Focused Ultrasound Pallidotomy for Medication-Refractory Limb Dystonia (FUTURE Study)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 34
- 试验地点
- 4
- 主要终点
- Chenge in the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
盲法说明
Double-blind (Participant, Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Active Pallidotomy (MRgFUS)
Patients undergo unilateral pallidotomy using Exablate system under MRI guidance.
干预措施: Exablate MR-guided Focused Ultrasound Pallidotomy (Device)
Sham Procedure
Identical setup without thermal lesioning. Participants cross over to active Pallidotomy after 3 months.
干预措施: Exablate MR-guided Focused Ultrasound Pallidotomy (Device)
Sham Procedure
Identical setup without thermal lesioning. Participants cross over to active Pallidotomy after 3 months.
干预措施: Sham Sham Exablate MRgFUS Pallidotomy (Device)
结局指标
主要结局
Chenge in the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS)
时间窗: Baseline to Week 12
The BFMDRS has a maximum score of 120 for the movement subscale and 30 for the disability subscale. Higher scores indicating more severe dystonia.
次要结局
- 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)
- Changes in the Short-Interval Cortical Inhibition (SICI)(Baseline and Week 24)
- Changes in intracortical facilitation (ICF)(Baseline and Week 24)
- Changes in Paired Associative Stimulation (PAS)(Baseline and week 24)
- Changes in brain activity (using functional connectivity) using resting-state functional magnetic resonance imaging (rs-fMRI)(Baseline and Week 24)
- Changes in pallidotomy lesion morphology via contrast MRI(24-hour after the procedure, week 12 and week 24)
- Changes in the Montreal Cognitive Assessment (MoCA) score(Baseline, week 12 and week 24)
- Change in Digit Span test score(Baseline, week 12 and week 24])
- Change in the Stroop Test score(Baseline, week 12 and week 24)