Non-invasive Neuromodulation for Schizophrenia

Overseen By Ariel Graff, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Centre for Addiction and Mental Health

Must be taking: Antipsychotics

Disqualifiers: Hearing aids, Eye surgery, Cardiovascular, Seizures, others

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new brain device designed to help people with schizophrenia better understand their illness. Participants will receive either real or sham stimulation using a non-invasive brain device (an investigational brainstem neuromodulation device) to determine if it improves their awareness of their condition. Researchers will also examine changes in brain activity to understand how the treatment works. Individuals with schizophrenia or schizoaffective disorder who struggle with understanding their illness and have a stable medication plan may be suitable for this study. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could enhance the understanding and treatment of schizophrenia.

Will I have to stop taking my current medications?

The trial requires that participants stay on a stable dose of their current antipsychotic and other medications for at least 2 months before and during the study, so you will not need to stop taking them.

What prior data suggests that this non-invasive neuromodulation device is safe for schizophrenia?

Research shows that the investigational brainstem neuromodulation device safely and non-invasively stimulates the brain. Previous studies found that patients generally tolerate this device well. These trials reported no major side effects, suggesting the treatment is safe. Participants received the treatment without major problems, making it a promising option for those considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this investigational brainstem neuromodulation device for schizophrenia because it's a non-invasive option that stands apart from the standard antipsychotic medications, which often come with a range of side effects. Most treatments for schizophrenia focus on altering neurotransmitter levels, but this device directly stimulates the brainstem, potentially offering a new way to manage symptoms. Unlike traditional medications that can take weeks to show effects, this method has the potential to provide quicker symptom relief. Plus, the ability to offer an open-label phase allows participants who initially receive a placebo to try the active treatment, enhancing the overall potential for positive outcomes.

What evidence suggests that this neuromodulation device is effective for improving illness awareness in schizophrenia?

Research shows that non-invasive brain treatments, such as the investigational brainstem neuromodulation device used in this trial, may help treat schizophrenia. Previous studies found that this type of treatment can safely stimulate the brainstem. This trial includes an active treatment arm, where participants receive active stimulation, and a sham treatment arm for comparison. Researchers believe this stimulation helps people become more aware of their illness, which is often difficult for those with schizophrenia. While detailed results are still under study, early findings suggest that repeated use of this treatment could change brain activity in ways that improve illness awareness. These changes might help patients better understand and manage their condition. ^{1 2 3 4 5}

Who Is on the Research Team?

Philip Gerretsen, MD, PhD

Principal Investigator

Centre for Addiction and Mental Health

Are You a Good Fit for This Trial?

Adults diagnosed with schizophrenia or schizoaffective disorder, who have a moderate-to-severe lack of illness awareness and are stable on their current medications. Participants must be fluent in English, able to consent, and not planning medication changes during the study. Excluded are those with recent ear or eye surgery, active ear issues, severe medical conditions like heart disease or seizures, substance dependence (except caffeine/nicotine), pregnancy, vestibular dysfunction, metal implants/pacemakers affecting MRI scans.

Inclusion Criteria

Fluent in English

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

I've been on a steady dose of my psychiatric medication for 2 months.

Exclusion Criteria

I have been diagnosed with a balance disorder.

I currently have an ear infection or a ruptured eardrum.

I have not had eye surgery in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive twice-daily CVS or sham stimulation for 4 weeks

4 weeks

Daily visits (in-person or virtual)

Follow-up

Participants are monitored for changes in illness awareness and brain network activity

4 weeks

Weekly assessments (in-person or virtual)

Open-label extension

Participants may opt into receiving active stimulation for up to 12 weeks

Up to 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Investigational brainstem neuromodulation device

Trial Overview The trial is testing a non-invasive brainstem neuromodulation device to see if it can improve illness awareness in people with schizophrenia. It involves twice-daily sessions for four weeks and compares this treatment against a sham (fake) procedure. The effects will be measured through self-awareness assessments and brain imaging before and after the treatment period.

How Is the Trial Designed?

Group I: Open Label Experimental Treatment 1 Intervention

After completion of sham or active stimulation over 4 weeks, participants can choose to receive \~18-minute active stimulation twice daily for up to 12 weeks.

Group II: Active Treatment Active Control 1 Intervention

Study participants will receive \~18-minute active stimulation twice daily over 4 weeks, using a non-invasive brainstem modulation device.

Group III: Sham Treatment Placebo Group 1 Intervention

Study participants will receive \~18-minute of sham stimulation twice daily over 4 weeks using a non-invasive brainstem modulation device.

Who Is Running the Clinical Trial?

Centre for Addiction and Mental Health

Lead Sponsor

Trials

388

Recruited

84,200+

Scion NeuroStim

Industry Sponsor

Trials

14

Recruited

550+

Published Research Related to This Trial

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]

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]

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]

Deep brain stimulation is an effective treatment for movement disorders, involving an implanted electrode and pulse generator, but its mechanisms of action are not fully understood and were developed without extensive preclinical safety studies.

Complication rates for deep brain stimulation can exceed 25%, with 4-6% of patients experiencing permanent neurological issues, highlighting the need for better understanding of adverse events and safer stimulation methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety considerations for deep brain stimulation: review and analysis. Grill, WM.[2007]

Approximately one-third of patients with schizophrenia do not respond adequately to non-clozapine antipsychotics, and about half show poor response to clozapine and other treatments, highlighting the challenge of treatment-resistant schizophrenia (TRS).

The review discusses the potential of neuromodulation techniques, such as electroconvulsive therapy and transcranial magnetic stimulation, as promising treatments for TRS, and suggests that a precision medicine approach could improve outcomes by targeting the specific neurobiological pathways involved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dopaminergic dysfunction and excitatory/inhibitory imbalance in treatment-resistant schizophrenia and novel neuromodulatory treatment. Wada, M., Noda, Y., Iwata, Y., et al.[2022]

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]

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]

Deep brain stimulation (DBS) is an effective treatment for various disorders, including movement and epilepsy disorders, but it is vulnerable to external electromagnetic interference (EMI) that can cause device malfunction or tissue injury.

The study highlights the need for more comprehensive guidelines on EMI sources, as real-world instances of interference from devices like MRI scans and airport body scanners have been documented, indicating potential risks for patients with DBS devices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation and electromagnetic interference. Rahimpour, S., Kiyani, M., Hodges, SE., 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) 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]

Neuromodulation techniques, such as deep brain stimulation and transcranial magnetic stimulation, are emerging as potential treatment options for patients with psychiatric disorders who do not respond well to traditional drug therapy or psychotherapy.

The rationale behind using neuromodulation is based on research that identifies specific brain areas linked to persistent psychiatric symptoms, suggesting a targeted approach to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuromodulation in psychiatric disorders. Temel, Y., Hescham, SA., Jahanshahi, A., et al.[2012]

A review of 221 unique adverse events related to deep brain stimulation (DBS) devices for Parkinson's disease revealed that the most common complications were infections (16.2%) and lead migrations (8.6%).

Over 40% of the reported adverse events required patients to return to the operating room for device explantation or revision, highlighting the need for further research to improve the safety and reliability of DBS systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterizing Complications of Deep Brain Stimulation Devices for the Treatment of Parkinsonian Symptoms Without Tremor: A Federal MAUDE Database Analysis. Bennett, J., MacGuire, J., Novakovic, E., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05580211

NCT05580211 | Neuromodulation for Schizophrenia Study participants will receive ~19-minute treatments twice daily in the clinic setting over 4 weeks using a non-invasive brainstem modulation device.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05957484

The Effects of Non-invasive Neuromodulation on Illness ... Study participants will receive ~18-minute active stimulation twice daily over 4 weeks, using a non-invasive brainstem modulation device. Intervention/Treatment ...

3. trialx.com trialx.com/clinical-trials/listings/302459/neuromodulation-for-schizophrenia/

Neuromodulation for Schizophrenia The study device under investigation provides a safe and non-invasive method of brainstem stimulation that will be used in conjunction with ...

4. withpower.com withpower.com/trial/phase-schizophrenia-9-2022-5b459

Neuromodulation for Schizophrenia Trial Overview The study tests a non-invasive brainstem modulation device's effect on illness awareness in schizophrenia patients. It involves safe brain ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11103220/

Neuromodulation techniques – From non-invasive brain ... A study implemented anodal tDCS over the motor cortex, observing improvements in motor function [56], while another study demonstrated cognitive enhancement ...