This pilot study aims to investigate the use of MRI-guided low-intensity focused ultrasound (LIFU) to modulate neuronal activity within the thalamus in human subjects with treatment-resistant schizophrenia.
Approximately 30% of patients with schizophrenia have symptoms that persist despite multiple antipsychotic medication trials including clozapine, and there is currently no evidence-based treatment option for this population. These patients often suffer psychological distress related to their psychotic symptoms, become chronically disabled, and are unable to lead meaningful lives. Several promising new treatment modalities are being explored including deep brain stimulation (DBS) in subjects with treatment-resistant schizophrenia. A pilot study at another institution is using DBS of the substantia nigra pars reticulata (SNr) to modulate circuitry in the thalamus by disinhibiting the mediodorsal (MD) nucleus of the thalamus. This approach follows evidence from multiple structural and functional studies implicating hypofunction of the MD thalamus in the pathophysiology of schizophrenia. This includes an association between MD hypofunction and both positive and cognitive symptoms of schizophrenia including auditory hallucinations and working memory, respectively. As DBS is an invasive neurosurgical procedure with small but definable risks of neurologic injury, a minimally invasive screening method to optimize patient selection for DBS would be optimal. This pilot study aims to investigate the use of MRI-guided low-intensity focused ultrasound (LIFU) to modulate neuronal activity within the thalamus in human subjects with treatment-resistant schizophrenia. Focused ultrasound itself is a safe, incisionless technology with high spatial resolution and depth penetration that has been shown to stimulate and inhibit neuronal activity. At high intensities, focused ultrasound can be used to thermally ablate a specific region of brain tissue and has been FDA-approved for the treatment of essential tremor and tremor in Parkinson's disease via thermal ablation of the ventral intermediate (VIM) thalamus. In contrast, LIFU is non-ablative and thus can be used for transient neuromodulation with high spatial precision due to direct real-time MRI targeting. This pilot study aims to use non-ablative LIFU to target the MD thalamus noninvasively and specifically, with the aim of interrogating and modulating the neuronal circuitry involved in symptoms of schizophrenia.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
3
This study will be utilizing the Insightec Exablate Neuro MR-guided focused ultrasound transducer to deliver low-intensity ultrasonic energy precisely and safely to the target region of the brain. MRgFUS has been FDA approved at high-intensity to treat essential tremor and Parkinson's disease associated tremor. Device premarket approval number (PMA) is P150038, and FDA approval notice was July 11, 2016. This study will be using this device not to make any lesions in the brain (as it is currently FDA approved), but instead to use the precision and non-invasive nature of the device to target the MD thalamus region of the brain at intensities currently approved by the FDA for transcranial ultrasound.
NYU Langone Health
New York, New York, United States
Number of Patients who Complete All Visits Related to the Study
Measurement of feasibility of low-intensity focused ultrasound (LIFU) for treatment-resistant schizophrenia. Feasibility defined as two out of three patients completing all visits related to the study.
Time frame: Up to Month 3
Change in Brief Psychiatric Rating Scale (BPRS) Score from Baseline
BPRS is a measurement of the severity of schizophrenia. It assesses the level of 18 symptom constructs including hostility, suspiciousness, hallucination, and grandiosity. The rater enters a number for each symptom construct that ranges from 1 (not present) to 7 (extremely severe), while items that are not assessed are scored as 0. The total score is the sum of responses and ranges from 18 to 126; higher scores indicate greater severity of symptoms.
Time frame: Baseline, Month 3
Change in Positive and Negative Syndrome Scale (PANSS) Score from Baseline
PANSS is a 30-item medical scale used for measuring symptom severity of patients with schizophrenia. Items are rated on a 7-point scale (1=absent, 2=minimal, 3=mild, 4=moderate, 5=moderate severe, 6=severe, and 7=extreme). The total score is the sum of responses and ranges from 30 to 210; higher scores indicate greater illness severity.
Time frame: Baseline, Month 3
Change in Montreal Cognitive Assessment (MoCA) Score from Baseline
MoCA is a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. The total score is the sum of responses and ranges from 0 to 30; higher scores indicate less cognitive dysfunction. A normal score is defined as greater than or equal to 26.
Time frame: Baseline, Month 3
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