TMS for Schizophrenia

Overseen By Dawn Detamore

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: The University of Texas Health Science Center, Houston

Must be taking: Antipsychotics

Must not be taking: Cephalosporins, Antiarrhythmics

Disqualifiers: Epilepsy, Substance abuse, Brain conditions, others

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

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

Compensation: Varies

Number of Visits: 20

Duration: 4 weeks

140 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 mentions that participants should not be taking more than 400 mg of clozapine per day without anti-seizure medication. It's best to discuss your current medications with the trial staff.

What data supports the effectiveness of the treatment for schizophrenia?

Research suggests that transcranial magnetic stimulation (TMS), including theta burst stimulation (TBS), can help improve symptoms in schizophrenia, such as auditory hallucinations and negative symptoms. Studies have shown that TBS is well-tolerated and can be effective in reducing symptoms when used alongside medication. ^{1 2 3 4 5}

Is transcranial magnetic stimulation (TMS) safe for humans?

Research shows that transcranial magnetic stimulation (TMS), including theta burst stimulation (TBS), is generally well-tolerated and safe for humans, with few adverse effects reported. ^{1 5 6 7 8}

How is TMS treatment different from other treatments for schizophrenia?

TMS (Transcranial Magnetic Stimulation) is unique because it uses magnetic fields to stimulate specific areas of the brain, offering a non-invasive option for treating schizophrenia symptoms. Unlike traditional medications, TMS can target negative symptoms and cognitive deficits with fewer side effects, and deep-TMS can reach deeper brain areas for potentially greater effectiveness. ^{1 2 5 9 10}

What is the purpose of this trial?

The purpose of the study is to test the hypothesis that functionally navigated repetitive TMS stimulations to the prefrontal cortex (PFC) modulate aberrant cortical electrical activities at PFC circuitry. The TMS location of the PFC site will be individually localized by the symptom-related functional connectivity between PFC and symptom related areas (such as the auditory and language processing cortex). The investigators predict that such modulation will correct abnormal activities in patients with schizophrenia, reduce symptoms, especially auditory hallucination, and improve working memory/sustained attention performance.

Research Team

Xiaoming Du, PhD

Principal Investigator

The University of Texas Health Science Center, Houston

Eligibility Criteria

This trial is for adults aged 21-62 with schizophrenia, stable on their current medication for at least 4 weeks. They must be able to consent and not have a history of seizures, family epilepsy, significant substance abuse recently (except nicotine or marijuana), or take high doses of clozapine. Pregnant women and those with metal implants near the head can't participate.

Inclusion Criteria

Medication stability for 4 weeks (same drugs at same dosages)

I am 21 or older and can sign a consent form.

I am between 21 and 62 years old.

Exclusion Criteria

I have a history of seizures.

Significant alcohol or other drug use (substance dependence within 6 months or substance abuse within 1 month) other than nicotine or marijuana dependence

I do not have a pacemaker, metal implants near my head, or unstable heart disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive functionally navigated repetitive TMS stimulations to the prefrontal cortex to modulate aberrant cortical electrical activities

4 weeks

20 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Active rTMS stimulation
• Sham rTMS stimulation

Trial Overview The study tests if targeted repetitive TMS (a non-invasive brain stimulation) to the prefrontal cortex can improve symptoms like auditory hallucinations and attention in schizophrenia patients. It compares active rTMS against sham (fake) treatment to see if it corrects abnormal brain activity.

Participant Groups

Group I: Active rTMS stimulation Active Control 1 Intervention

Real active rTMS stimulation.

Group II: Sham rTMS stimulation Placebo Group 1 Intervention

Sham repetitive TMS stimulation.

Active rTMS stimulation is already approved in United States, European Union for the following indications:

Approved in United States as rTMS for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder
• Smoking Cessation

Approved in European Union as rTMS for:

• Major Depressive Disorder

Approved in United States as dTMS for:

• Treatment-Resistant Major Depressive Disorder

Approved in European Union as dTMS for:

• Treatment-Resistant Major Depressive Disorder

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Findings from Research

Theta burst stimulation (TBS) is a promising therapeutic approach for schizophrenia, showing potential benefits in treating specific symptoms and improving patient insight, based on a review of 30 studies that utilized various neuroimaging techniques.

TBS is well-tolerated and has few adverse effects, making it a feasible option for augmenting traditional pharmacotherapy in patients with schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of theta burst stimulation in patients with schizophrenia - A systematic review. Poorganji, M., Goeke, K., Zomorrodi, R., et al.[2023]

This clinical trial will compare the effects of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) and intermittent theta burst stimulation (iTBS) on negative symptoms of schizophrenia in 90 patients, aiming to provide a new treatment option for this challenging condition.

The study will also explore the impact of these treatments on depressive symptoms, cognitive performance, and smoking behavior, while using MRI and EEG to identify potential neural markers for treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and study design of a trial to assess rTMS add-on value for the amelioration of negative symptoms of schizophrenia (RADOVAN). Hebel, T., Langguth, B., Schecklmann, M., et al.[2022]

This study is a randomized, sham-controlled, double-blind trial involving 86 patients with schizophrenia spectrum disorder, testing the efficacy of continuous theta burst stimulation (cTBS) on reducing auditory verbal hallucinations (AH).

The primary goal is to measure the reduction in AH symptoms using the PSYRATS-AH score after treatment, with follow-up assessments at 1, 3, and 6 months, which will help determine the effectiveness of cTBS compared to sham treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of auditory hallucinations with bilateral theta burst stimulation (cTBS): protocol of a randomized, double-blind, placebo-controlled, multicenter trial. Plewnia, C., Brendel, B., Schwippel, T., et al.[2018]

Repetitive transcranial magnetic stimulation (rTMS) targeting the right inferior parietal lobe (IPL) significantly improved gesture performance and manual dexterity in patients with schizophrenia, indicating a potential therapeutic approach for social interaction deficits.

The study involved 20 schizophrenia patients and 20 healthy controls, and the results suggest that inhibiting interhemispheric rivalry through cTBS may enhance motor functions related to social gestures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single Session Transcranial Magnetic Stimulation Ameliorates Hand Gesture Deficits in Schizophrenia. Walther, S., Kunz, M., Müller, M., et al.[2021]

In a double-blind, placebo-controlled trial involving 71 patients with refractory auditory verbal hallucinations (AVH), both the TB-rTMS and placebo groups showed significant improvement in AVH severity, indicating that symptom reduction can occur even without specific treatment effects.

Despite the initial promise of TB-rTMS for treating AVH, the study found no significant difference in outcomes between the TB-rTMS and placebo groups, suggesting that the observed improvements may be attributed to placebo effects rather than the treatment itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Theta Burst Transcranial Magnetic Stimulation for Auditory Verbal Hallucinations: Negative Findings From a Double-Blind-Randomized Trial. Koops, S., van Dellen, E., Schutte, MJ., et al.[2022]

In a single-blind, randomized controlled study, continuous theta burst stimulation (TBS) was found to be as effective as 1 Hz repetitive transcranial magnetic stimulation (rTMS) for treating auditory verbal hallucinations in patients with schizophrenia or schizoaffective disorder.

Both therapies were administered over a 10-day treatment period, indicating that TBS may offer a comparable alternative to traditional rTMS with potentially longer-lasting effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Theta burst transcranial magnetic stimulation for the treatment of auditory verbal hallucinations: results of a randomized controlled study. Kindler, J., Homan, P., Flury, R., et al.[2022]

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]

Intermittent theta-burst stimulation, when used alongside antipsychotic medications, significantly improves negative symptoms and general psychopathology in patients with schizophrenia, based on a meta-analysis of 13 trials involving 524 patients.

The treatment is well tolerated and safe, with optimal results observed when stimulation is applied to the left dorsolateral prefrontal cortex using at least 1800 pulses per day over a minimum of 20 sessions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of intermittent theta-burst stimulation in patients with schizophrenia: A meta-analysis of randomized sham-controlled trials. Goh, KK., Chen, CH., Wu, TH., et al.[2022]

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 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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

The use of theta burst stimulation in patients with schizophrenia - A systematic review. [2023]

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

Rationale and study design of a trial to assess rTMS add-on value for the amelioration of negative symptoms of schizophrenia (RADOVAN). [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Treatment of auditory hallucinations with bilateral theta burst stimulation (cTBS): protocol of a randomized, double-blind, placebo-controlled, multicenter trial. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Single Session Transcranial Magnetic Stimulation Ameliorates Hand Gesture Deficits in Schizophrenia. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Theta Burst Transcranial Magnetic Stimulation for Auditory Verbal Hallucinations: Negative Findings From a Double-Blind-Randomized Trial. [2022]

6. Ireland pubmed.ncbi.nlm.nih.gov

Theta burst transcranial magnetic stimulation for the treatment of auditory verbal hallucinations: results of a randomized controlled study. [2022]

7. 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]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of intermittent theta-burst stimulation in patients with schizophrenia: A meta-analysis of randomized sham-controlled trials. [2022]

9. 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]

10. England pubmed.ncbi.nlm.nih.gov

Deep transcranial magnetic stimulation add-on for treatment of negative symptoms and cognitive deficits of schizophrenia: a feasibility study. [2016]