Ignite Creation Date:
2025-12-24 @ 4:54 PM
Ignite Modification Date:
2025-12-29 @ 12:26 AM
Study NCT ID:
NCT07168850
Status:
RECRUITING
Last Update Posted:
2025-09-11
First Post:
2025-08-20
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Focused Ultrasound Unilateral Pallidotomy for Medication-Refractory Limb Dystonia
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D004421', 'term': 'Dystonia'}, {'id': 'D020821', 'term': 'Dystonic Disorders'}], 'ancestors': [{'id': 'D020820', 'term': 'Dyskinesias'}, {'id': 'D009461', 'term': 'Neurologic Manifestations'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D009069', 'term': 'Movement Disorders'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'OUTCOMES_ASSESSOR'], 'maskingDescription': 'Double-blind (Participant, Care Provider, Outcomes Assessor)'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': '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.'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 34}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2025-01-27', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-09', 'completionDateStruct': {'date': '2027-02-28', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-09-04', 'studyFirstSubmitDate': '2025-08-20', 'studyFirstSubmitQcDate': '2025-09-04', 'lastUpdatePostDateStruct': {'date': '2025-09-11', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2025-09-11', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2027-02-28', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Chenge in the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS)', 'timeFrame': 'Baseline to Week 12', 'description': 'The BFMDRS has a maximum score of 120 for the movement subscale and 30 for the disability subscale. Higher scores indicating more severe dystonia.'}], 'secondaryOutcomes': [{'measure': 'Incidence of treatment-related adverse events', 'timeFrame': 'Baseline to Week 24', 'description': 'Assessment of any treatment-related adverse events throughout the whole study period'}, {'measure': 'Changes in the Quick Disabilities of Arm, Shoulder & Hand (Quick-DASH) score', 'timeFrame': 'Baseline, Week 12 and Week 24', 'description': '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.'}, {'measure': 'Changes in the Clinical Global Impression of Change (CGIC) score', 'timeFrame': 'Baseline, week 12 and week 24', 'description': "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."}, {'measure': 'Patient Global Impression of Change (PGIC)', 'timeFrame': 'Baseline, Week 12 and week 24', 'description': 'The maximum score of the PGIC is 7: the higher the score the higher the improvement reported by a patient.'}, {'measure': 'Change in the 36-Item Short Form Survey (SF-36) score', 'timeFrame': 'Baseline, week 12 and week 24', 'description': '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.'}, {'measure': 'Changes in the Short-Interval Cortical Inhibition (SICI)', 'timeFrame': 'Baseline and Week 24', 'description': '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'}, {'measure': 'Changes in intracortical facilitation (ICF)', 'timeFrame': 'Baseline and Week 24', 'description': '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'}, {'measure': 'Changes in Paired Associative Stimulation (PAS)', 'timeFrame': 'Baseline and week 24', 'description': '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'}, {'measure': 'Changes in brain activity (using functional connectivity) using resting-state functional magnetic resonance imaging (rs-fMRI)', 'timeFrame': 'Baseline and Week 24', 'description': 'The investigators will conduct a region-of-interest analysis to calculate changes of fMRI functional connectivity between baseline and post-pallidotomy.'}, {'measure': 'Changes in pallidotomy lesion morphology via contrast MRI', 'timeFrame': '24-hour after the procedure, week 12 and week 24', 'description': '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.'}, {'measure': 'Changes in the Montreal Cognitive Assessment (MoCA) score', 'timeFrame': 'Baseline, week 12 and week 24', 'description': 'This 30-point test investigates global cognitive functions. The lower the score the worse the cognitive functions.'}, {'measure': 'Change in Digit Span test score', 'timeFrame': 'Baseline, week 12 and week 24]', 'description': 'This is a cognitive test investigating memory functions. The lower the socre, the greater the impairment'}, {'measure': 'Change in the Stroop Test score', 'timeFrame': 'Baseline, week 12 and week 24', 'description': 'This is a neuropsychological test measuring frontl-lobe cognitive function. High scores or slower reaction times indicate worse executive cognitive functions'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Focused Ultrasound', 'MRgFUS', 'Pallidotomy', 'Dystonia', 'Exablate', 'Neuromodulation', 'fMRI', 'TMS'], 'conditions': ['Limb Dystonia', 'Idiopathic Dystonia', 'Medication-refractory Dystonia', 'Dystonia, Focal']}, 'referencesModule': {'references': [{'pmid': '10590980', 'type': 'BACKGROUND', 'citation': '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': '15455393', 'type': 'BACKGROUND', 'citation': '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': '3966004', 'type': 'BACKGROUND', 'citation': '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': '34050695', 'type': 'BACKGROUND', 'citation': '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': '35844284', 'type': 'BACKGROUND', 'citation': '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': '36812432', 'type': 'BACKGROUND', 'citation': "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': '36906335', 'type': 'BACKGROUND', 'citation': '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': '33720521', 'type': 'BACKGROUND', 'citation': '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': '33215750', 'type': 'BACKGROUND', 'citation': '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': '23893456', 'type': 'BACKGROUND', 'citation': 'Jankovic J. Medical treatment of dystonia. Mov Disord. 2013 Jun 15;28(7):1001-12. doi: 10.1002/mds.25552.'}, {'pmid': '19103214', 'type': 'BACKGROUND', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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.\n\nThe main questions it aims to answer are:\n\n* Does focused ultrasound reduce the severity of limb dystonia symptoms?\n* Is the procedure safe and well tolerated?\n\nResearchers 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.\n\nFocused 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.\n\nParticipants will:\n\n* Be randomly assigned to one of two groups: focused ultrasound or sham\n* Undergo a procedure using MRI and focused ultrasound to target a part of the brain called the globus pallidus\n* Be followed for 6 months after treatment to assess changes in symptoms, quality of life, and brain function\n* Participants in the sham group will be offered the real treatment after 3 months\n\nThis study may offer a new non-surgical treatment option for people with dystonia affecting the arm or leg, whose pharmacological control is unsatisfactory.', 'detailedDescription': '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.\n\nDystonia 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.\n\nRecent 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.\n\nThe 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:\n\n* an active treatment group, undergoing unilateral GPi lesioning via MRgFUS,\n* or a sham control group, receiving the same procedural setup but without therapeutic sonications.\n\nAt 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.\n\nThe 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.\n\nAdditionally, 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.\n\nThe 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '80 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Age 18-80 years\n* Able and willing to consent and attend visits\n* Idiopathic or hereditary limb dystonia (focal, segmental, or multifocal; isolated or combined)\n* Refractory to oral therapy and botulinum toxin\n* Stable medication for ≥30 days and ≥90 days since last BoNT\n* Capable of communicating during Exablate procedure\n\nExclusion Criteria:\n\n* Acquired secondary dystonia\n* Dementia or other neurodegenerative disorders\n* 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)\n* Prior deep brain stimulation or other brain surgery\n* Any contraindication to MRI\n* Skull Density Ratio (SDR) \\< 0.40\n* Significant brain lesions (eg brain tumor, significant white matter lesions or globus pallidus interna lesions on baseline MRI)\n* Pregnancy'}, 'identificationModule': {'nctId': 'NCT07168850', 'acronym': 'FUTURE', 'briefTitle': 'Focused Ultrasound Unilateral Pallidotomy for Medication-Refractory Limb Dystonia', 'organization': {'class': 'OTHER', 'fullName': 'Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta'}, 'officialTitle': 'Focused Ultrasound Pallidotomy for Medication-Refractory Limb Dystonia (FUTURE Study)', 'orgStudyIdInfo': {'id': 'PNRR-MCNT2-2023-12378417'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Active Pallidotomy (MRgFUS)', 'description': 'Patients undergo unilateral pallidotomy using Exablate system under MRI guidance.', 'interventionNames': ['Device: Exablate MR-guided Focused Ultrasound Pallidotomy']}, {'type': 'SHAM_COMPARATOR', 'label': 'Sham Procedure', 'description': 'Identical setup without thermal lesioning. Participants cross over to active Pallidotomy after 3 months.', 'interventionNames': ['Device: Exablate MR-guided Focused Ultrasound Pallidotomy', 'Device: Sham Sham Exablate MRgFUS Pallidotomy']}], 'interventions': [{'name': 'Exablate MR-guided Focused Ultrasound Pallidotomy', 'type': 'DEVICE', 'description': 'Active Pallidotomy', 'armGroupLabels': ['Active Pallidotomy (MRgFUS)', 'Sham Procedure']}, {'name': 'Sham Sham Exablate MRgFUS Pallidotomy', 'type': 'DEVICE', 'description': 'Sham procedure. Identical setup without thermal lesioning. Participants cross over to Active Pallidotomy after 3 months.', 'armGroupLabels': ['Sham Procedure']}]}, 'contactsLocationsModule': {'locations': [{'zip': '30174', 'city': 'Mestre', 'state': '(Venice)', 'status': 'RECRUITING', 'country': 'Italy', 'contacts': [{'name': 'Rocco Quatrale', 'role': 'CONTACT', 'email': 'rocco.quatrale@aulss3.veneto.it', 'phone': '+390419657387'}, {'name': 'Rocco Quatrale', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Azienda ULSS3 Serenissima', 'geoPoint': {'lat': 45.49167, 'lon': 12.24538}}, {'zip': '98124', 'city': 'Messina', 'status': 'RECRUITING', 'country': 'Italy', 'contacts': [{'name': 'Silvia Marino', 'role': 'CONTACT', 'email': 'silvia.marino@irccsme.it'}, {'name': 'Silvia Marino', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'IRCCS Centro Neurolesi "Bonino-Pulejo"', 'geoPoint': {'lat': 38.19394, 'lon': 15.55256}}, {'zip': '20133', 'city': 'Milan', 'status': 'RECRUITING', 'country': 'Italy', 'contacts': [{'name': 'Roberto Eleopra', 'role': 'CONTACT', 'email': 'roberto.eleopra@istituto-besta.it', 'phone': '+390223942552'}, {'name': 'Giovanna Zorzi', 'role': 'CONTACT', 'email': 'giovanna.zorzi@istituto-besta.it', 'phone': '+39 0223942712'}, {'name': 'Giovanna Zorzi', 'role': 'PRINCIPAL_INVESTIGATOR'}, {'name': 'Roberto Eleopra', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Vincenzo Levi', 'role': 'SUB_INVESTIGATOR'}], 'facility': 'Fondazione IRCCS Istituto Neurologico Carlo Besta', 'geoPoint': {'lat': 45.46427, 'lon': 9.18951}}, {'zip': '90146', 'city': 'Palermo', 'status': 'RECRUITING', 'country': 'Italy', 'contacts': [{'name': 'Marcello C Romano', 'role': 'CONTACT', 'email': 'mc.romano1958@gmail.com'}, {'name': 'Marcello C Romano', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Azienda Ospedaliera Ospedali Riuniti Villa Sofia', 'geoPoint': {'lat': 38.1166, 'lon': 13.3636}}], 'centralContacts': [{'name': 'Roberto Eleopra', 'role': 'CONTACT', 'email': 'roberto.eleopra@istituto-besta.it', 'phone': '+390223942552'}, {'name': 'Giovanna Zorzi', 'role': 'CONTACT', 'email': 'giovanna.zorzi@istituto-besta.it', 'phone': '+390223942712'}]}, 'ipdSharingStatementModule': {'timeFrame': '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', 'ipdSharing': 'YES', 'description': 'Data will be shared upon reasonable request with appropriate safeguards for privacy and confidentiality', 'accessCriteria': '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'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta', 'class': 'OTHER'}, 'collaborators': [{'name': 'Azienda ULSS 3 Serenissima', 'class': 'OTHER'}, {'name': 'IRCCS Centro Neurolesi Bonino Pulejo', 'class': 'OTHER'}, {'name': 'Azienda Ospedaliera Villa Sofia', 'class': 'UNKNOWN'}], 'responsibleParty': {'type': 'SPONSOR'}}}}