Category: Parkinson’s Disease: Clinical Trials
Objective: To describe the protocol of a multicenter, prospective, randomized controlled trial (EarlyFocus II) which evaluates the efficacy and safety of unilateral magnetic resonance-guided focused ultrasound subthalamotomy (STN-MRgFUS) in patients with early-stage Parkinson’s disease (ESPD) (i.e., <5 years from diagnosis).
Background: Unilateral STN-MRgFUS improves motor manifestations in patients with PD.1 A pilot study suggested it may also be effective in patients with ESPD.2
Method: People with PD of less than 5 years and Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) motor score £32 will be randomized 2:1 (n=36:18) to receive STN-MRgFUS or best medical treatment (BMT), respectively (Figure 1). Participating centers had extensive experience in functional neurosurgery, including STN-MRgFUS for PD. The primary efficacy endpoint is the between-group difference (STN-MRgFUS vs. BMT) in the change in the MDS-UPDRS Part III score off-medication at 12 months. Safety endpoint includes treatment-related adverse events. Secondary endpoints are changes in brain PD-related metabolic pattern (using 18F-fluorodeoxyglucose-PET), MDS-UPDRS I, II, IV, Unified Dyskinesia Rating Scale, PD-39 questionnaire and MDS-NMSS. Exploratory endpoints include striatal dopaminergic denervation (using 18F-fluorodihydroxyphenylalanine-PET) and time to PD progression milestones. The skull density ratio will serve for patient arm allocation3 adding a BMT arm to extend the long-term (36-month) follow-up pool, allowing for further comparison and disease progression assessment.
Results: Twenty-nine patients have been enrolled so far: 16 STN-MRgFUS, 8-BMT, 2 Low SDR, 2 are awaiting randomization.
Conclusion: This randomized controlled trial primary aim is to evaluate the efficacy and safety of unilateral STN-MRgFUS in patients with ESPD. Furthermore, it will assess any effect on disease progression.
Earlyfocus II trial design
References: 1. Martínez-Fernández R, Máñez-Miró JU, Rodríguez-Rojas R, et al. Randomized Trial of Focused Ultrasound Subthalamotomy for Parkinson’s Disease. N Engl J Med. 2020;383(26):2501-2513. doi:10.1056/nejmoa2016311
2. Martínez Fernández R, Natera Villalba E, Rodriguez-Rojas R, et al. Unilateral focused ultrasound subthalamotomy in early Parkinson’s disease: a pilot study. J Neurol Neurosurg Psychiatry. 2023;95(3):206-213. doi:10.1136/jnnp-2023-331211
3. Pineda‐Pardo JA, Martínez‐Fernández R, Natera‐Villalba E, et al. Skull Density Ratio as Arm‐Allocation Parameter for a Controlled Focused Ultrasound Trial in Parkinson’s Disease. Mov Disord Clin Pract. 2024;11(7):825-829. doi:10.1002/mdc3.14040
To cite this abstract in AMA style:
R. Martinez-Fernandez, MC. Rodriguez Oroz, S. Paschen, C. Juri, M. Del Alamo, E. Natera-Villalba, R. Rodriguez-Rojas, LH. Gonzalez-Quarante, M. Synowitz, J. Lorenzoni, CA. Sánchez-Catasús, S. Obika, T. Jimenez-Castellanos, P. Reiters, E. Cerutti, RA. Villino-Boquete, C. Ferrer, O. Rascol, G. Deuschl, JA. Obeso. Unilateral focused ultrasound subthalamotomy in early Parkinson’s disease: randomized-controlled trial protocol [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/unilateral-focused-ultrasound-subthalamotomy-in-early-parkinsons-disease-randomized-controlled-trial-protocol/. Accessed October 5, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/unilateral-focused-ultrasound-subthalamotomy-in-early-parkinsons-disease-randomized-controlled-trial-protocol/