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A Feasibility Study to Evaluate Safety and Initial Effectiveness of ExAblate Transcranial MR Guided Focused Ultrasound for Unilateral Thalamotomy in the Treatment of Medication-Refractory Tremor Dominant Idiopathic Parkinson's Disease. (PD001J)

PD001J (PD001J)

10

10cases SexAge 1m72 2f58 3m72 4f74 5f62 6f71 7m78 8f77 9m63 10f74

Summary of results Breakdown of registered cases Target number of cases: 10 cases Consent cases: 14 cases Cumulative number of cases: 10 cases Number of completed cases: 10 cases Number of discontinued cases: 0 cases Incidents subject to compensation 1 case

3 serious safety events ( left hemiplegia, urinary tract infection,fracture) occurred. Left hemiplegia with prolonged hospitalization were causally related and covered by the compensation.

Major Endpoint 19adverse events were identified during the clinical study. Of these, 9 (47%) were mild, 9 (47%) were moderate, and 1 (5%) was severe.Three serious adverse events were identified (left hemiplegia, urinary tract infection, fracture). Secondary Endpoint Regarding the Medication Arm Tremor Score (CRST) score, the severity, as measured by the PART A subsection, decreased most by 83.6% after 3 months. After 12 months, it was 26.3%, but initial efficacy was observed.

19adverse events were identified during the clinical study. Of these, 9 (47%) were mild, 9 (47%) were moderate, and 1 (5%) was severe.Three serious adverse events were identified (left hemiplegia, urinary tract infection, fracture).The left hemiplegia was relieved, but there was a causal relationship with this treatment, and it was eligible for compensation.

Sept. 06, 2023

No

No

https://jrct.mhlw.go.jp/latest-detail/jRCTs032180081

KAMEI TETSUMASA

Medical Corporation Tokushukai Shonanfujisawa Tokushukai Hospital

1-5-1 Kandai Tsujido Fujisawa Kanagawa Japan

tetsumasakam@ctmc.jp

SHIMIZU ETSUKO

Medical Corporation Tokushukai Shonanfujisawa Tokushukai Hospital

1-5-1 Kandai Tsujido Fujisawa Kanagawa Japan

+81-466-35-1177

etsuko.shimizu@tokushukai.jp

Complete

Jan. 19, 2017

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

01 Men and women, age 20 years and older. 02 Subjects who are able and willing to give informed consent and able to attend all study visits. 03 Subjects with a diagnosis of idiopathic PD as confirmed from clinical history and examination by a movement disorder neurologist at the site. 04 All subjects included in this study will have a TD/PIGD ratio > 1.15 in the medicated [ON] state as calculated from the UPDRS formula as described by S, et. al., [74]. 05 Subject demonstrates a resting tremor severity score of greater than or equal to 3 in the hand/arm as measured by the medicated (ON) MDS-UPDRS question 3.17 or a postural/action tremor greater than or equal to a 2 for question 3.15 or 3.16. 06 Significant disability due to PD tremor despite medical treatment (CRST score of 2 or above in any one of the items 16-23 from the Disability subsection of the CRST: [speaking, feeding other than liquids, bringing liquids to mouth, hygiene, dressing, writing, working, and social activities.]) 07 Tremor remains disabling when medical therapy is optimal or not tolerated for the treatment of other cardinal signs of PD (bradykinesia, rigidity, etc), as determined by a movement disorders neurologist at the site. 08 Subjects should be on a stable dose of all PD medications for 30 days prior to study entry. 09 The thalamus must be apparent on MRI such that targeting of the Vim nucleus can be performed indirectly by measurement from a line connecting the anterior and posterior commissures of the brain. 10 Subject is able to communicate sensations during the ExAblate Transcranial procedure.

01 Subjects with unstable cardiac status including: a)Unstable angina pectoris on medication. b)Subjects with documented myocardial infarction within six months of protocol entry c)Significant congestive heart failure defined with ejection fraction < 40. d)Subjects with unstable ventricular arrhythmias. e)Subjects with atrial arrhythmias that are not rate-controlled. 02 Subjects exhibiting any behavior(s) consistent with ethanol or substance abuse as defined by the criteria outlinnyuued in the DSM-IV as manifested by one (or more) of the following occurring within the preceding 12 month period: a)Recurrent substance use resulting in a failure to fulfill major role obligations at work, school, or home (such as repeated absences or poor work performance related to substance use; substance-related absences, suspensions, or expulsions from school; or neglect of children or household). b)Recurrent substance use in situations in which it is physically hazardous.(such as driving an automobile or operating a machine when impaired by substance use) c)Recurrent substance-related legal problems.(such as arrests for substance related disorderly conduct) d)Continued substance use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the substance (for example, arguments with spouse about consequences of intoxication and physical fights). 03 Severe hypertension (diastolic BP > 100 on medication.) 04 Subjects with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices including cardiac pacemakers, size limitations, etc. 05 Significant claustrophobia that cannot be managed with mild medication. 06 Current medical condition resulting in abnormal bleeding and/or coagulopathy. 07 Patient with severely impaired renal function with estimated glomerular filtration rate <30mL/min/1.73m2 (or per local standards should that be more restrictive) and/or who is on dialysis; 08 Receiving anticoagulant (e.g. warfarin) or antiplatelet (e.g. aspirin) therapy within one week of focused ultrasound procedure or drugs known to increase risk or hemorrhage (e.g. Avastin) within one month of focused ultrasound procedure. 09 Subjects with risk factors for intraoperative or postoperative bleeding as indicated by: platelet count less than 100,000 per cubic millimeter, a documented clinical coagulopathy, or INR coagulation studies exceeding the institutions laboratory standard. 10 History of intracranial hemorrhage. 11 History of multiple strokes, or a stroke within past 6 months. 12 Subject who weigh more than the upper weight limit of the table or subjects who will not fit into the MR scanner. 13 Subjects who are not able or willing to tolerate the required prolonged stationary supine position during treatment. 14 Are participating or have participated in another clinical trial in the last 30 days. 15 Subjects unable to communicate with the investigator and staff. 16 Presence of central neurodegenerative disease, including but not limited to Parkinson-plus syndromes, suspected on neurological examination. These include: multisystem atrophy, progressive supranuclear palsy, corticobasal syndrome, dementia with Lewy bodies, and Alzheimers disease. 17 Any suspicion that Parkinsonian symptoms are a side effect from neuroleptic medications. 18 Presence of significant cognitive impairment as determined with a score < 24 on the MMSE(Mini-Mental State Examination ). 19 Unstable psychiatric disease, defined as active uncontrolled depressive symptoms, psychosis, delusions, hallucinations, or suicidal ideation. Subjects with stable, chronic anxiety or depressive disorders may be included provided their medications have been stable for at least 60 days prior to study entry and if deemed appropriately managed by the site neuropsychologist. 20 Subjects with significant depression as determined following a comprehensive assessment by a neuropsychologist. Significant depression is being defined quantitatively as a score of greater than 14 on the Beck Depression Inventory. 21 Legal incapacity or limited legal capacity as determined by the neuropsychologist. 22 Subjects with a history of seizures within the past year. 23 Subjects with brain tumors. 24 Subjects with intracranial aneurysms requiring treatment or arterial venous malformations (AVMs) requiring treatment. 25 Any illness that in the investigators opinion preclude participation in this study. 26 Pregnancy or lactation. 27 Subjects who have had deep brain stimulation or a prior stereotactic ablation of the basal ganglia. 28 Subjects with remarkable atrophy and poor healing capacity of the scalp (> 30% of the skull area traversed by the sonication pathway) will be excluded from this study. 29 Subjects who have an Overall Skull Density Ratio of 0.30 (+-0.05) or less as calculated from the screening CT.

Both

Medication-Refractory Tremor Dominant Idiopathic Parkinsons Disease

ExAblate Transcranial MRgFUS Thalamotomy Treatment

The primary endpoint measured will be safety of unilateral, 3Tesla, ExAblate Transcranial thalamotomy for TDPD as determined from adverse events recorded during the one year study period.

Secondary efficacy endpoints will include comparison of Baseline to Month 3 and Month 12 assessments for: 1)On-medication, tremor score from items 20 and 21 of the UPDRS. 2)On-medication, motor score from UPDRS, part III. 3)On-medication, total tremor (CRST) score. 4)Level of disability measured from Part C subsection of CRST. 5)Quality of life assessment with PDQ-39 and Quality of Life in Essential Tremor Questionnaire (QUEST) in this study.

+81-3-3265-4804

Nov. 26, 2018

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