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

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

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

Region

Japan

Condition

Medication Refractory Essential Tremor

Classification by specialty

Neurology

Neurosurgery

Classification by malignancy

Others

Genomic information

NO

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

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

Study type

Interventional

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

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

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

Name of lead principal investigator

1st name
Middle name
Last name	Haruhiko Kishima

Organization

Osaka University School of Medicine

Division name

Department of Neurosurgery

Zip code

Address

2-2 Yamadaoka,Suita,Osaka 565-0871,Japan

TEL

06-6879-3652

Email

yoshimine@nsurg.med.osaka-u.ac.jp

Name of contact person

1st name
Middle name
Last name	Satoru Oshino

Organization

Osaka University School of Medicine

Division name

Department of Neurosurgery

Zip code

Address

2-2 Yamadaoka,Suita,Osaka 565-0871,Japan

TEL

06-6879-3652

Homepage URL

Email

hkishima@nsurg.med.osaka-u.ac.jp

Institute

Department of Neurosurgery, Osaka University School of Medicine

Institute

Department

Personal name

Organization

InSightec Japan

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

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

大阪大学医学部付属病院（大阪府）、彩都友紘会病院（大阪府）

Date of disclosure of the study information

2015

Year

10

Month

27

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

Main results already published

Date of protocol fixation

2015

Year

06

Month

29

Day

Date of IRB

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

Other related information

Registered date

2015

Year

10

Month

26

Day

Last modified on

2018

Year

05

Month

11

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000021781