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A feasibility Clinical Trial of the Management of the Medically Refractory Dyskinesia Symptoms of Advanced Idiopathic Parkinson's Disease With Unilateral Lesioning of the Globus Pallidum Using the Exablate Transcranial System

PD002J (PD002J)

7

Demographic Variable:Men 0, Women 7 Average Age:Mean60.4, Standard Deviation 8.8

7 enrolled (5 complete/1 discontinued/1 excluded) See Appendix 2 for details

There were 24 cases of illness, etc. during the study period, of which 2 cases were serious adverse events, which were not caused by the implementation of the study.

<Primary endpoint> 1) MDS-UPDRS Part III(OFF) reactivity analysis and score reduction rate MDS-UPDRS Part III (when OFF) was evaluated for motor signs. The results are summarized in Tables 5 and 6 and FIG. Compared to baseline, scores improved by 42.6% at 1 month, 37.8% at 3 months, 30.4% at 6 months, 32.2% at 12 months, and 37.3% at 24 months. 2) MDS-UPDRS Part IV total score for each time of assessment of motor fluctuations on long-term treatment Table 7. and Figure 2 summarize the results regarding changes in symptoms after treatment procedures related to motor symptoms at MDS-UPDRS Part IV OFF. In this clinical study, when comparing the rate of change in scores for each evaluation point compared to screening, 37.2% after 1 month, 51.3% after 3 months, 45.2% after 6 months, and 53.3% after 12 months. , and 38.8% after 24 months. The improvement rate was highest 3 months after the treatment procedure. 3) MDS-UPDRS Part II Comprehensive score for each exercise evaluation in daily life Table 8 and Fig. 3 summarize the results of the MDS-UPDRS Part II total score at each evaluation time of exercise evaluation in daily life. Compared to the evaluation at screening, a decrease in score was confirmed until 3 months later, but an increase in score was confirmed after 3 months, indicating that the symptoms gradually returned. 4) Average total score for each time of evaluation for MDS-UPDRS The results are summarized in Table 9 and Figure 4 regarding the mean value of the total score for each evaluation time for MDS-UPDRS. No significant difference was observed in each of the five evaluation points. 5) Unified Dyskinesia Rating Scale (UDysRS) Total score for each evaluation Table 10 and Fig. 5 summarize the results of statistical analysis of the total score for each evaluation of the Unified Dyskinesia Rating Scale (UDysRS). Scores were significantly improved at 3 months (42.6%), 6 months (44.3%), and 12 months (46.1%) compared to screening. 6) Changes on the Global Impression Scale (CGI) and mean L-dopa dose Figures 6 and 7 summarize the changes on the Global Impression Scale and the mean dose of L-dopa. CGI was evaluated in seven stages. Both physician and subject evaluations were performed. Regarding the CGI of the subjects, satisfaction increased until 6 months after the treatment procedure, and the satisfaction after 6 months was the highest. In the case of evaluation by a doctor, scores were high at evaluation points after a long period of time from the treatment procedure, such as 6 months, 12 months, and 24 months. In addition, no significant change was observed in the mean L-dopa dose until the 24th month. 7) Evaluation of QOL by PDQ-39 We evaluated the QOL of the patient by PDQ-39 (The Parkinson's Disease Questionnaire), and figure 8 gathered it up in this in a statistical analysis level. There was little number of the items which adapted soon after the therapeutic procedure for 12 months for six months for three months, but the items which corresponded 24 months later increased when it was difficult that it handled difficulty, a necessary momentum to continue the kinesitherapy that will for the exercise with the limitation by the cost to feel the pressure that movement after, exercise had a problem on exercising lacked, and a momentum confirmed an item such as insufficient kinesitherapy feeling agony for the kinesitherapy that the will that exercised as pleasure not to function lacked. 8) Satisfaction rate of the subjects We heard a questionnaire than a patient and evaluated satisfaction about the treatment. And we summarized an analysis result in table 11. A therapeutic procedure was very high in satisfaction just after that, but it decreased and did the satisfaction with progress at the time from a therapeutic procedure. <Secondary endpoint> Occurrence of adverse events and serious adverse events. Adverse events and serious adverse events confirmed during clinical research are summarized in Tables 3 and 4. Eighteen mild (75.0%), two moderate (8.3%), and four severe (16.7%) adverse events were identified. In addition, two serious adverse events were confirmed, but both events were hospitalized for pain management and were discharged after the event disappeared or improved.

Some evaluations such as MDS-UPDRS Part III (OFF), MDS-UPDRS Part IV, and UDysRS showed improvement in symptoms, but in terms of exercise in daily life, the score was lower at 3 months after surgery compared to the evaluation at screening. Decrease, then increase was confirmed, and it was found that the symptoms gradually returned. There was no change in the average dose of L-dopa. Adverse events were confirmed as serious adverse events, but none were attributable to the conduct of the study.

Dec. 21, 2023

No

none

https://jrct.mhlw.go.jp/latest-detail/jRCTs032180306

Kimito Kondo

Hokuto hospital

7-5,Inadacho-kisen Obihiro-shi Hokkaido japan

cjkkondo@hokuto7.or.jp

Tamura Aiko

Hokuto hospital

7-5,Inadacho-kisen Obihiro-shi Hokkaido japan

+81-155-48-8000

crc@hokuto7.or.jp

Complete

April. 19, 2016

Interventional

single arm study

open(masking not used)

no treatment control/standard of care control

single assignment

treatment purpose

1.Men and woman,age 30 years and older.
2.Subjects who are able and willing to give informed consent and able to attend all study visits through 24 Month.
3.Subjects wtih a diagnosis of idiopathic PD by UK Brain Bank Criteria as confirmed by 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 OFFcondition
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 condion)
7.Predominant disability from one side of the body.
8.Subjects is able to communicate sensation during the ExAblate Neruo prosedure.
9.Subject is able to communicate sensations during the ExAblate Neuro procedure.

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,dementia with Lewy bodies,and Alzheimer's disease.
3.Any suspicion that Parkinsonian symptoms are a side effect from neuroleptic medication.
4.Subjects who have had deep brain stimulation or a prior stereotactic ablation of the basal ganglia.
5.Presence of significant cognitive imparrirment defined as score<21 on the Montreal Cognitive Assessment(MoCA)or Mattis Dementia Rating Scale of 120 or lower.
6.Unstable psychiatric desease,delusions,hallucinations,or suicidal ideation.Subjects with stable,chronic anxiety or depressive disorders may be included provided their medivcations have been stable for at least 60 days prior to study prior to study entry and if deemend appropriately managed bay the sited neuropyschologyst.
7.Subjects with significant depression as determined
following a comprehensiveassessment by a
neuropsychologist.Significant depression is being
defined quantitativelty asa a score of greater than 14
on the Beck Depression Inventory.
8.Legal incapacity or limited legal capacity as determined by the neuropsycholgist.
9.Subjects exhibiting any behavior(s) consistent with ethnol 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 12month 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
performancerelated to substance use;substance-related
absences,suspensions,or expulsions from school;or neblect of children or
household)
b.Recurrent substance use in situations in which it is physically hazardous
(such asdriving an automobile or operating a machine when impaored by
substance use)
c.Recurrent substance-related legal problems(such as arrests for substance
related disorderly conduct)
d.Continued substance use despite having 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.Subjacts with unstable ventricular arrhythmias
e.Subjects with atrial arrhythmias that are not rete-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 prosedure.
14.Subjects with risk factors for intraoperative or postoperative bleeding as indicated by : documented clinical coagulopathy,or INR coagulation studies ezceeding the institution's standard.
15.Patient with severely impaored renal function with estimated blomerular filtration rate < 30 ml/min/1.73m2 (or per local standaeds 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 incuding 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 who cannot fit into the MR scanner.
19.Subjects who are not able or willing totolerate the required prolonged stationary supine position during treatment.
20.History of intracranial hemorrhage
21.History of multiple strokes,or a stroke within past 6month.
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 clinicaltrial in the last 30 days.
26.Any illness that in the investigator's opinion preclude participation in this study.
27.Subject unable to communicate wtih the investigator and staff.
28.Pregnancy or lavtation.
29.All patients with sever premorbid risks (MDS-UPDRS Part2 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 exculded.

Both

Parkinson's Disease

MRguided focused ultrasound transcranial pallidotomy

To determine the level of effectiveness of the ExAblate Transcranial pallidotomy to manage the dyskinesia of subjects with medication-refractory, advanced
idiopathic PD.

To evaluate the incidence and severity of adverse events (AEs) associated with ExAblate Transcranial method of pallidotomy in subjects with medication-refractory,
advanced idiopathic PD.

+81-3-3265-4804

Feb. 14, 2019

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