UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	A Study to Evaluate the Effectiveness and Safety of ExAblate Transcranial MRgFUS Thalamotomy Treatment of Medication Refractory Essential Tremor Subjects
Title of the study (Brief title)	A Study to Evaluate the Effectiveness and Safety of ExAblate Transcranial MRgFUS Thalamotomy Treatment of Medication Refractory Essential Tremor Subjects
Region	Japan

Condition
Condition	Medication Refractory Essential Tremor
Classification by specialty	Neurology Neurosurgery
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	The objective of this prospective, multi-site, single-arm study is to test the efficacy of treatment using the ExAblate Transcranial System and to further demonstrate safety in medication-refractory tremor in subjects with essential tremor (ET).
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Pragmatic
Developmental phase	Phase III

Assessment
Primary outcomes	Safety: To evaluate the incidence and severity of adverse events (AE/AEs) associated with ExAblate Transcranial MRgFUS treatment of medication-refractory ET Effectiveness: To determine the effectiveness of the ExAblate Transcranial MRgFUS treatment of medication-refractory tremor (i.e. ET). Efficacy will be determined utilizing the Clinical Rating Scale for Tremor (CRST) in ET from examinations at baseline and 3-Months post-ExAblate treatment.
Key secondary outcomes

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Self control
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Device,equipment
Interventions/Control_1	The objective of this prospective, single-arm study is to test the efficacy of treatment using the ExAblate Transcranial System and to further demonstrate safety in medication-refractory tremor in subjects with essential tremor (ET).
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	22 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	1. Men and women age 22 years or older 2. Subjects who are able and willing to give consent and able to attend all study visits, 3. A diagnosis of ET as confirmed from clinical history and examination by a neurologist or neurosurgeon specialized in movement disorder 4. Have had an inadequate response to one or two oral doses of medication, per local standards. An inadequate medication trial is defined as a therapeutic dose of each medication and poor response to drug, or the development of side effects as the medication dose is titrated. 5. Following the 1-month medication stability period, subject must be on stable medication for tremor a. The 1-Month stability period visit will be 1-month post consent date 6. Subjects on stable antidepressant medications for at least 3 months may be enrolled into this study (i.e., no change in medication drug or dosage for 3 months). 7. Vim nucleus of thalamus can be target by the ExAblate device. The thalamic region must be apparent on MRI such that targeting can be performed by measurement from a line connecting the anterior and posterior commissures of the brain. 8. Able to communicate sensations during the ExAblate TcMRgFUS treatment 9. Postural or intention tremor severity score of greater than or equal to 2 in the dominant hand/arm as measured by the CRST rating scale while stable on medication. 10. May have bilateral appendicular tremor 11. Significant disability due to essential 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]) 12. Inclusion and exclusion criteria have been agreed upon by two members of the medical team.
Key exclusion criteria	1. Subjects with unstable cardiac status 2. Subjects exhibiting any behaviors consistent with ethanol or substance abuse 3. Severe hypertension 4. Subjects with standard contraindications for MR imaging. 5. Known intolerance or allergies to the MRI contrast agent. 6. Patient with severely impaired renal function or who is on dialysis 7. History of abnormal bleeding or coagulopathy. 8. Receiving anticoagulant or antiplatelet therapy within one week, or drugs 9. Active or suspected acute or chronic uncontrolled infection 10. History of immunocompromise. 11. History of intracranial hemorrhage 12. Cerebrovascular disease 13. Subjects with uncontrolled symptoms and signs of increased intracranial pressure. 14. Individuals who are not able or willing to tolerate the required prolonged stationary supine position. 15. Are participating or have participated in another clinical trial 16. Significant claustrophobia 17. Subjects unable to communicate. 18. Presence of any other neurodegenerative disease such as Parkinson plus syndromes 19. Anyone suspected to have the diagnosis of idiopathic Parkinson's disease. 20. Presence of significant cognitive impairment 21. Subjects with life threatening systemic disease 22. Subjects with a history of seizures 23. Subjects with presence or history of psychosis or active mood disorders will be excluded. 24. Subjects with risk factors for intraoperative or postoperative bleeding. 25. Subjects with brain tumors 26. Pregnancy or lactation. 27. Legal incapacity or limited legal capacity. 28. Subjects who have had deep brain stimulation or a prior stereotactic ablation of the basal ganglia 29. Subjects who have been administered botulinum toxins 30. Subjects who have an Overall Skull Density Ratio of 0.3 or less as calculated from the screening CT. 31. Any illness that in the investigator's opinion preclude participation in this study.
Target sample size	10

Research contact person
Name of lead principal investigator	Haruhiko Kishima
Organization	Osaka University School of Medicine
Division name	Department of Neurosurgery
Address	2-2 Yamadaoka,Suita,Osaka 565-0871,Japan
TEL	06-6879-3652
Email	yoshimine@nsurg.med.osaka-u.ac.jp

Public contact
Name of contact person	Satoru Oshino
Organization	Osaka University School of Medicine
Division name	Department of Neurosurgery
Address	2-2 Yamadaoka,Suita,Osaka 565-0871,Japan
TEL	06-6879-3652
Homepage URL
Email	hkishima@nsurg.med.osaka-u.ac.jp

Sponsor
Institute	Department of Neurosurgery, Osaka University School of Medicine
Institute
Department

Funding Source
Organization	InSightec Japan
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	大阪大学医学部付属病院（大阪府）、彩都友紘会病院（大阪府）

Other administrative information
Date of disclosure of the study information	2015 Year 10 Month 27 Day

Progress
Recruitment status	Main results already published
Date of protocol fixation	2015 Year 06 Month 29 Day
Anticipated trial start date	2015 Year 10 Month 30 Day
Last follow-up date	2017 Year 03 Month 31 Day
Date of closure to data entry	2017 Year 08 Month 31 Day
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2015 Year 10 Month 26 Day
Last modified on	2018 Year 05 Month 11 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000021781