Neuromodulation for Schizophrenia

Overseen By Phillip Gerretson, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Scion NeuroStim

Must be taking: Antipsychotics

Disqualifiers: Cardiovascular disease, Seizures, Substance dependence, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

34 Participants Needed

Trial Summary

What is the purpose of this trial?

Our proposed study employs a novel approach to determine the clinical and functional imaging effects of brainstem neuromodulation, with an investigational study device, on illness awareness in schizophrenia - a significant contributor to medication non-adherence and poor treatment outcomes, and arguably the most treatment resistant manifestation of the disorder. The study device under investigation provides a safe and non-invasive method of brainstem stimulation that will be used in conjunction with a neuroimaging biomarker to measure brain changes associated with treatment and illness awareness.

Will I have to stop taking my current medications?

The trial requires that participants have been on a stable dose of their antipsychotic and other medications for at least 2 months before joining, and they should not expect to change doses during the study.

What data supports the effectiveness of the treatment for schizophrenia?

Research shows that non-invasive brain stimulation techniques, like repetitive transcranial magnetic stimulation (rTMS), have shown promise in treating symptoms of schizophrenia, such as negative symptoms and auditory hallucinations. However, more research is needed to fully understand their effectiveness and improve treatment outcomes. ^{1 2 3 4 5}

Is neuromodulation safe for humans?

Research on non-invasive brain stimulation, including techniques like transcutaneous vagus nerve stimulation (tVNS), shows that these methods are generally well tolerated with no significant adverse effects reported in studies involving schizophrenia patients. ^{1 2 3 6 7}

How is the non-invasive brainstem modulation device treatment for schizophrenia different from other treatments?

The non-invasive brainstem modulation device is unique because it uses non-invasive brain stimulation to potentially improve symptoms of schizophrenia by modulating neural plasticity (the brain's ability to change and adapt), which is different from traditional drug treatments that primarily target chemical imbalances in the brain. ^{2 4 8 9 10}

Eligibility Criteria

This trial is for adults over 18 with schizophrenia or schizoaffective disorder, who have trouble recognizing their illness. They must speak English, be on stable medication for two months, and able to consent. Excluded are those with recent eye surgery, ear infections, substance dependence (except caffeine/nicotine), metal implants/pacemakers affecting MRI scans, pregnancy, vestibular dysfunction, severe medical conditions or thought disorders.

Inclusion Criteria

Moderate-to-severe lack of illness awareness ≤7 on the VAGUS-SR, which corresponds to a rating of ≥3 on PANSS G12 Insight and Judgment item

I am willing and able to agree to participate in this study.

Fluent in English

Exclusion Criteria

Unwilling or unable to consent to the study

I use hearing aids or have chronic ear problems.

Metal implants or a pacemaker that would preclude the MRI scan

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive brainstem neuromodulation using an investigational study device, with neuroimaging to measure brain changes

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Non-invasive brainstem modulation device

Trial Overview The study tests a non-invasive brainstem modulation device's effect on illness awareness in schizophrenia patients. It involves safe brain stimulation alongside neuroimaging to track changes in the brain related to treatment response and recognition of the illness.

Participant Groups

Group I: Investigational Stimulation Pattern-Open Label Experimental Treatment 1 Intervention

Group II: Investigational Stimulation Pattern 2-Randomized Experimental Treatment 1 Intervention

Group III: Investigational Stimulation Pattern 1-Randomized Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Scion NeuroStim

Lead Sponsor

Trials

14

Recruited

550+

Centre for Addiction and Mental Health

Collaborator

Trials

388

Recruited

84,200+

Findings from Research

Non-invasive brain stimulation techniques, particularly repetitive transcranial magnetic stimulation (rTMS), show promise as add-on therapies for managing difficult symptoms of schizophrenia, such as negative symptoms and persistent auditory hallucinations, although some studies have reported mixed results.

Electroconvulsive therapy (ECT) remains the most established treatment, while newer methods like rTMS and transcranial direct current stimulation (tDCS) offer potential based on a better understanding of the underlying brain mechanisms, but further research is needed to confirm their clinical efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Non-invasive brain stimulation for treatment of schizophrenic psychoses]. Hasan, A., Wobrock, T., Palm, U., et al.[2018]

Recent randomized-controlled trials indicate that noninvasive brain stimulation can provide long-lasting relief from symptoms in patients with treatment-resistant schizophrenia.

Innovative stimulation techniques, such as theta burst stimulation and new electrical methods, have shown promising results, suggesting that optimizing stimulation parameters could enhance treatment efficacy for schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances in noninvasive brain stimulation for schizophrenia. Brunelin, J., Adam, O., Mondino, M.[2023]

A study involving 20 stable schizophrenia patients tested the safety and efficacy of transcutaneous vagus nerve stimulation (tVNS) over 26 weeks, finding that the treatment was well tolerated with no significant adverse effects.

However, the study did not show a statistically significant improvement in schizophrenia symptoms compared to sham stimulation, suggesting that while tVNS is safe, it may not be effective for this condition in the current trial setup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous noninvasive vagus nerve stimulation (tVNS) in the treatment of schizophrenia: a bicentric randomized controlled pilot study. Hasan, A., Wolff-Menzler, C., Pfeiffer, S., et al.[2018]

Non-invasive brain stimulation techniques show promise in modulating neural plasticity and treating schizophrenia, supported by numerous clinical trials demonstrating efficacy.

Despite the encouraging results, there is still a limited understanding of the neurobiological mechanisms behind these treatments, indicating a need for further research to enhance their effectiveness and consistency among individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulating neural plasticity with non-invasive brain stimulation in schizophrenia. Hasan, A., Wobrock, T., Rajji, T., et al.[2022]

A review of 119 studies on non-invasive brain stimulation (NIBS) for treatment-resistant schizophrenia revealed a low quality of assessment, with an average score of only 3.38 out of 11, indicating inadequate reporting of treatment resistance.

Most studies inadequately defined treatment resistance, often focusing on a single symptom without considering factors like treatment adherence and functional impairment, which limits the understanding of NIBS's true efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of treatment resistance criteria in non-invasive brain stimulation studies of schizophrenia. Kronick, J., Sabesan, P., Burhan, AM., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) has a significant effect on reducing negative symptoms in schizophrenia, with a mean effect size of 0.64 based on 22 studies involving 827 participants, indicating it is more effective than sham stimulation.

Transcranial direct current stimulation (tDCS) also shows promise, with a mean effect size of 0.50 from 5 studies with 134 participants, but the evidence is less robust compared to rTMS, suggesting that more research is needed to fully understand its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moderate effects of noninvasive brain stimulation of the frontal cortex for improving negative symptoms in schizophrenia: Meta-analysis of controlled trials. Aleman, A., Enriquez-Geppert, S., Knegtering, H., et al.[2019]

Current antipsychotics may not effectively address negative symptoms of schizophrenia, highlighting the need for targeted treatments specifically for these symptoms.

Recent studies have explored various novel treatment approaches, including glutamatergic and nicotinic-acetylcholinergic therapies, as well as behavioral interventions like physical exercise, but challenges in trial design and variability in symptom assessment complicate the evaluation of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing Negative Symptoms of Schizophrenia: How Far Have We Come? Kantrowitz, JT.[2018]

Electroconvulsive therapy (ECT) is a well-established and recommended treatment for acute psychosis symptoms, particularly effective in patients with treatment-resistant first episode psychosis, such as schizophrenia.

Other neuromodulation techniques like transcranial magnetic stimulation and vagus nerve stimulation lack sufficient evidence to support their use in treating psychosis, making ECT a more reliable option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electroconvulsive Therapy and Other Neuromodulation Techniques for the Treatment of Psychosis. Maley, CT., Becker, JE., Shultz, EKB.[2019]

Over the past 80 years, non-pharmacological biological therapies for schizophrenia, particularly convulsive therapy, have evolved significantly, highlighting their historical importance in treatment.

The review discusses the effectiveness of electroconvulsive therapy (ECT) for certain clinical conditions and introduces new neurostimulation techniques like Transcranial Magnetic Stimulation (TMS) as emerging treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-pharmacological biological therapies in schizophrenia. Gazdag, G., Ungvari, GS.[2018]

Repetitive transcranial magnetic stimulation (rTMS) targeting the dorsolateral prefrontal cortex (DLPFC) shows promise in reducing cannabis and tobacco use in individuals with schizophrenia, based on a review of seven studies.

While rTMS appears to be a safe and effective approach for managing substance use disorders in patients with psychotic disorders, the evidence for transcranial direct current stimulation (tDCS) remains inconclusive, highlighting the need for further research with larger clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuromodulation to Treat Substance Use Disorders in People With Schizophrenia and Other Psychoses: A Systematic Review. Johnstone, S., Sorkhou, M., Al-Saghir, N., et al.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

[Non-invasive brain stimulation for treatment of schizophrenic psychoses]. [2018]

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

Recent advances in noninvasive brain stimulation for schizophrenia. [2023]

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

Transcutaneous noninvasive vagus nerve stimulation (tVNS) in the treatment of schizophrenia: a bicentric randomized controlled pilot study. [2018]

4. Germany pubmed.ncbi.nlm.nih.gov

Modulating neural plasticity with non-invasive brain stimulation in schizophrenia. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Assessment of treatment resistance criteria in non-invasive brain stimulation studies of schizophrenia. [2022]

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

Moderate effects of noninvasive brain stimulation of the frontal cortex for improving negative symptoms in schizophrenia: Meta-analysis of controlled trials. [2019]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Managing Negative Symptoms of Schizophrenia: How Far Have We Come? [2018]

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

Electroconvulsive Therapy and Other Neuromodulation Techniques for the Treatment of Psychosis. [2019]

9. Hungary pubmed.ncbi.nlm.nih.gov

Non-pharmacological biological therapies in schizophrenia. [2018]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Neuromodulation to Treat Substance Use Disorders in People With Schizophrenia and Other Psychoses: A Systematic Review. [2022]