ExAblate Transcranial MRgFUS of the Globus Pallidum for Treatment of Parkinson's Disease

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

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02263885

Enrollment

Registered

2014-10-13

Start date

2015-04-30

Completion date

2019-07-26

Last updated

2022-01-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Parkinson's Disease

Keywords

Parkinson's Disease, ExAblate, MRgFUS

Brief summary

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 in subjects who are over 30 years of age and considered medication-refractory with advanced idiopathic Parkinson's disease (PD).

Detailed description

The purpose of this study is to evaluate the safety and initial clinical effectiveness of ExAblate Transcranial unilateral thermal ablation of the globus pallidus of subjects suffering from medication-refractory, advanced idiopathic PD. Data will be collected to establish the basic safety and clinical efficacy of this type of treatment as the basis for later studies that will evaluate the full clinical efficacy.

Interventions

DEVICEExAblate Transcranial System

Transcranial MRgFUS

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

30 Years to No maximum

Healthy volunteers

Inclusion criteria

* Men and women, age 30 years and older * Subjects who are able and willing to give informed consent and able to attend all study visits through 24 Months * Subjects with a diagnosis of idiopathic PD * Levodopa responsive as defined by at least a 30% reduction in MDS-UPDRS motor subscale in the ON vs OFF medication state. * Disabling motor complications of PD on optimum medical treatment * Predominant disability from one side of the body (i.e unilateral or markedly asymmetric disease) as determined by movement disorders neurologist and neurosurgeon * Subjects should be on a stable dose of all PD medications for 30 days prior to study entry. * Subject is able to communicate sensations during the ExAblate Transcranial procedure.

Exclusion criteria

* 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. * Any suspicion that Parkinsonian symptoms are a side effect from neuroleptic medications. * Subjects who have had deep brain stimulation or a prior stereotactic ablation of the basal ganglia * 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 * Subjects with significant depression as determined following a comprehensive assessment by a neuropsychologist. * Legal incapacity or limited legal capacity as determined by the neuropsychologist * Subjects exhibiting any behavior(s) consistent with ethanol or substance abuse * Subjects with unstable cardiac status including: 1. Unstable angina pectoris on medication 2. Subjects with documented myocardial infarction within six months of protocol entry 3. Significant congestive heart failure defined with ejection fraction \< 40 4. Subjects with unstable ventricular arrhythmias 5. Subjects with atrial arrhythmias that are not rate-controlled * Severe hypertension (diastolic BP \> 100 on medication) * Current medical condition resulting in abnormal bleeding and/or coagulopathy * 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 * 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 * 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; * Subjects with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices including cardiac pacemakers, size limitations, etc. * Significant claustrophobia that cannot be managed with mild medication. * Subjects who are not able or willing to tolerate the required prolonged stationary supine position during treatment. * History of intracranial hemorrhage * History of multiple strokes, or a stroke within past 6 months * Subjects with a history of seizures within the past year * Subjects with brain tumors * Subjects with intracranial aneurysms requiring treatment or arterial venous malformations (AVMs) requiring treatment. * Are participating or have participated in another clinical trial in the last 30 days * Any illness that in the investigator's opinion preclude participation in this study. * Subjects unable to communicate with the investigator and staff. * Pregnancy or lactation.

Design outcomes

Primary

Measure	Time frame	Description
Adverse Events	Month 24	The primary outcome of this feasibility trial was safety. Adverse Events were categorized by physicians as mild, moderate, or severe. Events resulting in impairment, requiring intervention to preclude impairment, or that were life threatening, and deaths were reported by physicians as Serious Adverse Events. Outcomes are entered in the adverse events module.

Secondary

Measure	Time frame	Description
Unified Dyskinesia Rating Scale Total Score.	Screening, Month 3, Month 6, Month 12, Month 24	The Unified Dyskinesia Rating Scale Total score assesses overall involuntary movements associated with the treatment of Parkinson's disease. The minimum score possible is 0. The maximum total score possible is 104. High scores show worse symptoms.
Unified Dyskinesia Rating Scale (UDysRS), Part III	Screening, Month 3, Month 6, Month 12, Month 24	The Unified Dyskinesia Ratient Scale (UDysRS) was developed to assess involuntary movements often associated with the treatment of Parkinson's disease. Part III evaluates the intensity of impairment of dyskinesia with respect to the performance of 7 tasks on a scale of 0 to 4. The sum of the Part III score ranges 0 to 28 and high scores show worse symptoms.
Movement Disorders Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Part III Motor Exam	Screening, Month 3, Month 6, Month 12, Month 24	The Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS UPDRSP Part III motor exam focuses specifically on the treated side tremor and motor fluctuations. Each of 11 items are scored from 0 to 4 for a total score minimum of 0 and a maximum of 44 points. High scores show worse symptoms.
Mood Disorders Society - Unified Parkinson's Disease Rating Scale Part II	Screening, Month 3, Month 6, Month 12, Month 24	.Part II of the Mood Disorders Society Unified Parkinson's Disease Rating Scale focuses on the impact of symptoms on motor aspects of daily living. Part II consists of 13 items scored from 0 to 4 for a maximum score of 52. High Part II scores indicate worse (greater) impact.
Mood Disorder Society Unified Parkinson's Disease Rating Scale Part IV	Screening, Month 3, Month 6, Month 12, Month 24	Part IV of the Mood Disorder Society Unified Parkinson's Disease Rating Scale assesses dyskinesias that include OFF-state dystonia; items include time spent with dyskinesia, functional impact of dyskinesia, time spent in the OFF state, functional impact of fluctuations, complexity of motor fluctuations and painful OFF state dystonia. Six items are scored 0 to 4 with a maximum total score of 24. High scores indicate worse symptoms.

Countries

United States

Participant flow

Participants by arm

Arm	Count
ExAblate Transcranial System Test Arm Transcranial ExAblate MRgFUS Transcranial MRgFUS lesioning of the Globus Pallidum	20
Total	20

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Alternative Treatment	3
Overall Study	Withdrawal by Subject	7

Baseline characteristics

Characteristic	ExAblate Transcranial System Test Arm
Age, Continuous	56.4 years STANDARD_DEVIATION 11.3
Race/Ethnicity, Customized Race Black	0 Participants
Race/Ethnicity, Customized Race Hispanic	2 Participants
Race/Ethnicity, Customized Race Other	0 Participants
Race/Ethnicity, Customized Race White	18 Participants
Region of Enrollment United States	20 participants
Sex: Female, Male Female	7 Participants
Sex: Female, Male Male	13 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 20
other Total, other adverse events	15 / 20
serious Total, serious adverse events	1 / 20

Outcome results

Primary

Adverse Events

The primary outcome of this feasibility trial was safety. Adverse Events were categorized by physicians as mild, moderate, or severe. Events resulting in impairment, requiring intervention to preclude impairment, or that were life threatening, and deaths were reported by physicians as Serious Adverse Events. Outcomes are entered in the adverse events module.

Time frame: Month 24

Arm	Measure	Value (NUMBER)
ExAblate Transcranial System Test Arm	Adverse Events	36 Number of Adverse Events

Secondary

Mood Disorder Society Unified Parkinson's Disease Rating Scale Part IV

Part IV of the Mood Disorder Society Unified Parkinson's Disease Rating Scale assesses dyskinesias that include OFF-state dystonia; items include time spent with dyskinesia, functional impact of dyskinesia, time spent in the OFF state, functional impact of fluctuations, complexity of motor fluctuations and painful OFF state dystonia. Six items are scored 0 to 4 with a maximum total score of 24. High scores indicate worse symptoms.