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Limb DystoniaFUTURENCT07168850

Focused Ultrasound Unilateral Pallidotomy for Medication-Refractory Limb Dystonia

A study testing Exablate MR-guided Focused Ultrasound Pallidotomy in people with Limb Dystonia and Idiopathic Dystonia, run by Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta at 4 sites in Italy.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 80 years
What is being tested?
Exablate MR-guided Focused Ultrasound Pallidotomy
Type of treatment
Medical device
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
34 participants
Where
4 sitesItaly
Study dates
27 Jan 2025to 28 Feb 2027
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

4 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Roberto Eleopra contact

+390223942552

roberto.eleopra@istituto-besta.it

Giovanna Zorzi contact

+390223942712

giovanna.zorzi@istituto-besta.it

Italy4 sites, 4 recruiting

  • IRCCS Centro Neurolesi "Bonino-Pulejo"

    Messina, 98124

    Silvia Marino, silvia.marino@irccsme.it

    Silvia Marino

    Recruiting

  • Azienda ULSS3 Serenissima

    Mestre, (Venice), 30174

    Rocco Quatrale, +390419657387, rocco.quatrale@aulss3.veneto.it

    Rocco Quatrale

    Recruiting

  • Fondazione IRCCS Istituto Neurologico Carlo Besta

    Milan, 20133

    Roberto Eleopra, +390223942552, roberto.eleopra@istituto-besta.it

    Giovanna Zorzi, +39 0223942712, giovanna.zorzi@istituto-besta.it

    Recruiting

  • Azienda Ospedaliera Ospedali Riuniti Villa Sofia

    Palermo, 90146

    Marcello C Romano, mc.romano1958@gmail.com

    Marcello C Romano

    Recruiting

Other trials in Italy

About this study

Official title: Focused Ultrasound Pallidotomy for Medication-Refractory Limb Dystonia (FUTURE Study)

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:

Read more
  • 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.

Read the detailed description

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.

Being tested
Exablate MR-guided Focused Ultrasound Pallidotomy, Sham Sham Exablate MRgFUS Pallidotomy
Keywords
Focused Ultrasound, MRgFUS, Pallidotomy, Dystonia, Exablate, Neuromodulation, fMRI, TMS
Medical subject headings
Dystonia, Dystonic Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Exablate MR-guided Focused Ultrasound PallidotomyDevice

    Active Pallidotomy

  • Sham Sham Exablate MRgFUS PallidotomyDevice

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

Study groups in NCT07168850
Study groupRoleWhat they receive
Active Pallidotomy (MRgFUS)ExperimentalPatients undergo unilateral pallidotomy using Exablate system under MRI guidance.
Receives: Device: Exablate MR-guided Focused Ultrasound Pallidotomy
Sham ProcedureSham comparatorIdentical setup without thermal lesioning. Participants cross over to active Pallidotomy after 3 months.
Receives: Device: Exablate MR-guided Focused Ultrasound Pallidotomy; Device: Sham Sham Exablate MRgFUS Pallidotomy

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline to Week 12

Secondary outcomes (13)

  1. Incidence of treatment-related adverse events

    Assessment of any treatment-related adverse events throughout the whole study period

    Measured: Baseline to Week 24

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

    The QuickDASH is a shortened, 11-item version of the DASH Outcome Measure, designed to assess physical function and symptom severity related to the arm, shoulder, and hand. Maximum score 100; the greater the score the grear the disability.

    Measured: Baseline, Week 12 and Week 24

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

    The CGIC is a 7-point scale used to assess the degree of change in a patient's condition since the start of treatment or another defined baseline. Lower scores indicates improvement and higher scores indicating worsening of the patient's condition.

    Measured: Baseline, week 12 and week 24

  4. Patient Global Impression of Change (PGIC)

    The maximum score of the PGIC is 7: the higher the score the higher the improvement reported by a patient.

    Measured: Baseline, Week 12 and week 24

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

    The SF-36 questionnaire has a maximum score of 100 for each of its eight scaled scores (physical functioning, role limitations due to physical health, bodily pain, general health, vitality, social functioning, role limitations due to emotional problems, and mental health). The higher the scores the more favorable is health state within that specific dimension.

    Measured: Baseline, week 12 and week 24

  6. Changes in the Short-Interval Cortical Inhibition (SICI)

    This is a neurophysiological measure of inhibitory processes within the motor cortex, assessed using Transcranial Magnetic Stimulation, which is measured as the relative amplitude reduction of motor evoked potentials from the test stimulus when it is preceded by the conditioning stimulus. The greater the change in SICI, the greater the pallidotomy-induced changes in motor cortex intracortical inhibitory circuits

    Measured: Baseline and Week 24

  7. Changes in intracortical facilitation (ICF)

    This is a neurophysiological measures of cortical excitability, assessed using paired-pulse Transcranial Magnetic Stimulation, which describes an increase in the magnitude of a motor evoked potential in a target muscle when a suprathreshold test pulse is preceded by a subthreshold conditioning pulse at specific interstimulus intervals. The greater the change in ICF, the greater the pallidotomy-induced changes in intracortical excitatory circuits

    Measured: Baseline and Week 24

  8. Changes in Paired Associative Stimulation (PAS)

    This is a neurophysiological measure of cortical plasticity assessed using transcranial magnetic stimulation. The greater the change in PAS, the greater the pallidotomy-induced changes in motor cortex synaptic plasticity

    Measured: Baseline and week 24

  9. Changes in brain activity (using functional connectivity) using resting-state functional magnetic resonance imaging (rs-fMRI)

    The investigators will conduct a region-of-interest analysis to calculate changes of fMRI functional connectivity between baseline and post-pallidotomy.

    Measured: Baseline and Week 24

  10. Changes in pallidotomy lesion morphology via contrast MRI

    To evaluate the morphological changes of the lesion after 24 hours, 3 months and 6 months from pallidotomy using contrast-enhanced brain MRI and their relationship with clinical changes including adverse events.

    Measured: 24-hour after the procedure, week 12 and week 24

  11. Changes in the Montreal Cognitive Assessment (MoCA) score

    Changes in the Montreal Cognitive Assessment (MoCA) score, a 30-point test of global cognitive functions. Score range: 0-30, with lower scores indicating worse cognitive function and higher scores indicating better cognitive function.

    Measured: Baseline, week 12 and week 24

  12. Change in Digit Span test score

    Change in Digit Span test score, a cognitive test assessing memory functions. Score range: 0-[insert maximum score for the test], with lower scores indicating greater memory impairment and higher scores indicating better memory function.

    Measured: Baseline, week 12 and week 24]

  13. Change in the Stroop Test score

    Change in Stroop Test scores, a neuropsychological test assessing frontal-lobe executive cognitive function. Score range: [insert minimum]-[insert maximum], with higher scores or slower reaction times indicating worse executive cognitive function.

    Measured: Baseline, week 12 and week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Sep 2025
  2. Study start27 Jan 2025
  3. Primary completion28 Feb 2027 (estimated)
  4. Study completion28 Feb 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
Triple blind
Who is masked
Participant, Care provider, Outcomes assessor
Enrolment
34 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07168850
Sponsor's protocol ID
PNRR-MCNT2-2023-12378417
Acronym
FUTURE
Status last verified
Nov 2026
First submitted
20 Aug 2025
Last updated
5 Nov 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Data will be shared upon reasonable request with appropriate safeguards for privacy and confidentiality

Publications

  • 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.

    PubMed 10590980

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

    PubMed 15455393

  • 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.

    PubMed 3966004

  • 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.

    PubMed 34050695

  • 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.

    PubMed 35844284

  • 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.

    PubMed 36812432

  • 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.

    PubMed 36906335

  • 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.

    PubMed 33720521

  • 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.

    PubMed 33215750

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

    PubMed 23893456

  • 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.

    PubMed 19103214

Questions about this trial

What is this clinical trial studying?

A study testing Exablate MR-guided Focused Ultrasound Pallidotomy in people with Limb Dystonia and Idiopathic Dystonia, run by Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta at 4 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Roberto Eleopra (+390223942552, roberto.eleopra@istituto-besta.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Chenge in the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) (time frame: Baseline to Week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07168850, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.

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