PD002J

JRCT ID: jRCTs032180186

Registered date:05/03/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Medically Refractory Dyskinesia Symptoms of Advanced Idiopathic Parkinsons Disease
• Date of first enrollment: 29/08/2017
• Target sample size: 10
• Study type: Interventional
• Intervention(s): The proposed study will evaluate the safety, and initial efficacy of using the ExAblate Transcranial to create a unilateral lesion in the globus pallidus as an adjunct to PD medications and considered medication refractory with advanced idiopathic Parkinsons disease.

Outcome(s)

• Primary Outcome: The proposed study will evaluate the safety, and initial efficacy of using the ExAblate Transcranial to create a unilateral lesion in the globus pallidus as an adjunct to PD medications.

Secondary Outcome

These secondary measures of safety will include evaluations post-treatment which are compared to a baseline assessment. These measures include;
MR imaging (1 day, 1 month).
Cognitive assessment by a neuropsychologist (6, 12 and 24 months) for comparison of clinically significant changes from baseline; CSSRS assessments at all visits.
Visual field testing (3 months).
Gait assessment(TGUG) at 1, 3, 6, 12 and 24 month.
Secondary efficacy endpoints will include comparison of Baseline to each follow-up visit assessment for;
Unified Dyskinesia Rating Scale .
Off-medication, motor score from the MDS-UPDRS, part III .
On-medication, motor score from MDS-UPDRS, part III and IV.
Clinician and Patient Global Impression of Change.
Patient Treatment Satisfaction.
Levodopa equivalent medication usage (milligrams).
Quality of life assessment with PDQ-39 .

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1.Men and women, age 20 years and older.
2.Subjects who are able and willing to give informed consent and able to attend all study visits through 24 Months.
3.Subjects with a diagnosis of idiopathic PD as confirmed by a movement disorder neurologist at the site.
4.Levodopa responsive as defined by at least a 30% reduction in MDS-UPDRS motor subscale in the ON vs OFF medication state.
5.MDS-UPDRS score of > 30 in the meds OFF condition.
6.Disabling motor complications of PD on optimum medical treatment characterized dyskinesia or motor fluctuations (MDS-UPDRS item 4.2 score of 2 or 3 in the meds ON condition).
7.Predominant disability from one side of the body.
8.Subjects should be on a stable dose of all PD medications for 30 days prior to study entry.
9.Subject is able to communicate sensations during the ExAblate Neuro procedure.

Exclude criteria

1.Hoehn and Yahr stage in the ON medication state of 3 or greater.
2.Presence of other central neurodegenerative disease suspected on neurological examination. These include: multisystem atrophy, progressive supranuclear palsy,
corticobasal syndrome, dementia with Lewy bodies, and Alzheimer's disease.
3.Any suspicion that Parkinsonian symptoms are a side effect from neuroleptic medications.
4.Subjects who have had deep brain stimulation or a prior stereotactic ablation of the basal ganglia.
5.Presence of significant cognitive impairment defined as score < 24 on the MMSE(Mini-Mental State Examination) or Mattis Dementia Rating Scale of 120 or lower.
6.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.
7.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.
8.Legal incapacity or limited legal capacity as determined by the neuropsychologist.
9.Subjects exhibiting any behavior(s) consistent with ethanol or substance abuse as defined by the criteria outlined 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).
10.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.
11.Severe hypertension (diastolic BP > 100 on medication) .
12.Current medical condition resulting in abnormal bleeding and/or coagulopathy.
13.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.
14.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 institution's laboratory standard.
15.Patient with severely impaired renal function with estimated glomerular filtration rate <30 mL/min/1.73m2 (or per local standards should that be more restrictive) and/or who is on dialysis.
16.Subjects with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices including cardiac pacemakers, size limitations, etc.
17.Significant claustrophobia that cannot be managed with mild medication.
18.Subject who weigh more than the upper weight limit of the MR scanner table and who cannot fit into the MR scanner.
19.Subjects who are not able or willing to tolerate the required prolonged stationary supine position during treatment.
20.History of intracranial hemorrhage.
21.History of multiple strokes, or a stroke within past 6 months.
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.Are participating or have participated in another clinical trial in the last 30 days.
26.Any illness that in the investigator's opinion preclude participation in this study.
27.Subjects unable to communicate with the investigator and staff.
28.Pregnancy or lactation.
29.All patients with severe premorbid risks [MDS-UPDRS Part II subsection activities of daily living scores of a three or four in question 2.1 (speech), question 2.2 (salivation), or question 2.3 (swallowing)] will be excluded.

Related Information

• Primary Sponsor: KAMEI TETSUMASA
• Source(s) of Monetary Support: InSightec
• Secondary ID(s): UMIN000033955