Subthalamotomy by ExAblate Transcranial System to Treat Motor Features of Parkinson's Disease

NCT02912871 | Completed

• 1 other identifier: PD003E
• Study Type: interventional
• Target: 10
• Locations: 0 countries
• Sites: N/A

Brief Summary

Based on published animal and human studies, ExAblate Transcranial subthalamotomy can be as safe and as effective as any of the surgical treatments within the currently accepted standard of care including radiofrequency lesioning and Deep Brain Stimulation (DBS). A unilateral lesion of the subthalamic nucleus has shown reduction of contralateral motor symptoms in Parkinson's disease (PD). Using ExAblate Transcranial Magnetic Resonance guided High Intensity Focused Ultrasound (MRgHIFU) to create the subthalamotomy has several potential advantages over current therapies including the fact that transcranial lesioning can be performed in a precise manner with simultaneous as well as continuous clinical and radiographic monitoring. If the potential of ExAblate Transcranial subthalamotomy can be realized, it could supplant radiofrequency and radiosurgery techniques and provide a viable alternative procedure for subjects considering DBS.

Conditions

Parkinson's Disease

Keywords

subthalamotomy; motor features; deep brain stimulation

Outcome Measures

Primary Outcomes (2)

• All causes of morbidity

  Number of treatment-related adverse events as assessed by CTCAE v4.0

  within the first 6 months (plus minus 1 month) after treatment

• Efficacy

  Improvement in the score of the Movement Disorders Unified Parkinson's Disease Rating Scale III (MDS-UPDRS III) that evaluates motor features of PD. The scale will be assessed pretreatment and after intervention and the reduction after treatment in the total MDS-UPDRS III score and the score in the treated hemibody will be measured. MDS-UPDRS III is a scale that assesses all the motor features of PD (akinesia, tremor, rigidity, gait disturbance). Score range between 0 (no presence of motor features) and 132 (maximum score for all items).

  6 months

Secondary Outcomes (7)

• MDS-UPDRS I

  6 months

• MDS-UPDRS II

  6 months

• MDS-UPDRS IV

  6 months

• Dyskinesia severity as assessed through the Dyskinesia rating scale

  6 months

• Levodopa equivalent medication usage (milligrams) when applicable

  6 months

Study Arms (1)

MRIgHIFU unilateral subthalamotomy

EXPERIMENTAL

Unilateral Subthalamotomy performed by MRI guided High intensity focused ultrasound in a single session.

Other: MRIgHIFU unilateral subthalamotomy

Interventions

MRIgHIFU unilateral subthalamotomy OTHER

High Intensity focused ultrasound unilateral subthalamotomy: Unilateral thermolesion in the Subthalamic nucleus performed by High Intensity Focused ultrasound

MRIgHIFU unilateral subthalamotomy

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 6 Months
• Subjects with a diagnosis of PD by United Kingdom Brain Bank Criteria as confirmed by a movement disorder neurologist at the site
• Predominant disability from one side of the body (i.e unilateral or markedly asymmetric disease) as determined by a movement disorders neurologist
• Subjects should be on a stable dose of all PD medications for 30 days prior to study entry, if possible.
• Topographic coordinates of the subthalamic nucleus are localizable on Magnetic resonance imaging (MRI) so that it can be targeted by the ExAblate device.
• Subject is able to communicate sensations during the ExAblate Transcranial procedure.

You may not qualify if:

• Hoehn and Yahr stage in the ON medication state of 2.5 or greater
• Presence of severe dyskinesia as noted by a score of 3 or 4 on questions 4.1 and 4.2 of the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS).
• 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
• Presence of significant cognitive impairment defined as score ≤ 21 on the Montreal Cognitive Assessment (MoCA) or Mattis Dementia Rating Scale of 120 or lower.
• 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. 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 Diagnostic and Statistical Manual of Mental Disorders-IV (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:

Sponsors & Collaborators

• Fundación de investigación HM: lead
• Insightech: collaborator

Related Publications (6)

• Elias WJ, Huss D, Voss T, Loomba J, Khaled M, Zadicario E, Frysinger RC, Sperling SA, Wylie S, Monteith SJ, Druzgal J, Shah BB, Harrison M, Wintermark M. A pilot study of focused ultrasound thalamotomy for essential tremor. N Engl J Med. 2013 Aug 15;369(7):640-8. doi: 10.1056/NEJMoa1300962.

  PMID: 23944301 BACKGROUND

• Lipsman N, Schwartz ML, Huang Y, Lee L, Sankar T, Chapman M, Hynynen K, Lozano AM. MR-guided focused ultrasound thalamotomy for essential tremor: a proof-of-concept study. Lancet Neurol. 2013 May;12(5):462-8. doi: 10.1016/S1474-4422(13)70048-6. Epub 2013 Mar 21.

  PMID: 23523144 BACKGROUND

• Alvarez L, Macias R, Pavon N, Lopez G, Rodriguez-Oroz MC, Rodriguez R, Alvarez M, Pedroso I, Teijeiro J, Fernandez R, Casabona E, Salazar S, Maragoto C, Carballo M, Garcia I, Guridi J, Juncos JL, DeLong MR, Obeso JA. Therapeutic efficacy of unilateral subthalamotomy in Parkinson's disease: results in 89 patients followed for up to 36 months. J Neurol Neurosurg Psychiatry. 2009 Sep;80(9):979-85. doi: 10.1136/jnnp.2008.154948. Epub 2009 Feb 9.

  PMID: 19204026 BACKGROUND

• 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.

  PMID: 36631272 DERIVED

• 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.

  PMID: 34859498 DERIVED

• Martinez-Fernandez R, Rodriguez-Rojas R, Del Alamo M, Hernandez-Fernandez F, Pineda-Pardo JA, Dileone M, Alonso-Frech F, Foffani G, Obeso I, Gasca-Salas C, de Luis-Pastor E, Vela L, Obeso JA. Focused ultrasound subthalamotomy in patients with asymmetric Parkinson's disease: a pilot study. Lancet Neurol. 2018 Jan;17(1):54-63. doi: 10.1016/S1474-4422(17)30403-9. Epub 2017 Dec 5.

  PMID: 29203153 DERIVED

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

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

Study Officials

• Jose Obeso, MD, PhD

  CINAC, HM Puerta del Sur. Avda. Carlos V nº 70. CP 28938. Móstoles MADRID (SPAIN) Tel: +34 91 2673201; Email: consulta.hmcinac@hmhospitales.com

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2016
• First Posted: September 23, 2016
• Study Start: April 1, 2016
• Primary Completion: January 1, 2017
• Study Completion: January 1, 2017
• Last Updated: January 31, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share