UMIN-CTR Clinical Trial

Public title

A Study to Evaluate the Effectiveness and Safety of ExAblate Transcranial MRgFUS
Thalamotomy Treatment of Medication
Refractory Essential Tremor Subjects

Acronym

Transcranial MRgFUS Thalamotomy on
Essential Tremor Subjects

Scientific Title

A Study to Evaluate the Effectiveness and Safety of ExAblate Transcranial MRgFUS
Thalamotomy Treatment of Medication
Refractory Essential Tremor Subjects

Scientific Title:Acronym

Transcranial MRgFUS Thalamotomy on
Essential Tremor Subjects

Region

Japan

Condition

Essential Tremor

Classification by specialty

Neurology

Neurosurgery

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

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 inpatients with essential tremor (ET).

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

1. Safety
Safety of ExAblate will be determined by an evaluation of the incidence and severity of device / treatment related complications from the first treatment day visit through ALL study follow ups. Adverse events (type, frequency, severity) are expected to be similar to those of previous studies using ExAblate TcMRgFUS for Thalamotomy.
All AEs will be reported and categorized by investigators as definitely, probably, possibly, or unrelated to the device or procedure and categorized by treatment group / treatment arm.

2. Effectiveness
Primary effectiveness will be evaluated using a validated, tremor rating scale: the Clinical Rating Scale for Tremors (CRST) for ET subjects, based upon subjects in whom unilateral ExAblate lesioning is attempted (i.e., Intent-to-Treat analysis).
Clinical assessments will be made at the following time points: screening, baseline with subjects on confirmed stable medication (at 1-months post screening), and post-treatment at 1 week, 1 month, 3 months, 6 months, and 12 months.

Key secondary outcomes

1. Quality life claims: Questionnaire for Essential Tremor (QUEST) outcome (upper extremity questions) at Months 3 change from Baseline

2. Durability (as measured by QUEST upper arm extremity questions) of the procedure as reflected by the efficacy data through change from baseline measures through Month 12 follow up

3. Subject daily functionalities: as measured by CRST Part-C (subscales) Month 12 as compared to Baseline

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Device,equipment

Maneuver

Interventions/Control_1

ExAblate MR Guided Focused Ultrasound is an attractive modality for non-invasive thermal ablation of soft tissue tumors [1-6]. Treatment begins by acquiring a series of MR images of the target tissue. The physician then reviews the images on the ExAblate system workstation, identifies a target volume on the MR images, delineates the treatment contours on the images, and reviews the treatment plan. Therapy planning software calculates the parameters required to effectively treat the defined region. During the treatment, an ultrasound transducer generates a point of focused ultrasound energy, called a sonication. The sonication raises the tissue temperature within a well-defined region, causing a thermal coagulation effect. MR images acquired during sonication provide a quantitative, real-time temperature map of the entire field-of-view around the target area to confirm the location of the sonication and the size of the coagulated region. The sonication process is repeated at multiple adjacent points to cover the entire prescribed treatment volume.

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

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. 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.
7. Able to communicate sensations during the ExAblate TcMRgFUS treatment
8. 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.
9. May have bilateral appendicular tremor
10. 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])
11. Inclusion and exclusion criteria have been agreed upon by two members of the medical team.
12. 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).

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 and/or who is on dialysis
7. History of abnormal bleeding and/or coagulopathy
8. Receiving anticoagulant or antiplatelet therapy within one week of focused ultrasound procedure or drugs known to increase risk or hemorrhage within one month of focused ultrasound procedure
9. Active or suspected acute or chronic uncontrolled infection
10. History of immunocompromise including those who are HIV positive
11. History of intracranial hemorrhage
12. Cerebrovascular disease
13. Subjects with uncontrolled symptoms and signs of increased intracranial pressure
14. Presence of any other neurodegenerative disease such as Parkinson-plus syndromes suspected on neurological examination
15. Anyone suspected to have the diagnosis of idiopathic Parkinson's disease
16. Presence of significant cognitive impairment
17. Subjects with life-threatening systemic disease
18. Subjects with a history of seizures within the past year
19. Subjects with presence or history of psychosis. Subjects with significant or active mood disorders including depression
20. Subjects with risk factors for intraoperative or postoperative bleeding
21. Subjects with brain tumors
22. Pregnancy or lactation
23. Subjects who have had deep brain stimulation or a prior stereotactic ablation of the basal ganglia
24. Subjects who have been administered botulinum toxins for 5 months prior to Baseline
25. Subjects who have an Overall Skull Density Ratio of 0.35 or less as calculated from the screening CT

Target sample size

10

Name of lead principal investigator

1st name
Middle name
Last name	Kazumichi Yamada

Organization

Kumamoto University Hospital

Division name

Division of Functional Neurosurgery

Zip code

Address

1-1-1, Honjo, Chuo-Ku, Kumamoto

TEL

096-373-5219

Email

yamadakazu@fc.kuh.kumamoto-u.ac.jp

Name of contact person

1st name
Middle name
Last name	Yu-ichi Tsutsumi

Organization

Hokuto Hospital

Division name

Employee Relations Division

Zip code

Address

7-5, Kisen, Inada-machi, Obihiro City, Hokkaido

TEL

0155488000

Homepage URL

http://www.hokuto7.or.jp/

Email

tsutsumi@hokuto7.or.jp

Institute

Departments of Neurology and Neurosurgery,
Hokuto Hospital

Institute

Department

Personal name

Organization

InSightec

Organization

Division

Category of Funding Organization

Outside Japan

Nationality of Funding Organization

Isurael

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2017

Year

01

Month

01

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

No longer recruiting

Date of protocol fixation

2015

Year

02

Month

09

Day

Date of IRB

Anticipated trial start date

2015

Year

03

Month

01

Day

Last follow-up date

2016

Year

12

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2016

Year

08

Month

16

Day

Last modified on

2016

Year

08

Month

16

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000027204