A Prospective, Randomized, Controlled Trial to Test Safety and Effectiveness of Unilateral Exablate MR-guided Focused Ultrasound Subthalamotomy in Patients With Early-Stage Parkinson's Disease

NCT ID: NCT06584383

Last Updated: 2026-01-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

72 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-08-01

Study Completion Date

2029-09-30

Brief Summary

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This prospective, randomized, multicenter study aims to evaluate in Early-Stage Parkinson's Disease (ESPD) patients the safety and effectiveness of treatment with Exablate MRgFUS subthalamotomy vs best medical treatment.

Detailed Description

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This is a prospective, randomized (ratio 2:1), multicenter study to evaluate in Early-Stage Parkinson's Disease (ESPD) patients the safety and effectiveness of treatment with Exablate MRgFUS subthalamotomy vs best medical treatment. Patients assigned to the treatment arm will receive unilateral Exablate MRgFUS subthalamotomy. Patients assigned to control group will receive best medical treatment.

Conditions

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Parkinson Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

It is contemplated that, if the patients from the control arm require unilateral Exablate MRgFUS subthalamotomy, the treatment could be performed after Month 12 visit.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Exablate Arm

Subjects will receive Exablate MRgFUS subthalamotomy

Group Type EXPERIMENTAL

Exablate MRgFUS subthalamotomy

Intervention Type PROCEDURE

Exablate MRgFUS subthalamotomy for Parkinson's Disease

Control Arm

Subjects will receive best medical treatment. It is contemplated that, if the patients from the control arm require unilateral Exablate MRgFUS subthalamotomy, the treatment could be performed after Month 12 visit.

Group Type ACTIVE_COMPARATOR

Exablate MRgFUS subthalamotomy

Intervention Type PROCEDURE

Exablate MRgFUS subthalamotomy for Parkinson's Disease

Best Medical Treatment

Intervention Type DRUG

Subjects will be managed according to conventional therapeutic guidelines (i.e., best medical treatment) for Parkinson's Disease

Reference Arm

Patients fulfilling all inclusion/exclusion criteria except for the SDR requirements (and so anatomically not able to undergo MRgFUS subthalamotomy) will be offered the option to receive best medical treatment and will be formally followed as a reference comparator for up to 3 years.

Group Type ACTIVE_COMPARATOR

Best Medical Treatment

Intervention Type DRUG

Subjects will be managed according to conventional therapeutic guidelines (i.e., best medical treatment) for Parkinson's Disease

Interventions

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Exablate MRgFUS subthalamotomy

Exablate MRgFUS subthalamotomy for Parkinson's Disease

Intervention Type PROCEDURE

Best Medical Treatment

Subjects will be managed according to conventional therapeutic guidelines (i.e., best medical treatment) for Parkinson's Disease

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Men and women; age 30 to 65 years old
* Subjects who are able and willing to give consent and able to attend all study visits. - Subjects with a diagnosis of PD according to the modified clinical criteria by the Movement Disorders Society, for less than 5 years and more than 12 months.
* Off-medication MDS-UPDRS part III of the most affected body side ≥ 10
* Motor signs predominantly present in one body side: Asymmetry index (MDS-UPDRS III of the most affected side/MDS-UPDRS III of the least effected side) ≥ 2.
* Patients should have a stable pharmacological regime for the last 4-weeks prior to baseline evaluation.
* Topographic coordinates of the subthalamic nucleus are localizable on MRI so that it can be targeted by the Exablate device.
* Skull density ratio (SDR) score of 0.40 or higher\*. The SDR is a determinant factor for the suitability to MRgFUS ablation. SDR is a ratio of ultrasound energy penetration through the skull. The SDR threshold for using Exablate 4000 is established at 0.4 with patients having SDR below that value considered unsuitable candidates.
* Able to communicate sensations during the Exablate MRgFUS treatment.

Exclusion Criteria

* MDS-UPDRS part III OFF medications \> 32 in the off state and/or Hoehn and Yahr state ON medication greater than 2.
* Significative evidence (by clinical history) of having developed features indicative of PD motor onset 2 or more years prior to formal diagnosis.
* Presence of clinically relevant levodopa-induced dyskinesia and/or motor fluctuations as noted by a score \> 1 on questions 4.2 or 4.4 of the MDS-UPDRS, that assess disability resulting from motor complications.
* Levodopa daily dose higher than 500mg or 750 levodopa-equivalents daily.
* Presence of any symptoms or signs suggesting other central neurodegenerative disease such as multisystem atrophy, progressive supranuclear palsy, cortico-basal syndrome, dementia with Lewy bodies, and Alzheimer's disease.
* Any suspicion that parkinsonian symptoms are a side effect attributable to intake of neuroleptic or other medications.
* Subjects who have had deep brain stimulation or a prior stereotactic ablation for the treatment of movement disorders.
* Presence of significant cognitive impairment measured by standard of care method at the center.
* Patients with clinically relevant co-morbidity such as severe hypertension, diabetes, cardiac, metabolic, and psychiatric conditions
* 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.
* Legal incapacity or limited legal capacity as determined by the neuropsychologist.
* 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:

* 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).
* 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).
* Recurrent substance-related legal problems (such as arrests for substance related disorderly conduct).
* 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).
* Subjects with unstable cardiac status including:

* Unstable angina pectoris on medication
* Subjects with documented myocardial infarction within six months of protocol entry
* Significant congestive heart failure defined with ejection fraction \<40.
* Subjects with unstable ventricular arrhythmias
* Subjects with atrial arrhythmias that are not rate controlled.
* Severe hypertension (diastolic BP \>100 on medication).
* History of or 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 \<30mL/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.
* Subject who weighs more than the upper weight limit of the MR table and who cannot fit into the MR scanner.
* 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 malignant brain tumors.
* Subjects with intracranial aneurysms requiring treatment or arterial venous malformations (AVMs) requiring treatment.
* 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.
* Patients without clinically relevant parkinsonism in the off- state as evaluated by two examining neurologists (or MDS- UPDRS III in the most affected side \<10).
Minimum Eligible Age

30 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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InSightec

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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José Obeso, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

HM CINAC- Hospital Universitario HM Puerta del Sur

Raúl Martínez-Fernández, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

HM CINAC- Hospital Universitario HM Puerta del Sur

Locations

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Pontificia Universidad Catolica de Chile

Santiago, , Chile

Site Status RECRUITING

Universitätsklinikum Schleswig-Holstein, Campus Kiel (UKSH)

Kiel, , Germany

Site Status RECRUITING

HM CINAC- Hospital Universitario HM Puerta del Sur

Móstoles, , Spain

Site Status RECRUITING

Clinica Universidad de Navarra

Pamplona, , Spain

Site Status RECRUITING

Countries

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Chile Germany Spain

Central Contacts

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Pascalle Reiters

Role: CONTACT

+31-6-53726776

Elisa Cerutti

Role: CONTACT

+39 3459182413

Facility Contacts

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Carlos Juri

Role: primary

Steffen Paschen

Role: primary

José Obeso

Role: primary

Raúl Martínez-Fernández

Role: backup

Maria Cruz Rodriguez Oroz

Role: primary

Other Identifiers

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PD017

Identifier Type: -

Identifier Source: org_study_id

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