.An Open-label Clinical Trial Evaluating the ExAblate Model 4000 Type-1 Focused Ultrasound Unilateral Thalamotomy for Patients With Treatment-refractory Focal Onset Epilepsy and Comorbid Anxiety.
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Change in Anxiety symptoms
研究概览
简要总结
The purpose of this study is to evaluate the feasibility, safety, and effects on anxiety of high intensity focused ultrasound ablation (FUSA) in patients suffering from treatment-refractory focal epilepsy and anxiety. FUSA is a non-invasive neurosurgical procedure that uses ultrasound waves, sent directly through the scalp and skull, to precisely target small abnormal areas of the brain. For this study, the targeted area of the brain is the anterior nucleus of the thalamus. This brain region may cause seizures and may also be involved in anxiety. The study will test if FUSA is safe and tolerated, and if it reduces anxiety and brain response to threat in patients with anxiety receiving the procedure for partial-onset epilepsy that is resistant to medications.
详细描述
This is an open-label, Phase 1 prospective intervention study. Ten (10) adults with refractory, partial-onset epilepsy with moderate-severe anxiety and able to provide informed consent will be enrolled.
Patients, eligible for Magnetic Resonance Imaging-guided Focused Ultrasound Ablation (MRgFUSA) of the anterior nucleus of the thalamus (ATN) for treatment-refractory epilepsy and who present moderate-severe anxiety will be enrolled. In addition to the diagnosis of medically refractory epilepsy, patients will need to present moderate to severe anxiety (as measured by the Hamilton Anxiety Rating Scale, HAM-A; HAMA score > 17) and other protocol specific inclusion and exclusion criteria.
Medication-refractory partial or focal-onset epilepsy is often associated with enhanced fear behaviors and clinical anxiety. Exaggerated amygdala reactivity to threat is a cardinal neural phenotype of fear and anxiety disorders. The study will determine if MRgFUSA-ATN is feasible and safe and its effects on anxiety, using neuroimaging and neurological, neurocognitive/neuropsychological, psychiatric assessments before, and 1 day, 1 week, 1 month, 3 months, 6 months and 12 months post MRgFUSA.
Feasibility is defined as the ability to create the desired lesion within the anterior nucleus of the thalamus and perform fMRI to measure threat reactivity.
Safety will be measured by recording and analyzing any adverse effects that may occur from before surgery through 12 months following the surgery. These will include any new onset of neurological deficits, or performance deterioration on neuropsychological testing.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Disabling, medically refractory epilepsy (≥2 anti-epileptic drug failures).
- •Focal onset seizures with secondary generalization; with or without primary generalized seizures.
- •Previous seizure work-up within 12 months of enrollment date to include:
- •A. Home EEG or EMU video EEG or intracranial EEG. B. High definition MRI imaging/PET imaging. C. Baseline neuropsychological assessment, which includes the Wechsler Advanced Clinical Solutions - Test of Premorbid Functioning (TOPF).
- •≥ 3 seizures/month on average within 3 months of enrollment.
- •Stable medication (including anti-epileptic and psychotropic/psychoactive medications) dosage for 3 months before enrollment.
- •Moderate-severe anxiety as measured by the Hamilton Anxiety Rating Scale (HAM-A) score >
- •Anterior Nucleus (AN) identifiable on MRI (structural T1 and T2 images).
- •Willing to maintain seizure diary (3 months before & 3 months after).
- •Involved care provider.
- •Written informed consent to participate.
- •Ability to comply with all testing, follow-ups, and study appointments and protocols.
排除标准
- •Low seizure frequency (<3 seizures/month).
- •Generalized epilepsy (Lennox Gastaut, drop attacks).
- •Post infectious epilepsy (post herpetic).
- •Unable or unwilling to maintain anti-epilepsy drug dosage for 3 months post treatment.
- •Active (current in past 12 months), uncontrolled DSM-5 psychiatric disorder, except for anxiety disorders.
- •Recent (past 12 months) history of drugs or alcohol abuse as evidenced by diagnosis of Substance Use Disorder.
- •Active suicidal ideation current and past 30 days.
- •Clinically significant neurological disorder, except for epilepsy.
- •Presence of any neurodegenerative disease suspected on neurological examination. These include but are not limited to: Multisystem atrophy; Progressive supranuclear palsy; Dementia with Lewy bodies; Alzheimer's disease; Parkinson's disease.
- •Cerebrovascular disease (multiple CVA or CVA within six months).
- •Significant structural brain abnormalities.
- •Surgical lesion identifiable on imaging.
- •Symptoms and signs of increased intracranial pressure.
- •Patients with any types of brain tumors, including metastases.
- •Previous vagal nerve stimulator.
- •Previous corpus callosotomy.
- •Patients who have had deep brain stimulation.
- •Prior stereotactic ablation.
- •Positive urine drug screen at study entry or any follow-up testing session. For cannabis, exclusion includes positive drug screen with self-report of cannabis use in the past 48 hours.
- •Known allergic reaction and/or hypersensitivity to IV dye and/or IV contrasting agent(s).
- •Patients with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices including cardiac pacemakers, size limitations, etc.
- •History of claustrophobia.
- •Unstable cardiac status including: Unstable angina pectoris on medication; documented myocardial infarction within last 40 days to protocol entry; Congestive heart failure; Severe hypertension (diastolic BP> 100 on medication).
- •Patients receiving dialysis;
- •Patients with risk factors for intraoperative or postoperative bleeding: Platelet count less than 100,000 per cubic millimeter; PT> 14PTT > 40; INR > 1.
- •History of abnormal bleeding and/or coagulopathy.
- •Receiving anticoagulant (e.g., Warfarin) or antiplatelet (e.g., aspirin) therapy within one week of focused ultrasound procedure or drugs known to increase risk of hemorrhage (e.g., Avastin) within one month of scheduled focused ultrasound procedure.
- •History of intracranial hemorrhage.
- •Active or suspected, acute or chronic uncontrolled infection or known life-threatening systemic disease;
- •History of immunocompromised status, including patients who are HIV positive.
- •Subjects with remarkable atrophy and poor healing capacity of the scalp.
- •Evidence for calcifications that might interfere with treatment safety (per CT).
- •Skull Density Ratio (SDR) <0.
- •Pregnancy or lactation or planning to become pregnant during the time-period of the study.
- •Any illness that in the investigators' opinion preclude participation in this study.
- •Individuals who are not able or willing to tolerate the required prolonged stationary supine position during treatment (can be up to 4 hrs of total table time);
- •IQ score of <70 on the Wechsler Advanced Clinical Solutions - Test of Premorbid Functioning (TOPF), measured as part of screening neuropsychological assessment.
- •Presence of significant cognitive impairment as determined with a score ≤24 on the Mini Mental Status Examination (MMSE).
- •Patients unable to communicate with the investigator and staff.
- •Legal incapacity or limited legal capacity.
研究组 & 干预措施
Intervention
Unilateral Magnetic Resonance Imaging-guided Focused Ultrasound Ablation (MRgFUSA) of the anterior nucleus of the thalamus (ATN)
干预措施: Magnetic Resonance Imaging-guided Focused Ultrasound Ablation (MRgFUSA) (Device)
结局指标
主要结局
Change in Anxiety symptoms
时间窗: 12 months
Change in anxiety symptoms will be measured using clinician-administered HAM-A scale before the procedure and at various time points after the procedure. HAM-A is the scale of reference used in clinical trials to rate the severity of symptoms of anxiety in patients. It will be collected before and after the procedure at day 1, 7, months 1, 3, 6 and 12 to determine any effect and its change overtime.
Target
时间窗: 1 month
Feasibility will be determined by ability to create the desired lesion within the anterior nucleus of the thalamus as assessed by neuroimaging
Effect on Threat Reactivity
时间窗: 1 day
Change in Threat reactivity measured by fMRI task just before and after MRgFUSA
Incidence of Treatment-Emergent Adverse Events
时间窗: 12 months
Safety will be determined by an evaluation of the incidence and severity of MRgFUSA-ATN and other research procedures related adverse events from the 1st study visit through the 12-month post-treatment time point. Post-procedural imaging will be evaluated for evidence of swelling, hemorrhage, and the evolution of the ATN lesion. Emergence of complications will be monitored by neurological examination at day 1, day 7, month 1, month 3, month 6 and month 12 post-procedure. A comprehensive battery of neuropsychological assessments will be conducted by board-certified neuropsychologists at study screening, 3-month and 12-month postoperative time points. All events that are not procedure related will also be captured and recorded.
次要结局
- Change in quality of life(12 months)
- Change in seizure frequency(12 months)
- Ability to perform the threat reactivity fMRI task just before and after MRgFUSA(4 years)
- Rate of Patient Accrual(4 years)
- Change in self-reported anxiety symptoms(12 months)
研究者
Kinh Luan Phan
Professor, Department of Psychiatry
Ohio State University