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CompletedNCT03454425Updated Mar 24, 2026

A Study to Evaluate the Safety and Efficacy of ExAblate Subthalomotomy for the Treatment of Parkinson's Disease Motor Features

An interventional study of Exablate Subthalamotomy and Sham Exablate Subthalamotomy in Parkinson Disease, sponsored by InSightec. Completed at 1 site in Spain. Open to participants aged 30 Years and older. Per ClinicalTrials.gov, last updated 2026-03-24.

Sponsored by InSightec · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
36
Allocation
Randomized
Ages
30 Years and older
Sex
All
01

Study summary

The objective of this study is to test the efficacy and safety of unilateral subthalamotomy performed using the ExAblate System for the treatment of Parkinson's disease (PD) motor features.

Read the detailed description

A Prospective, Randomized, Sham Controlled Study to Evaluate the Safety and Efficacy of ExAblate Subthalomotomy for the treatment of Parkinson's disease motor features.

The objective of this prospective, randomized, double-blind (to subjects, examining neurologists and external video-based examination by Movement Disorders neurologist), two-arm study (ExAblate treated arm Vs ExAblate Sham treated control arm) is to confirm the efficacy of ExAblate Model 4000 Type 1 System for the treatment of Parkinson's disease (PD) motor features and to further demonstrate safety.

02

Conditions studied

  • Parkinson Disease

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Keywords

  • Parkinson's Disease
  • ExAblate
  • MRgFUS
  • Sub-Thalamotomy
03

Who can participate

Ages eligible
30 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Men and women age 30 years or older
  2. Subjects who are able and willing to give consent and able to attend all study visits.
  3. Subjects with a diagnosis of PD by UK Brain Bank Criteria as confirmed by a movement disorder neurologist at the site.
  4. Predominant motor features/disability from one side of the body (i.e asymmetry index > 1.5) as determined by a movement disorders neurologist.
  5. Motor clinical features non-optimally controlled by an adequate medical treatment prescription. An adequate medication prescription is defined as a therapeutic dose of each medication or the development of side effects as the medication dose is titrated.
  6. No major changes in pharmacological regime for PD should be done for the 30 days prior to procedure.
  7. Topographic coordinates of the subthalamic nucleus are localizable on MRI so that it can be targeted by the ExAblate device.
  8. Able to communicate sensations during the ExAblate MRgFUS treatment Inclusion and exclusion criteria have been agreed upon by two members of the medical team

Exclusion criteria

Exclusion Criteria:

  1. Hoehn and Yahr stage in the ON medication state of 2.5 or greater
  2. Presence of severe dyskinesia as noted by a score of 3 or 4 on questions 4.1 and 4.2 of the MDS-UPDRS.
  3. 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.
  4. Any suspicion that Parkinsonian symptoms are a side effect from neuroleptic medications.
  5. Subjects who have had deep brain stimulation or a prior stereotactic ablation of the basal ganglia
  6. Presence of significant cognitive impairment defined as score ≤ 21 on the Montreal Cognitive Assessment (MoCA) or Mattis Dementia Rating Scale of 120 or lower.
  7. 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
  8. 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.
  9. Legal incapacity or limited legal capacity as determined by the neuropsychologist
  10. 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
  11. Subjects with unstable cardiac status including
  12. Severe hypertension (diastolic BP > 100 on medication).
  13. History of or current medical condition resulting in abnormal bleeding and/or coagulopathy.
  14. 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
  15. 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
  16. 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;
  17. Subjects with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices including cardiac pacemakers, size limitations, etc.
  18. Significant claustrophobia that cannot be managed with mild medication.
  19. Subject who weight more than the upper weight limit of the MR table and who cannot fit into the MR scanner
  20. Subjects who are not able or willing to tolerate the required prolonged stationary supine position during treatment.
  21. History of intracranial hemorrhage
  22. History of multiple strokes, or a stroke within past 6 months
  23. Subjects with a history of seizures within the past year
  24. Subjects with malignant brain tumors
  25. Subjects with intracranial aneurysms requiring treatment or arterial venous malformations (AVMs) requiring treatment.
  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. Subjects who have an Overall Skull Density Ratio lower than 0.35 as calculated from the screening CT.
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Single (Outcomes assessor)
Enrollment
36 participants (actual)

Study arms

  • Experimental
    Exablate Subthalamotomy

    Exablate treatment for Parkinson's Disease Motor Features

    Device: Exablate Subthalamotomy

  • Sham comparator
    Sham ExAblate Subthalamotomy

    Device: Sham Exablate Subthalamotomy

Interventions

  • DeviceExablate Subthalamotomy

    ExAblate Subthalomotomy for the Treatment of Parkinson's Disease Motor Features

    Also known as: MRgFUS, Subthalamotomy

  • DeviceSham Exablate Subthalamotomy

    Sham ExAblate Subthalomotomy for the Treatment of Parkinson's Disease Motor Features

05

What researchers measure

Primary outcomes

  1. Efficacy - MDS-UPDRS

    between-group differences in the mean change (from baseline to 4 months) in the motor MDS-UPDRS score for the side contralateral to subthalamotomy (in the treated group) as compared with mean change in the MDS-UPDRS score for the side contralateral to the alleged subthalamotomy (in the sham-procedure group) in the off-medication condition

    Time frame: Baseline to 4 months post treatment

  2. Safety - Adverse Events

    To evaluate the incidence and severity of adverse events (AE/AEs) associated with ExAblate subthalamotomy for the treatment of PD motor features.

    Time frame: Baseline to 4 Months post treatment

Secondary outcomes

  1. MDS-UPDRS III ON-medication

    MDS-UPDRS III score in the contralateral body side ON-medication condition as measured by the BLINDED assessor

    Time frame: Baseline to Month 4 post treatment

  2. MDS-UPDRS III OFF-medication

    MDS-UPDRS III score in the contralateral body side OFF-medication condition as measured by the UNBLINDED assessor

    Time frame: Baseline to Month 4 post treatment

  3. MDS-UPDRS III- Contralateral ON-medication

    MDS-UPDRS III score in the contralateral body side ON-medication condition as measured by the UNBLINDED assessor

    Time frame: Baseline to Month 4 post treatment

  4. MDS-UPDRS III

    Specific PD motor features sub-scores (rigidity, bradykinesia, tremor) of MDS- UPDRS III in the contralateral body side by visit for the following: OFF and ON-medication condition as measured by the BLINDED assessor

    Time frame: Baseline to Month 4 post treatment

  5. MDS-UPDRS II

    Total score of MDS-UPDRS II

    Time frame: Baseline to Month 4 post treatment

  6. MDS-UPDRS III Blinded assessor

    Total score of MDS-UPDRS III as measured by the BLINDED assessor OFF- and ON-medication

    Time frame: Baseline to Month 4 post treatment

  7. MDS-UPDRS IV

    Total score of MDS-UPDRS IV and separated by each type of motor complication

    Time frame: Baseline to Month 4 post treatment

  8. PDG39

    Quality of life assessment with the PDQ39.

    Time frame: Baseline to Month 12 post treatment

  9. GIC

    Patient global impression of change from Baseline to Month 4 FU.

    Time frame: Baseline to Month 4 post treatment

  10. Levodopa

    Levodopa equivalent medication change usage (mg).

    Time frame: Baseline to Month 12 post treatment

  11. MDS-UPDRS

    Durability of the reduction in the contralateral motor MDS-UPDRS at 12 months in the treated group (measured only by the UNBLINDED assessor)

    Time frame: Baseline to Month 12 post treatment

  12. MDS-UPDRS

    Change in the total MDS-UPDRS III according to disease severity at baseline (as defined by the MDS-UPDRS III score).

    Time frame: Baseline to Month 12 post treatment

06

Study locations

1 site
  • Hospital Universitario HM Puerta Del Sur. CINAC
    Móstoles, Madrid 28938, Spain
07

References and documents

Publications

  • Martinez-Fernandez R, Natera-Villalba E, Manez Miro JU, Rodriguez-Rojas R, Marta Del Alamo M, Pineda-Pardo JA, Ammann C, Obeso I, Mata-Marin D, Hernandez-Fernandez F, Gasca-Salas C, Matarazzo M, Alonso-Frech F, Obeso JA. Prospective Long-term Follow-up of Focused Ultrasound Unilateral Subthalamotomy for Parkinson Disease. Neurology. 2023 Mar 28;100(13):e1395-e1405. doi: 10.1212/WNL.0000000000206771. Epub 2023 Jan 11. PubMed 36631272 ↗
  • Rodriguez-Rojas R, Pineda-Pardo JA, Manez-Miro J, Sanchez-Turel A, Martinez-Fernandez R, Del Alamo M, DeLong M, Obeso JA. Functional Topography of the Human Subthalamic Nucleus: Relevance for Subthalamotomy in Parkinson's Disease. Mov Disord. 2022 Feb;37(2):279-290. doi: 10.1002/mds.28862. Epub 2021 Dec 3. PubMed 34859498 ↗
  • Martinez-Fernandez R, Manez-Miro JU, Rodriguez-Rojas R, Del Alamo M, Shah BB, Hernandez-Fernandez F, Pineda-Pardo JA, Monje MHG, Fernandez-Rodriguez B, Sperling SA, Mata-Marin D, Guida P, Alonso-Frech F, Obeso I, Gasca-Salas C, Vela-Desojo L, Elias WJ, Obeso JA. Randomized Trial of Focused Ultrasound Subthalamotomy for Parkinson's Disease. N Engl J Med. 2020 Dec 24;383(26):2501-2513. doi: 10.1056/NEJMoa2016311. PubMed 33369354 ↗
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Registry details

Key details

Study ID
NCT03454425
Lead sponsor
InSightec
Responsible party
Sponsor
First posted
Mar 5, 2018
Start date
Feb 27, 2018
Primary completion
Jun 15, 2020
Completion
Jun 15, 2020
Last update
Mar 24, 2026

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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