Focused Ultrasound Unilateral Pallidotomy for Medication-Refractory Limb Dystonia

NCT ID: NCT07168850

Last Updated: 2025-09-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

34 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-01-27

Study Completion Date

2027-02-28

Brief Summary

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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.

Detailed Description

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The FUTURE study is a prospective, randomized, double-blind, sham-controlled, multicenter national clinical trial aimed at assessing the efficacy and safety of unilateral MR-guided focused ultrasound (MRgFUS) pallidotomy in patients with limb dystonia that is refractory to standard pharmacological treatments.

Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions, causing abnormal movements or postures. In many cases, focal or segmental dystonias affecting the limbs can be managed with oral medications and botulinum toxin (BoNT) injections. However, a subset of patients does not respond adequately to these treatments. For such individuals, surgical intervention may offer relief, yet it remains underutilized due to concerns about invasiveness and complications.

Recent advancements in non-invasive neurosurgical techniques have introduced MRgFUS pallidotomy, a procedure that uses focused ultrasound beams under real-time MRI guidance to precisely ablate small brain targets-in this case, the globus pallidus internus (GPi). The FUTURE study specifically explores this technique as a less invasive alternative to deep brain stimulation, especially for patients with focal or segmental limb dystonia who are ineligible or reluctant to undergo conventional surgery.

The trial will enroll 34 adult patients with idiopathic or genetic limb dystonia that has proven resistant to pharmacologic and BoNT treatment. These patients will be randomly assigned in a 1:1 ratio to either:

* an active treatment group, undergoing unilateral GPi lesioning via MRgFUS,
* or a sham control group, receiving the same procedural setup but without therapeutic sonications.

At three months post-randomization, all patients in the sham group will cross over to receive the active MRgFUS treatment, allowing within-subject comparisons while ensuring ethical access to the therapeutic intervention. The follow-up period for each patient will last six months after active treatment, totaling a maximum of nine months of participation.

The primary endpoint is the change in motor severity as measured by the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) at three months post-treatment. Secondary endpoints include adverse event frequency, patient and clinician global impressions of change, disability assessments (e.g., QuickDASH), quality of life (SF-36), and neurocognitive testing.

Additionally, the study will incorporate neurophysiological (TMS) and neuroimaging (resting-state fMRI) techniques to investigate treatment-induced changes in cortical excitability, plasticity, and functional connectivity, providing insight into the neural mechanisms underlying clinical improvement.

The FUTURE study is coordinated by the Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy with participation from other three major Italian neurological institutes. It represents a pioneering effort to evaluate focused ultrasound as a non-invasive therapeutic option for patients with disabling and treatment-resistant forms of limb dystonia.

Conditions

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Limb Dystonia Idiopathic Dystonia Medication-refractory Dystonia Dystonia, Focal

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors
Double-blind (Participant, Care Provider, Outcomes Assessor)

Study Groups

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Active Pallidotomy (MRgFUS)

Patients undergo unilateral pallidotomy using Exablate system under MRI guidance.

Group Type EXPERIMENTAL

Exablate MR-guided Focused Ultrasound Pallidotomy

Intervention Type DEVICE

Active Pallidotomy

Sham Procedure

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

Group Type SHAM_COMPARATOR

Exablate MR-guided Focused Ultrasound Pallidotomy

Intervention Type DEVICE

Active Pallidotomy

Sham Sham Exablate MRgFUS Pallidotomy

Intervention Type DEVICE

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

Interventions

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Exablate MR-guided Focused Ultrasound Pallidotomy

Active Pallidotomy

Intervention Type DEVICE

Sham Sham Exablate MRgFUS Pallidotomy

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

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Azienda ULSS 3 Serenissima

OTHER

Sponsor Role collaborator

IRCCS Centro Neurolesi Bonino Pulejo

OTHER

Sponsor Role collaborator

Azienda Ospedaliera Villa Sofia

UNKNOWN

Sponsor Role collaborator

Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Azienda ULSS3 Serenissima

Mestre, (Venice), Italy

Site Status RECRUITING

IRCCS Centro Neurolesi "Bonino-Pulejo"

Messina, , Italy

Site Status RECRUITING

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, , Italy

Site Status RECRUITING

Azienda Ospedaliera Ospedali Riuniti Villa Sofia

Palermo, , Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Roberto Eleopra

Role: CONTACT

+390223942552

Giovanna Zorzi

Role: CONTACT

+390223942712

Facility Contacts

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Rocco Quatrale

Role: primary

+390419657387

Silvia Marino

Role: primary

Roberto Eleopra

Role: primary

+390223942552

Giovanna Zorzi

Role: backup

+39 0223942712

Marcello C Romano

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 10590980 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 15455393 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 3966004 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34050695 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 35844284 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 36812432 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 36906335 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33720521 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33215750 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 23893456 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19103214 (View on PubMed)

Other Identifiers

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PNRR-MCNT2-2023-12378417

Identifier Type: -

Identifier Source: org_study_id

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