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

Trial Summary

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 data supports the effectiveness of the treatment Active rTMS, Cognitive Training for schizophrenia?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can improve negative symptoms in people with schizophrenia, especially when other treatments haven't worked. Studies found that high-frequency rTMS applied to specific brain areas led to significant improvements in these symptoms. ^{1 2 3 4 5}

Is repetitive transcranial magnetic stimulation (rTMS) safe for humans?

Repetitive transcranial magnetic stimulation (rTMS) is generally considered safe for humans, as studies have shown it to be a promising method for treating mental disorders like schizophrenia without significant safety concerns. ^{1 5 6 7 8}

How does the treatment rTMS differ from other treatments for schizophrenia?

Repetitive transcranial magnetic stimulation (rTMS) is a unique treatment for schizophrenia that uses magnetic fields to stimulate nerve cells in the brain, specifically targeting the left dorsolateral prefrontal cortex. Unlike traditional medications, rTMS is non-invasive and focuses on improving negative symptoms, which are often resistant to standard antipsychotic treatments. ^{2 5 8 9 10}

What is the purpose of this trial?

Patients with schizophrenia spectrum disorder (SSD) will be exposed to active repetitive transcranial magnetic stimulation (rTMS) from H coil combined with cognitive training for improving white matter integrity.

Research Team

Xiaoming Du, PhD

Principal Investigator

The University of Texas Health Science Center, Houston

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

References

1. 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]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Treatment of negative symptoms of schizophrenia using repetitive transcranial magnetic stimulation in a double-blind, randomized controlled study. [2022]

3. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Augmentation therapy of resistant schizophrenia with rhythmic transcranial magnetic stimulation]. [2023]

4. England pubmed.ncbi.nlm.nih.gov

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

5. United States 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. [2007]

6. Germany pubmed.ncbi.nlm.nih.gov

The tolerability of rTMS treatment in schizophrenia with respect to cognitive function. [2010]

7. China pubmed.ncbi.nlm.nih.gov

Efficacy Towards Negative Symptoms and Safety of Repetitive Transcranial Magnetic Stimulation Treatment for Patients with Schizophrenia: A Systematic Review. [2020]

8. United States 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. [2015]

9. Ireland 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. [2018]

10. Sweden pubmed.ncbi.nlm.nih.gov

The double-blind sham-controlled study of high-frequency rTMS (20 Hz) for negative symptoms in schizophrenia: negative results. [2006]