| Field | Value | |-------|-------| | NCT Number | NCT06584383 | | Title | MR-Guided Focused Ultrasound Unilateral Subthalamotomy for Early-Stage Parkinson's Disease | | Status | Recruiting | | Phase | Phase 2 | | Condition(s) | Parkinson's Disease (early-stage, Hoehn & Yahr 1-2) | | Intervention | Exablate MR-guided Focused Ultrasound (MRgFUS) unilateral subthalamotomy | | Comparator | Best Medical Treatment (BMT) | | Sponsor | InSightec Ltd. | | Locations | Multiple international centers |
Study Description
This Phase 2 clinical trial evaluates the safety and efficacy of MR-guided focused ultrasound (MRgFUS) unilateral subthalamotomy compared to best medical treatment in patients with early-stage Parkinson's disease. The study targets individuals with Hoehn & Yahr stages 1-2 who have asymmetric motor symptoms predominant on one side of the body.
Rationale for Early Intervention
The rationale for performing subthalamotomy in early-stage PD differs from the established use of deep brain stimulation (DBS) in advanced PD:
| Field | Value | |-------|-------| | NCT Number | NCT06584383 | | Title | MR-Guided Focused Ultrasound Unilateral Subthalamotomy for Early-Stage Parkinson's Disease | | Status | Recruiting | | Phase | Phase 2 | | Condition(s) | Parkinson's Disease (early-stage, Hoehn & Yahr 1-2) | | Intervention | Exablate MR-guided Focused Ultrasound (MRgFUS) unilateral subthalamotomy | | Comparator | Best Medical Treatment (BMT) | | Sponsor | InSightec Ltd. | | Locations | Multiple international centers |
Study Description
This Phase 2 clinical trial evaluates the safety and efficacy of MR-guided focused ultrasound (MRgFUS) unilateral subthalamotomy compared to best medical treatment in patients with early-stage Parkinson's disease. The study targets individuals with Hoehn & Yahr stages 1-2 who have asymmetric motor symptoms predominant on one side of the body.
Rationale for Early Intervention
The rationale for performing subthalamotomy in early-stage PD differs from the established use of deep brain stimulation (DBS) in advanced PD:
Neuroprotection Hypothesis: Earlier intervention may preserve dopaminergic neurons by reducing excessive excitatory drive from the subthalamic nucleus (STN)[@stn_anatomy_2024]
Motor Complication Prevention: May reduce the development of levodopa-induced dyskinesas
Quality of Life: Early motor symptom control may improve functional independence
Disease Modification Evidence: STN is a key component of basal ganglia circuitry that becomes hyperactive in PD
Why Subthalamotomy?
The subthalamic nucleus (STN) plays a critical role in the basal ganglia motor circuit:
Normal Function: STN provides excitatory (glutamatergic) input to the internal globus pallidus (GPi) and substantia nigra pars reticulata (SNr)
PD Pathology: In Parkinson's disease, reduced dopamine leads to excessive STN output, causing:
Increased GPi/SNr activity
Reduced thalamic facilitation
Motor slowing and rigidity
Targeting the STN with focal lesioning or stimulation can reduce this hyperactivity and improve motor symptoms.
Mechanism of Action
MR-Guided Focused Ultrasound (MRgFUS)
The ExAblate Neuro system uses focused acoustic energy to create a thermal lesion:
Mermaid diagram (expand to render)
Procedure Steps
Pre-Procedure Planning
High-resolution MRI for STN targeting
Skull bone density assessment
Confirmation of unilateral symptoms
Treatment Session
Patient positioned in MR gantry
Stereotactic frame applied
Low-power sonication for targeting verification
High-power sonication for lesion creation
Real-Time Monitoring
Temperature mapping by MRI
Continuous neurological monitoring
Adjustments as needed
Post-Procedure
MRI to confirm lesion
Neurological assessment
Follow-up imaging
Physiological Effects
| Effect | Mechanism | |--------|-----------| | Reduced STN activity | Thermal lesion destroys hyperactive neurons | | Decreased GPi inhibition | Normalizes output to thalamus | | Improved motor function | Enhanced thalamocortical facilitation | | Contralateral improvement | STN lesion effects on opposite side |
Pregnancy: Female patients of childbearing potential
Implants: Contraindicated ferromagnetic devices
Outcome Measures
Primary Outcomes
| Measure | Timepoint | Description | |---------|----------|------------| | Motor Function | 12 months | Change in MDS-UPDRS Part III "OFF" medication score | | Adverse Events | Throughout | Incidence of serious adverse events related to procedure |