Predictors and Mechanisms of Tremor Relapse After MR-Guided Focused Ultrasound Thalamotomy in Parkinson's Disease
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Sustained tremor reduction at 24 months
研究概览
简要总结
This study investigates magnetic resonance-guided focused ultrasound thalamotomy (MRgFUSth) for people with Parkinson's disease (PD) and tremor not responding to conventional standard doses of dopamine replacement therapy. The aim is to identify clinical and imaging biomarkers predictive of sustained tremor control up to 24 months after MRgFUSth treatment. Participants will undergo a suprathreshold levodopa test and ¹⁸F-DOPA PET imaging to evaluate dopaminergic and serotonergic involvement in tremor. All participants will receive MRgFUSth and be followed for 24 months with standardized clinical, cognitive, and quality-of-life assessments. The study seeks to improve understanding the possible mechanisms of tremor relapse and inform patient selection for MRgFUSth in PD.
详细描述
Background
Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide, affecting approximately 2% of people over 65 years of age. The pathological hallmark of PD is the progressive degeneration of dopaminergic neurons in the substantia nigra, and the cardinal clinical features are bradykinesia, rigidity, and resting tremor.
Dopaminergic dysfunction within the striatum closely correlates with the severity of bradykinesia and rigidity. However, this relationship is less consistent for resting tremor, which likely reflects the involvement of additional neurotransmitter systems. While dopamine replacement therapy (DRT) is mostly effective for bradykinesia and rigidity, the effect on resting tremor is more variable.
Positron emission tomography (PET) findings indicate that tremor-dominant Parkinson's disease (TDPD), compared with the akinetic-rigid subtype, is characterized by relatively greater serotonergic than dopaminergic dysfunction. Previous studies have used the raphe nuclei and putamen as markers of serotonergic and dopaminergic terminal integrity, respectively. The interindividual relationship between serotonergic and dopaminergic terminal integrity can thus be expressed by the raphe/putamen specific binding ratio. Reduced integrity of the serotonergic system relative to dopaminergic integrity (low raphe/putamen ratio) has been associated with higher tremor amplitude and may partly account for the limited responsiveness of tremor to DRT compared with bradykinesia and rigidity.
Medical-refractory tremor is a clinical challenge and highlights the need for non-pharmacological treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Established diagnosis of idiopathic Parkinson's disease
- •Tremor not manageable with optimal medication
- •Clinical Indication for MRgFUSth
- •Able to understand study requirements and provide consent
- •HOEHN and YAHR <3
排除标准
- •Dementia or severe cognitive impairment
- •The presence of another significant neurological/psychiatric disorder or significant disease
- •Severe psychopathology, not medically managed
- •Poor balance and gait function based on neurological examination
- •Active drug abuse
- •History of stroke or structural lesions on MRI that could interfere with image analysis.
- •Contraindications for MRI
- •Cardiac pacemaker
- •Pregnancy or breast-feeding
- •Claustrophobia
- •Patients unable to lie on the back for 2-4 hours in the MR-scanner-setting
- •Patients who do not want information about findings of unknown disease during the trial
- •SDR (Skull density rate) lower than 0.35
研究组 & 干预措施
MR-guided focused ultrasound thalamotomy (MRgFUSth) in Parkinson's tremor
MR-guided focused ultrasound thalamotomy of the ventral intermediate nucleus of the thalamus in participants with Parkinson's and tremor. Baseline and follow-up assessments for 24 months
干预措施: MR-guided focused ultrasound thalamotomy (Procedure)
结局指标
主要结局
Sustained tremor reduction at 24 months
时间窗: From pre-intervention baseline and 24 months after intervention
Number of participants with sustained tremor reduction (defined as ≥50% improvement from pre-surgical baseline) at 24 months in each group. Tremor will be evaluated using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Part III: Motor Examination Part III total tremor subscore, items 3.15-3.18 (0-40 points, lower scores indicate better outcome) The main analysis will compare the number of patients with sustained tremor control at 24 months between the Dopamine-responsive and the Dopamine-resistant group
Mean Tremor Reduction (%)
时间窗: Pre-intervention baseline until 24-months after intervention
Mean percent change from pre-surgical baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Part III: Motor Examination Part III total tremor subscore, items 3.15-3.18 (0-40 points, lower scores indicate better outcome) at each follow-up visit (24 hours, 6, 12, 18, and 24 months) in the Dopamine-responsive and Dopamine-resistant groups.
Time to relapse of tremor
时间窗: From intervention until 24-month after intervention
Proportion of participants who have relapse of tremor at any post-operative follow-up over 24 months in the Dopamine-responsive and Dopamine-resistant groups. Main analysis will evaluate the time points of which relapse occur and differences between the groups Relapse is defined as a decline of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Part III: Motor Examination Part III total tremor subscore, items 3.15-3.18 (0-40 points) to \<50% improvement relative to the pre-surgical baseline
次要结局
- Changes in Activity of daily living(Pre-intervention baseline until 24 month after intervention)
- Troublesome Tremor Relapse (PGIC-Defined)(Pre-intervention baseline until 24 month after intervention)
- Change in quality-of-life (QoL) scores from baseline to 24 months(Baseline until 24 month post-intervention)
- Adverse effects(Baseline until 24 months post-intervention)
- Change in cognitive performance (MoCA score) from baseline to follow-up(Pre-intervention baseline until 24 month after intervention)
- Change in Levodopa Equivalent Daily Dose (LEDD) from baseline to 24 months.(Pre-intervention baseline until 24 month after intervention)
研究者
Andreas Nørgaard Glud
Associate Professor of Neurosurgery
Aarhus University Hospital