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

• ClinicalTrials.gov Identifier: NCT03454425
• Recruitment Status: Active, not recruiting
• First Posted: March 5, 2018
• Last Update Posted: August 3, 2022
• Sponsor: InSightec
• Information provided by (Responsible Party): InSightec

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Parkinson Disease	Device: Exablate Subthalamotomy; Device: Sham Exablate Subthalamotomy	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Prospective, Randomized, Sham Controlled Study to Evaluate the Safety and Efficacy of ExAblate Subthalomotomy for the Treatment of Parkinson's Disease Motor Features
• Actual Study Start Date: February 27, 2018
• Estimated Primary Completion Date: January 30, 2023
• Estimated Study Completion Date: March 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Exablate Subthalamotomy; Exablate treatment for Parkinson's Disease Motor Features	Device: Exablate Subthalamotomy; ExAblate Subthalomotomy for the Treatment of Parkinson's Disease Motor Features; Other Names: MRgFUS; Subthalamotomy
Sham Comparator: Sham ExAblate Subthalamotomy	Device: Sham Exablate Subthalamotomy; Sham ExAblate Subthalomotomy for the Treatment of Parkinson's Disease Motor Features

Outcome Measures

Primary Outcome Measures :

1. Efficacy - MDS-UPDRS [ Time Frame: Baseline to 4 months post treatment ]
   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
2. Safety - Adverse Events [ Time Frame: Baseline to 4 Months post treatment ]
   To evaluate the incidence and severity of adverse events (AE/AEs) associated with ExAblate subthalamotomy for the treatment of PD motor features.

Secondary Outcome Measures :

1. MDS-UPDRS III ON-medication [ Time Frame: Baseline to Month 4 post treatment ]
   MDS-UPDRS III score in the contralateral body side ON-medication condition as measured by the BLINDED assessor
2. MDS-UPDRS III OFF-medication [ Time Frame: Baseline to Month 4 post treatment ]
   MDS-UPDRS III score in the contralateral body side OFF-medication condition as measured by the UNBLINDED assessor
3. MDS-UPDRS III- Contralateral ON-medication [ Time Frame: Baseline to Month 4 post treatment ]
   MDS-UPDRS III score in the contralateral body side ON-medication condition as measured by the UNBLINDED assessor
4. MDS-UPDRS III [ Time Frame: Baseline to Month 4 post treatment ]
   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
5. MDS-UPDRS II [ Time Frame: Baseline to Month 4 post treatment ]
   Total score of MDS-UPDRS II
6. MDS-UPDRS III Blinded assessor [ Time Frame: Baseline to Month 4 post treatment ]
   Total score of MDS-UPDRS III as measured by the BLINDED assessor OFF- and ON-medication
7. MDS-UPDRS IV [ Time Frame: Baseline to Month 4 post treatment ]
   Total score of MDS-UPDRS IV and separated by each type of motor complication
8. PDG39 [ Time Frame: Baseline to Month 12 post treatment ]
   Quality of life assessment with the PDQ39.
9. GIC [ Time Frame: Baseline to Month 4 post treatment ]
   Patient global impression of change from Baseline to Month 4 FU.
10. Levodopa [ Time Frame: Baseline to Month 12 post treatment ]
    Levodopa equivalent medication change usage (mg).
11. MDS-UPDRS [ Time Frame: Baseline to Month 12 post treatment ]
    Durability of the reduction in the contralateral motor MDS-UPDRS at 12 months in the treated group (measured only by the UNBLINDED assessor)
12. MDS-UPDRS [ Time Frame: Baseline to Month 12 post treatment ]
    Change in the total MDS-UPDRS III according to disease severity at baseline (as defined by the MDS-UPDRS III score).

Eligibility Criteria

• Ages Eligible for Study: 30 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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:

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.

Contacts and Locations

Locations

Spain

Hospital Universitario HM Puerta Del Sur. CINAC

Móstoles, Madrid, Spain, 28938

Sponsors and Collaborators

InSightec

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

• Responsible Party: InSightec
• ClinicalTrials.gov Identifier: NCT03454425
• Other Study ID Numbers: PD010
• First Posted: March 5, 2018
• Last Update Posted: August 3, 2022
• Last Verified: August 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by InSightec:

Parkinson's Disease; ExAblate; MRgFUS; Sub-Thalamotomy

Additional relevant MeSH terms:

Parkinson Disease; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases