stimulation (nrTMS) is effective for schizophrenia?

Research has shown that navigated repetitive transcranial magnetic stimulation (nrTMS) can alleviate some symptoms of schizophrenia. In this trial, participants will receive nrTMS targeting different brain areas. The Medial/Superior Prefrontal TMS arm applies 10 Hz high-frequency TMS to the mPFC, while the Posterior Parietal TMS arm serves as a placebo comparator. Studies have found that nrTMS might reduce auditory hallucinations and improve memory in some individuals with schizophrenia. This treatment uses magnetic pulses to target specific brain regions, potentially altering brain activity and enhancing mental function. Additionally, nrTMS has been associated with better self-control and overall symptom relief when combined with regular medication. These findings suggest that nrTMS could enhance cognitive function and daily life for people with schizophrenia. ^{1 2 4 6 7}

Who Is on the Research Team?

Karuna Subramaniam, PhD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for English-speaking individuals with schizophrenia who are clinically stable on a low to moderate dose of antipsychotic medication, without neurological disorders or substance use issues. They must be in good physical health and able to undergo MRI scans. Pregnant individuals, those with implanted metal/electronic devices, scalp wounds/infections, ongoing seizures, or severe claustrophobia cannot participate.

Inclusion Criteria

You have undergone an MRI scan and the results meet the requirements for the study.

You are not currently struggling with addiction to alcohol or drugs.

I am in good overall health.

Exclusion Criteria

I have wounds or infections on my scalp.

You are afraid of being in small spaces and cannot undergo an MRI.

You have metal implants or electronic devices inside your body.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Baseline Assessment

Participants complete baseline assessments including cognitive, clinical, and daily functioning assessments, structural MRI, and MEGI scans

1 week

Multiple visits (in-person)

Treatment

Participants receive nrTMS targeting either the medial prefrontal cortex or a control posterior parietal site

1 week

Multiple visits (in-person)

Follow-up

Participants are monitored for changes in neural activity, cognition, clinical symptoms, and daily functioning after TMS

4 weeks

Multiple visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Navigated Repetitive Transcranial Magnetic Stimulation (nrTMS)

Trial Overview The study tests whether high-frequency transcranial magnetic stimulation (TMS) targeting the medial prefrontal cortex can improve self-agency judgments in people with schizophrenia. It will also assess cognitive improvements and daily functioning as well as potential changes within the brain's self-agency network.

How Is the Trial Designed?

Group I: Medial/Superior Prefrontal TMS Active Control 1 Intervention

10 Hz High frequency TMS applied to the mPFC

Group II: Posterior Parietal TMS Placebo Group 1 Intervention

10 Hz high frequency TMS applied to the posterior parietal cortex

Navigated Repetitive Transcranial Magnetic Stimulation (nrTMS) is already approved in European Union, United States for the following indications:

Approved in European Union as rTMS for:

• Major Depressive Disorder
• Negative symptoms in schizophrenia

Approved in United States as rTMS for:

• Major Depressive Disorder

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

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 80 schizophrenia patients, 20 Hz rTMS significantly improved visual spatial working memory, while theta burst stimulation (TBS) notably enhanced verbal fluency, indicating that different rTMS paradigms can target specific cognitive deficits.

Both TBS and 10 Hz rTMS effectively alleviated negative symptoms of schizophrenia, while general psychopathology symptoms improved with 10 Hz and 20 Hz rTMS, suggesting that rTMS can be tailored for individual therapeutic needs in schizophrenia treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effects of repetitive transcranial magnetic stimulation with different paradigms on the cognitive function and psychotic symptoms of schizophrenia patients]. Zheng, LN., Guo, Q., Li, H., et al.[2017]

In a study involving 10 right-handed schizophrenia patients, active repetitive transcranial magnetic stimulation (rTMS) at 10 Hz significantly improved negative symptoms of schizophrenia compared to sham treatment.

The improvement in negative symptoms occurred independently of any changes in depressive symptoms, suggesting that rTMS specifically targets negative symptoms in schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of adjuvant high frequency repetitive transcranial magnetic stimulation on negative and positive symptoms of schizophrenia: preliminary results of a double-blind sham-controlled study. Goyal, N., Nizamie, SH., Desarkar, P.[2007]

A multicenter, randomized, sham-controlled trial is being conducted to evaluate the efficacy of high-frequency rTMS as an add-on treatment for negative symptoms in schizophrenia, involving 63 patients in each group over a 3-week period with follow-up for 12 weeks.

The primary goal is to assess the reduction of negative symptoms using the PANSS score, while also examining other factors like neurocognition and quality of life to understand the mechanisms of rTMS, although challenges such as antipsychotic dosage changes may affect results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation for the treatment of negative symptoms in residual schizophrenia: rationale and design of a sham-controlled, randomized multicenter study. Cordes, J., Falkai, P., Guse, B., et al.[2021]

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]

In a study of 47 patients with schizophrenia, active rTMS over the left dorsolateral prefrontal cortex showed no immediate effect on negative symptoms at 4 weeks, but by 8 weeks, there was a significant reduction in symptoms compared to the sham group.

These results indicate that rTMS may have a delayed therapeutic effect on negative symptoms of schizophrenia, suggesting it could be a beneficial treatment option over a longer duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delayed effect of repetitive transcranial magnetic stimulation (rTMS) on negative symptoms of schizophrenia: Findings from a randomized controlled trial. Li, Z., Yin, M., Lyu, XL., et al.[2018]

A preliminary study involving 15 patients with schizophrenia showed that 20 daily sessions of deep transcranial magnetic stimulation (deep-TMS) significantly improved cognitive deficits and negative symptoms.

The improvements in symptoms were sustained for at least two weeks after the treatment, suggesting that deep-TMS could be a promising add-on therapy for managing these challenging aspects of schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep transcranial magnetic stimulation add-on for treatment of negative symptoms and cognitive deficits of schizophrenia: a feasibility study. Levkovitz, Y., Rabany, L., Harel, EV., et al.[2016]

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]

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]

Transcranial magnetic stimulation (TMS) is generally considered a safe treatment option for managing symptoms of schizophrenia, particularly in reducing auditory hallucinations, based on a review of 19 studies involving 531 patients.

There are ongoing controversies regarding the effects of TMS on the cortical silent period in schizophrenia patients, with some studies showing longer or shorter periods compared to healthy controls, indicating potential GABA receptor abnormalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Different Modalities of Transcranial Magnetic Stimulation to Manage Schizophrenia. Soltani, E., Bateni, H., Shad, MU.[2022]

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]

Citations

1. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2825941

Repetitive Transcranial Magnetic Stimulation for Auditory ... The findings of this randomized clinical trial suggest that imaging-navigated rTMS may effectively and safely alleviate AVH in patients with schizophrenia.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4558786/

Efficacy of Transcranial Magnetic Stimulation (TMS) in the ... Of the randomized, controlled studies, 10 studies involving a total of 257 subjects with psychosis revealed positive results in treating auditory hallucinations ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10193754/

A Possible Role of BDNF Polymorphism In addition, patients with the CC homozygotes demonstrated greater improvement of immediate memory after rTMS treatment, while T allele carriers showed no ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0022395625003450

Early improvement of psychopathological symptoms with ... Early improvements were significantly related to the 8-week improvements. Add-on rTMS treatment as a supplement to antipsychotics could potentially increase the ...

5. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1496562/full

Effects of repetitive transcranial magnetic stimulation on ... In summary, this study demonstrates that rTMS targeting the DLPFC can significantly improve inhibitory control in individuals with schizophrenia ...

6. academic.oup.com academic.oup.com/schizophreniabulletin/article/51/2/392/7758322

Safety of rTMS for Schizophrenia: A Systematic Review and ... rTMS is safe and well tolerated for people with schizophrenia. Individuals with schizophrenia are not at increased risk for adverse effects, including seizure.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04853485

Study Details | NCT04853485 | Repetitive Transcranial ... Efficacy Towards Negative Symptoms and Safety of Repetitive Transcranial Magnetic Stimulation Treatment for Patients with Schizophrenia: A Systematic Review.