Combined Stimulation of Subthalamic Nucleus and Substantia Nigra Pars Reticulata for Resistant Freezing of Gait in Parkinson's Disease: A Randomized Controlled Multicenter Trial
试验速览
- 阶段
- 不适用
- 入组人数
- 54
- 试验地点
- 20
- 主要终点
- Freezing of Gait Assessment Course (FOG-AC)
研究概览
简要总结
54 patients with idiopathic Parkinson's disease and freezing of gait resistant to subthalamic nucleus stimulation and dopaminergic medication will be included into this multicentre randomised controlled double-blinded parallel group clinical trial. The treatment consists of two different stimulation settings using (i) conventional stimulation of the subthalamic nucleus [standard STN] as active comparator and (ii) combined stimulation of active electrode contacts located in both the subthalamic nucleus and substantia nigra pars reticulata [STN+SNr].
详细描述
The primary endpoint of this study is to investigate the efficacy and safety of combined [STN+SNr] stimulation by "interleaving stimulation" as compared to [standardSTN] after 3 months on refractory freezing of gait (FOG). The Trial is designed as superiority study with an 80% power to detect a mean improvement of 4.7 points on the Freezing of Gait Assessment Course (Ziegler et al., 2010) with one-tailed P < 0.2. To this end 54 patients will be studied. After a common baseline assessment in [standardSTN], patients will be randomized to either [standardSTN] or [STN+SNr] in 1:1 ratio (27 per arm). The primary endpoint assessment is scheduled 90 days from baseline assessment (V6). Additional interim visits are scheduled for secondary purpose from baseline at day 2 (V2), day 8 (V3), day 21 (V4), day 42 (V5).
The rationale for this study comes from our previous phase II trial (Weiss et al., 2013) in which we have observed an improvement of freezing of gait from combined STN+SNr stimulation as secondary endpoint compared with standard STN stimulation at three-week follow-up.
Secondary outcome measures include anamnestic assessments on freezing of gait and falls, balance, quality of life, neuropsychiatric symptoms and suicidality.
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)
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
- •Idiopathic Parkinson's disease (according to the "British Brain Bank criteria" (Hughes, 1992) including genetic forms
- •Therapy with STN-DBS (deep brain stimulation) (ACTIVA pulse generators) at least six months from surgery
- •Activa PC (Primary Cell) or Activa RC (Rechargeable Cell) as implanted pulse generator with "Interleaving" programming option
- •Localization of an active electrode contact in the subthalamic nucleus
- •Localization of the caudal electrode contacts in the substantia nigra pars reticulata area (coordinates relative to midcommisural Point (MCP):
- •left: -7mm ≤ x ≤ -12mm; -2mm ≤ y ≤ -6mm; -6mm ≤ z ≤ -10mm right: 7mm ≤ x ≤ 12mm; -2mm ≤ y ≤ -6mm; -6mm ≤ z ≤ -10mm (x = medio-lateral, y = anterio-posterior, z = rostro-caudal)
- •≥ 30% improvement in UPDRS III with 'standard STN' compared to 'stimulation off' in dopaminergic off
- •Freezing of Gait Assessment Course ≥10 and ≤33
- •Patient not wheelchair-bound and possible to move self-dependently outside a freezing episode.
- •Disease duration ≥ 5 years
- •Age: between 18 and 80 years
- •Dopaminergic medication constant for at least four weeks prior to study enrolment
- •Written informed consent
排除标准
- •Participation in other clinical trials within the past three months and during enrolment in our study
- •Cognitive impairment (Mini Mental State Exam < 20)
- •Suicidality, Psychosis
- •Other severe pathological chronic condition that might confound treatment effects or interpretation of the data
- •Pregnancy
- •Paradoxical levodopa-induced "on" state freezing (Espay et al., 2012)
结局指标
主要结局
Freezing of Gait Assessment Course (FOG-AC)
时间窗: Outcome at day 90 (V6) with reference to baseline (V1)
次要结局
- Berg Balance Scale(At baseline, day 42 and 90, respectively)
- Parkinson's disease questionnaire (PDQ-39)(At baseline, day 42 and 90, respectively)
- Freezing of gait questionnaire(At baseline, day 42 and 90, respectively)
- Beck's depression Inventory(At baseline, day 42 and 90, respectively)
- Columbia-Suicide Severity Rating Scale(At baseline, day 42 and 90, respectively)
- Clinical global impression scale(At day 42 and 90, respectively)
- Timed Walking test from Core Assessment Program for Surgical Interventions in Parkinson's disease (CAPSIT-PD)(At baseline, day 2, 8, 21, 42 and 90, respectively)
- Falls diary(At baseline, day 2, 8, 21, 42 and 90, respectively)
- Movement Disorders Society Unified Parkinson's disease Rating Scale (MDS-UPDRS III)(At baseline, day 2, 8, 21, 42 and 90, respectively)
- Movement Disorders Society Unified Parkinson's disease Rating Scale (MDS-UPDRS II)(At baseline, day 42 and 90, respectively)
- Movement Disorders Society Unified Parkinson's disease Rating Scale (MDS-UPDRS IV)(At baseline, day 42 and 90, respectively)
- Freezing of Gait Assessment Course (FOG-AC)(At baseline, day 2, 8, 21, 42 after active treatment (STN vs. STN+SNr), respectively)
研究者
Daniel Weiss
MD
University Hospital Tuebingen