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

NCT06584383 | Active Not Recruiting

• 1 other identifier: PD017
• Study Type: interventional
• Target: 67
• Locations: 3 countries
• Sites: 4

Brief Summary

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.

Conditions

Parkinson Disease

Keywords

Exablate; MRgFUS; Subthalamotomy

Outcome Measures

Primary Outcomes (1)

• MDS-UPDRS Part III OFF Medication

  Between-group difference (Exablate and control) in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III at 12 months in the off-medication state.

  12 Months

Secondary Outcomes (9)

• PD-specific spatial covariance patterns (PDRP or PD related metabolic pattern) with brain 18F-fluorodeoxyglucose- Positron emission tomography

  12 Months

• MDS-UPDRS III OFF-med video-based evaluation

  12 Months

• MDS-UPDRS I, II, III (ON and OFF meds) and UPDRS IV

  12 Months, 24 Months, 36 Months

• MDS Unified Dyskinesia Rating Scale

  12 Months, 24 Months, 36 Months

• Quality of life assessment (PDQ39)

  12 Months, 24 Months, 36 Months

Other Outcomes (3)

• Safety: Incidence and frequency of adverse events related to the treatment.

  36 Months

• Exploratory assessment: F- Dopa PET assessment

  12 Months, 36 Months

• Exploratory assessment: Time to Parkinson's Disease Progression

  12 Months, 24 Months, 36 Months

Study Arms (3)

Exablate Arm

EXPERIMENTAL

Subjects will receive Exablate MRgFUS subthalamotomy

Procedure: Exablate MRgFUS subthalamotomy

Control Arm

ACTIVE COMPARATOR

Subjects will receive best medical treatment. If patients from the control arm undergo the unilateral Exablate MRgFUS subthalamotomy between month 12 to 36, they will be exiting the study.

Procedure: Exablate MRgFUS subthalamotomy; Drug: Best Medical Treatment

Reference Arm

ACTIVE COMPARATOR

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.

Drug: Best Medical Treatment

Interventions

Exablate MRgFUS subthalamotomy PROCEDURE

Exablate MRgFUS subthalamotomy for Parkinson's Disease

Control Arm; Exablate Arm

Best Medical Treatment DRUG

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

Control Arm; Reference Arm

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• InSightec: lead

Study Sites (4)

Pontificia Universidad Catolica de Chile

Santiago, Chile

Location

Universitätsklinikum Schleswig-Holstein, Campus Kiel (UKSH)

Kiel, 24105, Germany

Location

HM CINAC- Hospital Universitario HM Puerta del Sur

Móstoles, 28938, Spain

Location

Clinica Universidad de Navarra

Pamplona, 31008, Spain

Location

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

• José Obeso, MD, PhD

  HM CINAC- Hospital Universitario HM Puerta del Sur

  PRINCIPAL INVESTIGATOR

• Raúl Martínez-Fernández, MD, PhD

  HM CINAC- Hospital Universitario HM Puerta del Sur

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: If patients from the control arm undergo the unilateral Exablate MRgFUS subthalamotomy between month 12 to 36, they will be exiting the study.

Study Record Dates

• First Submitted: August 30, 2024
• First Posted: September 4, 2024
• Study Start: August 1, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2029
• Last Updated: May 6, 2026

Record last verified: 2026-05

Locations

ES (2); DE (1); CL (1)