| 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 |
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.
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
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.
The ExAblate Neuro system uses focused acoustic energy to create a thermal lesion:
flowchart LR
A["Multiple Ultrasound<br/>Beams"] --> B["Converge at<br/>Target STN"]
B --> C["Rapid Heating<br/>55-65°C"]
C --> D["Thermal<br/>Coagulation"]
D --> E["Targeted<br/>Lesion"]
-
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
| 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 |
- Age: 40-75 years
- Diagnosis: Clinically confirmed Parkinson's disease
- Disease Stage: Hoehn & Yahr stage 1-2 (early-stage)
- Motor Symptoms: Predominant unilateral symptoms (Hoehn & Yahr ≤2 on most affected side)
- Disease Duration: 1-10 years since diagnosis
- Levodopa Response: ≥30% improvement in MDS-UPDRS Part III
- Stable Medications: No changes in PD medications for 30 days
- Ability to undergo MRI: No contraindication
- Atypical Parkinsonism: PSP, MSA, CBD
- Dementia: MMSE ≤24 or clinical diagnosis
- Psychiatric Comorbidities: Active psychosis, severe depression
- Brain Abnormalities: Prior intracranial surgery, hemorrhage, tumor
- Coagulopathy: Anticoagulation cannot be held
- Pregnancy: Female patients of childbearing potential
- Implants: Contraindicated ferromagnetic devices
| 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 |
| Measure |
Timepoint |
Description |
| Quality of Life |
3, 6, 12 months |
PDQ-39 score |
| Motor Fluctuations |
12 months |
Change in "ON"/"OFF" time |
| Levodopa Dose |
12 months |
Percentage reduction |
| Dyskinesia |
12 months |
Change in UDysRS score |
| Cognitive Function |
3, 12 months |
MoCA score |
| Mood |
3, 12 months |
BDI-II score |
- DAT-scan changes
- CSF biomarker levels
- Neural correlates of improvement
| Factor |
MRgFUS Subthalamotomy |
Deep Brain Stimulation |
| Invasiveness |
Non-invasive |
Invasive (drilling) |
| Hospital Stay |
Outpatient possible |
2-5 days |
| Recovery |
Immediate |
Weeks to months |
| Reversibility |
Permanent lesion |
Reversible |
| Infection Risk |
None |
3-5% |
| Hardware |
None |
Permanent implants |
- Preserves Surgical Options: Does not preclude future DBS
- Reduces Medication Exposure: May allow lower levodopa doses
- Prevents Complications: May reduce dyskinesia development
- Maintains Quality of Life: Earlier return to function
| Trial |
Intervention |
Stage |
Target |
| This trial (NCT06584383) |
MRgFUS STN |
Phase 2 |
Early PD |
| EARLYSTIM |
DBS STN |
Phase 3 |
Early PD |
| LEAPS-STN |
Levodopa |
Phase 3 |
De novo PD |
- NCT06584383: MR-Guided Focused Ultrasound Subthalamotomy for Early-Stage Parkinson's Disease
- Subthalamic focused ultrasound in Parkinson's disease (2024)
- Focused ultrasound subthalamotomy for Parkinson's disease: a randomised controlled trial (2024)
- Long-term outcomes of focused ultrasound thalamotomy (2024)
- A randomized trial of focused ultrasound thalamotomy for essential tremor (2023)
- InSightec Ltd. - MR-Guided Focused Ultrasound Technology