Non-invasive Neuromodulation for Schizophrenia
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: N/A
Recruiting
Sponsor: Centre for Addiction and Mental Health
Approved in 1 jurisdiction
Trial Summary
What is the purpose of this trial?This study aims to determine the clinical and functional imaging effects of serial CVS on illness awareness in schizophrenia. Specifically, the investigators aim to:
1. Determine if twice-daily CVS for 4 weeks will improve illness awareness compared to the sham condition in participants with schizophrenia. Illness awareness will be assessed at pre- and post-CVS, and weekly thereafter for 4 weeks.
2. Examine changes in brain network activity (blood oxygen level dependent-BOLD in response to an illness awareness task) pre- and post-CVS. This will serve as a biomarker to rigorously test whether repeated CVS engages the PPA associated with illness awareness.
What data supports the idea that Non-invasive Neuromodulation for Schizophrenia is an effective treatment?The available research shows that non-invasive brain stimulation has been promising for patients with schizophrenia who do not respond to traditional treatments. However, the studies on its effectiveness are limited and often lack consistent reporting, making it hard to draw strong conclusions. Compared to other treatments like antipsychotic drugs, which often fail to help a significant number of patients, non-invasive neuromodulation offers a potential alternative, especially for those with treatment-resistant symptoms. Despite its potential, more high-quality studies are needed to confirm its effectiveness.28101112
Do I have to stop taking my current medications for this trial?No, you don't have to stop taking your current medications. Participants must be on a stable dose of antipsychotic and other medications for at least 2 months before the study and are unlikely to change doses during the study.
Is non-invasive neuromodulation a promising treatment for schizophrenia?Yes, non-invasive neuromodulation is a promising treatment for schizophrenia. It has shown potential in helping patients who do not respond well to traditional treatments, especially for symptoms like hallucinations and cognitive issues. This approach is gaining attention for its ability to improve brain function and reduce symptoms.2361012
What safety data exists for non-invasive neuromodulation treatment for schizophrenia?The study on transcutaneous noninvasive vagus nerve stimulation (tVNS) for schizophrenia found that the treatment was well tolerated with no relevant adverse effects. However, it did not show significant improvement in schizophrenia symptoms. The study suggests that while tVNS is safe, its efficacy in treating schizophrenia needs further investigation. Other studies on deep brain stimulation (DBS), a different form of neuromodulation, report complications such as infections, lead migrations, and device malfunctions, but these are related to invasive procedures, not non-invasive ones like tVNS.14579
Eligibility Criteria
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
I have been diagnosed with schizophrenia or schizoaffective disorder.
Exclusion Criteria
I currently have an ear infection or a ruptured eardrum.
I have been diagnosed with a balance disorder.
I have not had eye surgery in the last 3 months.
I do not have any severe illnesses like heart disease or epilepsy.
Treatment Details
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.
3Treatment groups
Experimental Treatment
Active Control
Placebo Group
Group I: Open LabelExperimental Treatment1 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 TreatmentActive Control1 Intervention
Study participants will receive \~18-minute active stimulation twice daily over 4 weeks, using a non-invasive brainstem modulation device.
Group III: Sham TreatmentPlacebo Group1 Intervention
Study participants will receive \~18-minute of sham stimulation twice daily over 4 weeks using a non-invasive brainstem modulation device.
Find a clinic near you
Research locations nearbySelect from list below to view details:
Centre for Addiction and Mental HealthToronto, Canada
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Who is running the clinical trial?
Centre for Addiction and Mental HealthLead Sponsor
Scion NeuroStimIndustry Sponsor
References
Safety considerations for deep brain stimulation: review and analysis. [2007]Deep brain stimulation has emerged rapidly as an effective therapy for movement disorders. Deep brain stimulation includes an implanted brain electrode and a pacemaker-like implanted pulse generator. The clinical application of deep brain stimulation proceeded in the absence of clear understandings of its mechanisms of action or extensive preclinical studies of safety and efficacy. Post mortem studies suggest that there is a loss of neurons in proximity to the active electrode, but the resulting lesions are not sufficient to treat the disorder and efficacy requires continued stimulation. Overall complication rates can exceed 25%, and permanent neurologic sequelae result in 4-6% of cases. As the application of deep brain stimulation expands, it is critical to understand the origin of adverse events and the delivery of nondamaging stimulation.
Neuromodulation in psychiatric disorders. [2012]Psychiatric disorders are worldwide a common cause of severe and long-term disability and socioeconomic burden. The management of patients with psychiatric disorders consists of drug therapy and/or psychotherapy. However, in some patients, these treatment modalities do not produce sufficient therapeutic effects or induce intolerable side effects. For these patients, neuromodulation has been suggested as a potential treatment modality. Neuromodulation includes deep brain stimulation, vagal nerve stimulation, and transcranial magnetic and electrical stimulation. The rationale for neuromodulation is derived from the research identifying neurobiologically localized substrates for refractory psychiatric symptoms. Here, we review the clinical data on neuromodulation in the major psychiatric disorders. Relevant data from animal models will also be discussed to explain the neurobiological basis of the therapy.
Modulating neural plasticity with non-invasive brain stimulation in schizophrenia. [2022]Schizophrenia is a severe mental disorder characterised by a complex phenotype including positive, negative, affective and cognitive symptoms. Various theories have been developed to integrate the clinical phenotype into a strong neurobiological framework. One theory describes schizophrenia as a disorder of impaired neural plasticity. Recently, non-invasive brain stimulation techniques have garnered much attention to their ability to modulate plasticity and treat schizophrenia. The aim of this review is to introduce the basic physiological principles of conventional non-invasive brain stimulation techniques and to review the available evidence for schizophrenia. Despite promising evidence for efficacy in a large number of clinical trials, we continue to have a rudimentary understanding of the underlying neurobiology. Additional investigation is required to improve the response rates to non-invasive brain stimulation, to reduce the interindividual variability and to improve the understanding of non-invasive brain stimulation in schizophrenia.
Transcutaneous noninvasive vagus nerve stimulation (tVNS) in the treatment of schizophrenia: a bicentric randomized controlled pilot study. [2018]Despite many pharmacological and psychosocial treatment options, schizophrenia remains a debilitating disorder. Thus, new treatment strategies rooted in the pathophysiology of the disorder are needed. Recently, vagus nerve stimulation (VNS) has been proposed as a potential treatment option for various neuropsychiatric disorders including schizophrenia. The objective of this study was to investigate for the first time the feasibility, safety and efficacy of transcutaneous VNS in stable schizophrenia. A bicentric randomized, sham-controlled, double-blind trial was conducted from 2010 to 2012. Twenty schizophrenia patients were randomly assigned to one of two treatment groups. The first group (active tVNS) received daily active stimulation of the left auricle for 26 weeks. The second group (sham tVNS) received daily sham stimulation for 12 weeks followed by 14 weeks of active stimulation. Primary outcome was defined as change in the Positive and Negative Symptom Scale total score between baseline and week 12. Various other secondary measures were assessed to investigate safety and efficacy. The intervention was well tolerated with no relevant adverse effects. We could not observe a statistically significant difference in the improvement of schizophrenia psychopathology during the observation period. Neither psychopathological and neurocognitive measures nor safety measures showed significant differences between study groups. Application of tVNS was well tolerated, but did not improve schizophrenia symptoms in our 26-week trial. While unsatisfactory compliance questions the feasibility of patient-controlled neurostimulation in schizophrenia, the overall pattern of symptom change might warrant further investigations in this population.
Managing Negative Symptoms of Schizophrenia: How Far Have We Come? [2018]The specific efficacy of antipsychotics on negative symptoms is questionable, suggesting an urgent need for specific treatments for negative symptoms. This review includes studies published since 2014 with a primary or secondary focus on treating negative symptoms in schizophrenia. Special emphasis is given to recently published meta-analyses. Topics include novel pharmacological approaches, including glutamatergic-based and nicotinic-acetylcholinergic treatments, treatments approved for other indications by the US FDA (or other regulatory bodies) (antipsychotics, antidepressants, and mood stabilizers), brain stimulation, and behavioral- and activity-based approaches, including physical exercise. Potential complications regarding the design of current negative symptom trials are discussed and include inconsistent placebo effects, lack of reliable biomarkers, negative symptom scale and inclusion criteria variability, attempts to distinguish between primary and secondary negative symptoms, lack of focus on early psychosis, and the potential iatrogenic bias of clinical trials.
[Brain stimulation for the selective treatment of schizophrenia symptom domains : Non-invasive and invasive concepts]. [2020]Given that one third of patients with schizophrenia (SZ) only show limited response to established treatments, alternative therapeutic strategies such as non-invasive/invasive brain stimulation approaches have emerged as an adjunctive treatment option for distinct SZ symptom domains (e.g. acoustic hallucinations, negative/positive symptoms and cognitive impairment). Taking comparative interventional studies and standardized technical parameters into consideration, current meta-analyses indicate that adjunctive electroconvulsive therapy, repetitive transcranial magnetic stimulation and transcranial direct current stimulation have a positive effect. Invasive deep brain stimulation and MR-guided ultrasound brain ablation procedures represent treatment modalities that are currently being clinically tested. Complementary pre-interventional screening approaches (e.g. electrophysiology, neuroimaging and molecular inflammatory profiling) have been recommended in order to identify symptom-tailored predictive measures for diagnosis and treatment.
Deep brain stimulation and electromagnetic interference. [2022]Deep brain stimulation (DBS) has evolved into an approved and efficacious treatment for movement, obsessive-compulsive, and epilepsy disorders that are refractory to medical therapy, with current investigation into other disease conditions. However, there are unintentional and intentional sources of external electromagnetic interference (EMI) that can lead to either malfunctioning or damaged DBS devices, as well as injury to human tissue. Comprehensive studies and guidelines on such topics in the medical literature are scarce. Herein, we review the principles behind EMI, as well as the various potential sources of interference, both unintentional (e.g. stray EMI fields) and intentional (e.g. MRI scans, "brainjacking"). Additionally, we employ the Manufacturer and User Device Facility Experience (MAUDE) database to assess real-world instances of EMI (e.g., airport body scanners, magnetic resonance imaging (MRI), and electrosurgery) affecting DBS devices commonly implanted in the United States (US).
Assessment of treatment resistance criteria in non-invasive brain stimulation studies of schizophrenia. [2022]Novel treatment modalities, such as non-invasive brain stimulation (NIBS), typically focus on patient groups that have failed multiple treatment interventions. Despite its promise, the clinical translation of NIBS in schizophrenia has been limited. One important obstacle to implementation is the inconsistent reporting of treatment resistance in the clinical trial literature contributing to heterogeneity in reported effects. In response, we develop a numerical approach to synthesize quality of assessment of Treatment-Resistant Schizophrenia (TRS) and apply this to studies investigating therapeutic response to NIBS in patients with schizophrenia. Literature search conducted through PubMed database identified 119 studies investigating Transcranial Magnetic Stimulation and Transcranial Electrical Stimulation in treating resistant schizophrenia symptoms. A quality score out of 11 was assigned to each study based on adherence to the international consensus guidelines for TRS developed by the Treatment Response and Resistance in Psychosis (TRRIP) group. Results revealed an overall paucity of studies with thorough assessment and/or reporting of TRS phenomenon, as evidenced by a mean quality score of 3.38/11 (SD: 1.01) for trials and 5.16/11 (SD: 1.57) for case reports, though this improved minimally since the publication of consensus criteria. Most studies considered treatment-resistance as a single dimensional construct by reporting resistance of a single symptom, and failed to establish treatment adherence, resistance time course and functional impairment. We conclude that the current NIBS literature in schizophrenia do not reflect its true effects on treatment-resistance. There is an urgent need to improve assessment and reporting standards of clinical trials that target TRS.
Characterizing Complications of Deep Brain Stimulation Devices for the Treatment of Parkinsonian Symptoms Without Tremor: A Federal MAUDE Database Analysis. [2023]Introduction Deep brain stimulation (DBS) is a modality of treatment for medication refractory Parkinson's disease (PD) in patients with debilitating motor symptoms. While potentially life-changing for individuals with Parkinson's disease, characterization of adverse events for these DBS devices have not yet been systematically organized. Therefore, the goal of this study was to characterize reported complications of DBS devices reported to the Food & Drug Administration over the last 10 years. Methods The Manufacturer and User Facility Device Experience (MAUDE) database was utilized to retrieve entries reported under "Stimulator, Electrical, Implanted, For Parkinsonian Symptoms" between July 31, 2010 and August 1, 2020. After removing duplicate entries, each unique adverse event reported was sorted into complication categories based on the entries' provided narrative description. A final tabulation of complications was generated. Results The search query revealed 221 unique adverse events. The most common DBS devices were the Vercise Gevia, Vercise Cartesia and Vercise PC produced by Boston Scientific (Brian Walker, Boston Scientific, Marlborough, MA, USA). The most commonly reported complications were infection (16.2%) follow by lead migrations (8.6%). Other common causes of complications were circuit-related impedance (6.5%), cerebral bleeds (6.3%), device failure (6.3%) and device-related trauma (4.5%). Over a third (40%) of all devices reported with adverse events required returning to the operating room for explant or revision. Conclusion The most common complications of DBS systems are infections followed by lead migrations. Further research is needed to minimize infection rates associated with DBS systems and to reduce intrinsic device malfunctions for patients in the future.
Neuromodulation to Treat Substance Use Disorders in People With Schizophrenia and Other Psychoses: A Systematic Review. [2022]Substance use disorders (SUDs) are a common yet poorly studied comorbidity in individuals with psychotic disorders. The co-occurrence of the two complicates recovery and interferes with pharmacological and behavioral treatment response and adherence. Recently, researchers have been exploring both invasive and non-invasive neuromodulation techniques as potential treatment methods for SUDs. We review the evidence that neuromodulation may reduce substance craving and consumption in individuals with schizophrenia.
Dopaminergic dysfunction and excitatory/inhibitory imbalance in treatment-resistant schizophrenia and novel neuromodulatory treatment. [2022]Antipsychotic drugs are the mainstay in the treatment of schizophrenia. However, one-third of patients do not show adequate improvement in positive symptoms with non-clozapine antipsychotics. Additionally, approximately half of them show poor response to clozapine, electroconvulsive therapy, or other augmentation strategies. However, the development of novel treatment for these conditions is difficult due to the complex and heterogenous pathophysiology of treatment-resistant schizophrenia (TRS). Therefore, this review provides key findings, potential treatments, and a roadmap for future research in this area. First, we review the neurobiological pathophysiology of TRS, particularly the dopaminergic, glutamatergic, and GABAergic pathways. Next, the limitations of existing and promising treatments are presented. Specifically, this article focuses on the therapeutic potential of neuromodulation, including electroconvulsive therapy, repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and deep brain stimulation. Finally, we propose multivariate analyses that integrate various perspectives of the pathogenesis, such as dopaminergic dysfunction and excitatory/inhibitory imbalance, thereby elucidating the heterogeneity of TRS that could not be obtained by conventional statistics. These analyses can in turn lead to a precision medicine approach with closed-loop neuromodulation targeting the detected pathophysiology of TRS.
Recent advances in noninvasive brain stimulation for schizophrenia. [2023]Noninvasive brain stimulation has emerged in the last three decades as a promising treatment for patients with antipsychotic-resistant symptoms of schizophrenia. This review updates the latest progress in the use of noninvasive brain stimulation to treat schizophrenia symptoms.