Neuromodulation for Schizophrenia
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Scion NeuroStim
Must be taking: Antipsychotics
Disqualifiers: Cardiovascular disease, Seizures, Substance dependence, others
No Placebo Group
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.
12345Is 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.
12367How 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.
248910Eligibility 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
+3 more
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
+10 more
Trial 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
Participant Groups
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.
3Treatment groups
Experimental Treatment
Group I: Investigational Stimulation Pattern-Open LabelExperimental Treatment1 Intervention
Group II: Investigational Stimulation Pattern 2-RandomizedExperimental Treatment1 Intervention
Group III: Investigational Stimulation Pattern 1-RandomizedExperimental Treatment1 Intervention
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?
Scion NeuroStimLead Sponsor
Centre for Addiction and Mental HealthCollaborator
References
[Non-invasive brain stimulation for treatment of schizophrenic psychoses]. [2018]Despite many different available pharmacological and psychosocial treatment options, an optimal control of symptoms is only partly possible for most schizophrenia patients. Especially, persistent auditory hallucinations, negative symptoms and cognitive impairment are difficult to treat symptoms. Several non-invasive brain stimulation techniques are increasingly being considered as new therapeutic add on options for the management of schizophrenia, targeting these symptom domains. The technique which has been available for the longest time and that is best established in clinical care is electroconvulsive therapy (ECT). New stimulation techniques, such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) allow a more pathophysiological-based approach. This review article introduces various non-invasive brain stimulation techniques and discusses recent treatment studies on schizophrenia. In total, the novel brain stimulation techniques discussed here can be considered relevant add on therapeutic approaches for schizophrenia. In this context, the best evidence is available for the application of rTMS for the treatment of negative symptoms and persistent auditory hallucinations; however, negative studies have also been published for both indications. Studies using other non-invasive brain stimulation techniques showed promising results but further research is needed to establish the clinical efficacy. Based on a growing pathophysiological knowledge, non-invasive brain stimulation techniques provide new treatment perspectives for patients with schizophrenia.
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.
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.
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.
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.
Moderate effects of noninvasive brain stimulation of the frontal cortex for improving negative symptoms in schizophrenia: Meta-analysis of controlled trials. [2019]Negative symptoms in schizophrenia concern a clinically relevant reduction of goal-directed behavior that strongly and negatively impacts daily functioning. Existing treatments are of marginal effect and novel approaches are needed. Noninvasive neurostimulation by means of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are novel approaches that may hold promise.
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.
Electroconvulsive Therapy and Other Neuromodulation Techniques for the Treatment of Psychosis. [2019]Electroconvulsive therapy is an established treatment for symptoms of psychosis and is currently recommended for use in patients who are experiencing an acute exacerbation of positive symptoms or who have had catatonia. There is also evidence to suggest that electroconvulsive therapy can be a safe, effective treatment in first episode psychosis, such as schizophrenia spectrum disorders, particularly in treatment-resistant patients. Other forms of neuromodulation (transcranial magnetic stimulation, transcranial direct current stimulation, vagus nerve stimulation, deep brain stimulation) have less of an evidence base to support their use and are not formally indicated for the treatment of psychosis.
Non-pharmacological biological therapies in schizophrenia. [2018]Non-pharmacological biological therapies of schizophrenia have dramatically developed over the last eight decades. Starting from a historical perspective authors aim to give an overview about the development of convulsive therapy. Recommendations of the most influential guidelines and the controversies in the worldwide clinical practice are discussed and clinical conditions responsive to electroconvulsive therapy are reviewed. Finally, the place of the new neurostimulation techniques, particularly TMS is outlined.
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.