Neuromodulation for Schizophrenia

Overseen By Bhim M Adhikari

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: The University of Texas Health Science Center, Houston

Must not be taking: Clozapine

Disqualifiers: Seizures, Stroke, Substance abuse, others

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

Compensation: Varies

Number of Visits: 12

Duration: 2 weeks

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to help people with schizophrenia by using repetitive transcranial magnetic stimulation (rTMS) alongside cognitive training to improve brain function. rTMS uses magnetic pulses to stimulate parts of the brain, potentially enhancing memory and thinking skills. Individuals diagnosed with schizophrenia who can provide written consent may be suitable candidates for this study. As an unphased trial, it offers participants the chance to contribute to innovative research that could lead to new treatment options.

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 does mention that if you are taking more than 400 mg of clozapine per day without anti-seizure medication, you may be excluded. It's best to discuss your specific medications with the trial coordinators.

What prior data suggests that this neuromodulation technique is safe for patients with schizophrenia spectrum disorder?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) is safe and well-tolerated for people with schizophrenia. Studies indicate that individuals with schizophrenia do not face a higher risk of side effects like seizures when receiving rTMS. One study supported this, suggesting that rTMS is generally safe and well-tolerated for treating certain sensory issues.

Cognitive training is also safe for people with schizophrenia. Research has found that computer-based cognitive training can enhance mental well-being and cognitive skills without major safety concerns.

Overall, both rTMS and cognitive training have strong safety records, making them promising options for those considering participation in related clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using active repetitive transcranial magnetic stimulation (rTMS) for schizophrenia because it offers a non-invasive approach that directly targets brain activity. Unlike traditional medications that often focus on chemical imbalances, rTMS uses magnetic fields to modulate neural circuits, potentially reducing symptoms with fewer side effects. Additionally, when combined with cognitive training, rTMS may enhance cognitive function and provide quicker, more comprehensive improvements compared to standard treatments.

What evidence suggests that active rTMS combined with cognitive training is effective for schizophrenia?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) can reduce symptoms of schizophrenia. Studies indicate that rTMS effectively decreases auditory hallucinations and improves symptoms such as lack of motivation and social difficulties. It also aids in planning and memory, which are crucial for daily activities.

In this trial, participants will receive a combination of rTMS and cognitive training. Cognitive training improves thinking skills, and reviews have shown it can enhance memory and cognition, with some benefits for daily life. Combining rTMS with cognitive training might offer a better chance of improving symptoms for people with schizophrenia. ^{3 4 6 7 8}

Who Is on the Research Team?

Xiaoming Du, PhD

Principal Investigator

The University of Texas Health Science Center, Houston

Are You a Good Fit for This Trial?

This trial is for men and women aged 18-60 with schizophrenia-spectrum disorder who can consent to participate. Excluded are those with a history of seizures, major medical issues affecting brain function, high clozapine doses without anti-seizure meds, substance abuse, thrombosis risks, pregnancy without contraception use, significant head injury or brain surgery, and inability to abstain from alcohol/marijuana before experiments.

Inclusion Criteria

I have been diagnosed with a schizophrenia-spectrum disorder.

Evaluation to Sign Consent (ESC) above 10

Exclusion Criteria

I am pregnant or able to become pregnant and not using birth control.

I take more than 400 mg of clozapine daily and am not on any anti-seizure medication.

I am unable to give my consent for treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive active repetitive transcranial magnetic stimulation (rTMS) combined with cognitive training for up to 10 treatment visits

2 weeks

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Active rTMS
• Cognitive Training

Trial Overview

The study tests if active repetitive transcranial magnetic stimulation (rTMS) using an H coil combined with cognitive training can improve white matter integrity in patients diagnosed with schizophrenia spectrum disorder.

How Is the Trial Designed?

Group I: Active rTMS combined with Cognitive Training Experimental Treatment 2 Interventions

Participants will receive active H-coil delivered rTMS, as well as cognitive training in each treatment visit for up to 10 treatment visits within about 2 weeks. In each visit, there are three rTMS sessions and each of them is followed by a cognitive training session and a rest period, which allows the inter-rTMS-session interval to be about 30 minutes.

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

Published Research Related to This Trial

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]

In a study involving 32 chronic schizophrenia in-patients, high-frequency rTMS (10 Hz) applied over two weeks did not lead to any significant deterioration in cognitive performance, indicating good tolerability of the treatment.

Patients with poorer baseline performance on cognitive tests showed improvement in psychopathology after rTMS treatment, suggesting potential benefits for cognitive function in certain individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The tolerability of rTMS treatment in schizophrenia with respect to cognitive function. Mittrach, M., Thünker, J., Winterer, G., et al.[2010]

In a study involving 16 patients with schizophrenia, high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) over the left dorsolateral prefrontal cortex did not show significant effects on negative symptoms compared to sham treatment.

While there was a trend for improvement in some symptoms with sham rTMS, the study concluded that HF-rTMS is not effective for treating negative symptoms of schizophrenia, suggesting the need for exploring alternative rTMS methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The double-blind sham-controlled study of high-frequency rTMS (20 Hz) for negative symptoms in schizophrenia: negative results. Novák, T., Horácek, J., Mohr, P., et al.[2006]

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]

In a re-analysis of the RESIS trial data, repetitive transcranial magnetic stimulation (rTMS) applied to the left dorsolateral prefrontal cortex showed a significant improvement in the PANSS excitement factor immediately after treatment compared to the sham group, although this effect did not last in follow-up assessments.

Overall, the study found no significant long-term benefits of active rTMS over sham treatment for negative symptoms in schizophrenia, suggesting that while there may be short-term improvements, rTMS may not provide a sustained therapeutic advantage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of high-frequency repetitive transcranial magnetic stimulation on PANSS factors in schizophrenia with predominant negative symptoms - Results from an exploratory re-analysis. Hansbauer, M., Wobrock, T., Kunze, B., et al.[2018]

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 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]

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]

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]

Citations

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

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In the intention-to-treat analyses, patients receiving active rTMS showed a significantly greater reduction in AHRS scores compared with those ...

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Most reviews indicate that rTMS has an effect on negative symptoms, executive function, working memory, and language function in patients with schizophrenia.

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The primary outcome is improvement in negative symptoms related to schizophrenia. The investigators are focusing on negative symptoms given their greater ...

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Of the randomized, controlled studies, 10 studies involving a total of 257 subjects with psychosis revealed positive results in treating auditory hallucinations ...

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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.

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pmc.ncbi.nlm.nih.gov/articles/PMC3656498/

Safety and tolerability of repetitive transcranial magnetic ...

The published data suggest rTMS for the treatment or diagnosis of pathologic positive sensory phenomena appears to be a relatively safe and well-tolerated ...

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Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Negative Symptoms in Schizophrenia (RESIS) · Study Overview · Contacts and Locations.