Focused Ultrasound Unilateral Pallidotomy for Medication-Refractory Limb Dystonia

NCT07168850 | Recruiting DMC

• 1 other identifier: PNRR-MCNT2-2023-12378417
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 4

Brief Summary

The goal of this clinical trial is to find out if a non-invasive procedure called focused ultrasound can safely and effectively treat limb dystonia in adults who have not improved with medications or botulinum toxin injections. The main questions it aims to answer are:

• Does focused ultrasound reduce the severity of limb dystonia symptoms?
• Is the procedure safe and well tolerated? Researchers will compare people who receive focused ultrasound treatment to those who receive a sham procedure (a look-alike procedure without active treatment) to see if the treatment works. Focused ultrasound works by producing a very small (millimeter-size) lesion in a deep brain region. In this study, the lesion is located in a region called globus pallidus, which helps control movement. Participants will:
• Be randomly assigned to one of two groups: focused ultrasound or sham
• Undergo a procedure using MRI and focused ultrasound to target a part of the brain called the globus pallidus
• Be followed for 6 months after treatment to assess changes in symptoms, quality of life, and brain function
• Participants in the sham group will be offered the real treatment after 3 months This study may offer a new non-surgical treatment option for people with dystonia affecting the arm or leg, whose pharmacological control is unsatisfactory.

Conditions

Idiopathic Dystonia; Dystonia, Focal; Limb Dystonia; Medication-refractory Dystonia

Keywords

Focused Ultrasound; MRgFUS; Pallidotomy; Dystonia; Exablate; Neuromodulation; fMRI; TMS

Outcome Measures

Primary Outcomes (1)

• Chenge in the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS)

  The BFMDRS has a maximum score of 120 for the movement subscale and 30 for the disability subscale. Higher scores indicating more severe dystonia.

  Baseline to Week 12

Secondary Outcomes (13)

• Incidence of treatment-related adverse events

  Baseline to Week 24

• Changes in the Quick Disabilities of Arm, Shoulder & Hand (Quick-DASH) score

  Baseline, Week 12 and Week 24

• Changes in the Clinical Global Impression of Change (CGIC) score

  Baseline, week 12 and week 24

• Patient Global Impression of Change (PGIC)

  Baseline, Week 12 and week 24

• Change in the 36-Item Short Form Survey (SF-36) score

  Baseline, week 12 and week 24

Study Arms (2)

Active Pallidotomy (MRgFUS)

EXPERIMENTAL

Patients undergo unilateral pallidotomy using Exablate system under MRI guidance.

Device: Exablate MR-guided Focused Ultrasound Pallidotomy

Sham Procedure

SHAM COMPARATOR

Identical setup without thermal lesioning. Participants cross over to active Pallidotomy after 3 months.

Device: Exablate MR-guided Focused Ultrasound Pallidotomy; Device: Sham Sham Exablate MRgFUS Pallidotomy

Interventions

Sham Sham Exablate MRgFUS Pallidotomy DEVICE

Sham procedure. Identical setup without thermal lesioning. Participants cross over to Active Pallidotomy after 3 months.

Sham Procedure

Exablate MR-guided Focused Ultrasound Pallidotomy DEVICE

Active Pallidotomy

Active Pallidotomy (MRgFUS); Sham Procedure

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-80 years
• Able and willing to consent and attend visits
• Idiopathic or hereditary limb dystonia (focal, segmental, or multifocal; isolated or combined)
• Refractory to oral therapy and botulinum toxin
• Stable medication for ≥30 days and ≥90 days since last BoNT
• Capable of communicating during Exablate procedure

You may not qualify if:

• Acquired secondary dystonia
• Dementia or other neurodegenerative disorders
• Any clinically significant or unstable medical condition, which, in the opinion of the principal investigator or the clinician delegated by the principal investigator, may put the participant at risk when participating in the study (e.g., unstable heart disease or coagulopathy; uncontrolled psychiatric comorbidity)
• Prior deep brain stimulation or other brain surgery
• Any contraindication to MRI
• Skull Density Ratio (SDR) \< 0.40
• Significant brain lesions (eg brain tumor, significant white matter lesions or globus pallidus interna lesions on baseline MRI)
• Pregnancy

Sponsors & Collaborators

• Azienda ULSS 3 Serenissima: collaborator
• IRCCS Centro Neurolesi Bonino Pulejo: collaborator
• Azienda Ospedaliera Villa Sofia: collaborator
• Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta: lead

Study Sites (4)

Azienda ULSS3 Serenissima

Mestre, (Venice), 30174, Italy

RECRUITING

IRCCS Centro Neurolesi "Bonino-Pulejo"

Messina, 98124, Italy

RECRUITING

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, 20133, Italy

RECRUITING

Azienda Ospedaliera Ospedali Riuniti Villa Sofia

Palermo, 90146, Italy

RECRUITING

Related Publications (11)

• Rothwell JC, Hallett M, Berardelli A, Eisen A, Rossini P, Paulus W. Magnetic stimulation: motor evoked potentials. The International Federation of Clinical Neurophysiology. Electroencephalogr Clin Neurophysiol Suppl. 1999;52:97-103. No abstract available.

  PMID: 10590980 BACKGROUND

• Sohn YH, Hallett M. Disturbed surround inhibition in focal hand dystonia. Ann Neurol. 2004 Oct;56(4):595-9. doi: 10.1002/ana.20270.

  PMID: 15455393 BACKGROUND

• Burke RE, Fahn S, Marsden CD, Bressman SB, Moskowitz C, Friedman J. Validity and reliability of a rating scale for the primary torsion dystonias. Neurology. 1985 Jan;35(1):73-7. doi: 10.1212/wnl.35.1.73.

  PMID: 3966004 BACKGROUND

• Horisawa S, Yamaguchi T, Abe K, Hori H, Fukui A, Iijima M, Sumi M, Hodotsuka K, Konishi Y, Kawamata T, Taira T. Magnetic Resonance-Guided Focused Ultrasound Thalamotomy for Focal Hand Dystonia: A Pilot Study. Mov Disord. 2021 Aug;36(8):1955-1959. doi: 10.1002/mds.28613. Epub 2021 May 29.

  PMID: 34050695 BACKGROUND

• Stieglitz LH, Mahendran S, Oertel MF, Baumann CR. Bilateral Focused Ultrasound Pallidotomy for Parkinson-Related Facial Dyskinesia-A Case Report. Mov Disord Clin Pract. 2022 May 9;9(5):647-651. doi: 10.1002/mdc3.13462. eCollection 2022 Jul.

  PMID: 35844284 BACKGROUND

• Krishna V, Fishman PS, Eisenberg HM, Kaplitt M, Baltuch G, Chang JW, Chang WC, Martinez Fernandez R, Del Alamo M, Halpern CH, Ghanouni P, Eleopra R, Cosgrove R, Guridi J, Gwinn R, Khemani P, Lozano AM, McDannold N, Fasano A, Constantinescu M, Schlesinger I, Dalvi A, Elias WJ. Trial of Globus Pallidus Focused Ultrasound Ablation in Parkinson's Disease. N Engl J Med. 2023 Feb 23;388(8):683-693. doi: 10.1056/NEJMoa2202721.

  PMID: 36812432 BACKGROUND

• Hariz M. Pros and Cons of Ablation for Functional Neurosurgery in the Neurostimulation Age. Neurosurg Clin N Am. 2023 Apr;34(2):291-299. doi: 10.1016/j.nec.2022.11.006. Epub 2023 Jan 30.

  PMID: 36906335 BACKGROUND

• Horisawa S, Fukui A, Takeda N, Kawamata T, Taira T. Safety and efficacy of unilateral and bilateral pallidotomy for primary dystonia. Ann Clin Transl Neurol. 2021 Apr;8(4):857-865. doi: 10.1002/acn3.51333. Epub 2021 Mar 15.

  PMID: 33720521 BACKGROUND

• Centen LM, Oterdoom DLM, Tijssen MAJ, Lesman-Leegte I, van Egmond ME, van Dijk JMC. Bilateral Pallidotomy for Dystonia: A Systematic Review. Mov Disord. 2021 Mar;36(3):547-557. doi: 10.1002/mds.28384. Epub 2020 Nov 20.

  PMID: 33215750 BACKGROUND

• Jankovic J. Medical treatment of dystonia. Mov Disord. 2013 Jun 15;28(7):1001-12. doi: 10.1002/mds.25552.

  PMID: 23893456 BACKGROUND

• Hallett M, Benecke R, Blitzer A, Comella CL. Treatment of focal dystonias with botulinum neurotoxin. Toxicon. 2009 Oct;54(5):628-33. doi: 10.1016/j.toxicon.2008.12.008. Epub 2008 Dec 13.

  PMID: 19103214 BACKGROUND

MeSH Terms

Conditions

Dystonia; Dystonic Disorders

Condition Hierarchy (Ancestors)

Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Movement Disorders; Central Nervous System Diseases

Central Study Contacts

Roberto Eleopra

CONTACT

+390223942552; roberto.eleopra@istituto-besta.it

Giovanna Zorzi

CONTACT

+390223942712; giovanna.zorzi@istituto-besta.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Double-blind (Participant, Care Provider, Outcomes Assessor)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 34 adult patients (17 per arm) will be randomized to receive either active MRgFUS pallidotomy or a sham procedure. Patients in the sham group will cross over to active treatment at 3 months. The follow-up period for all patients will be 6 months post-treatment.

Study Record Dates

• First Submitted: August 20, 2025
• First Posted: September 11, 2025
• Study Start: January 27, 2025
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): February 28, 2027
• Last Updated: February 11, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis
• Access Criteria: Access to trial individual participant data can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan and execution of a Data Sharing Agreement. For more information or to submit a request, please contact the P.I. of the study

Locations

IT (4)