Combined Stimulation of Subthalamic Nucleus and Substantia Nigra Pars Reticulata for Dysphagia: A Randomized Controlled Multicenter Trial
试验速览
- 阶段
- 不适用
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Penetration Aspiration Scale
研究概览
简要总结
20 patients with idiopathic Parkinson's disease and dysphagia will be included into this 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]. Both groups receive additional swallowing therapy as standard of care.
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 8 weeks on dysphagia. The Trial is designed as superiority study with an 81% power to detect a clinically relevant mean improvement of 2 points on the Penetration Aspiration Scale for fluids (two-tailed p < 0.05). To this end 20 patients will be randomized. After a common baseline assessment in [standardSTN], patients will be randomized to either [standardSTN] or [STN+SNr] in 1:1 ratio (10 per arm). The primary endpoint assessment is scheduled 8 weeks from baseline assessment (V2). Both treatment arms will receive swallowing therapy as standard of care.
The rationale for this study comes from the association of swallowing and oral transport to neuronal integration upon the substantial nigra pars reticulate (SNr)-superior colliculus (SC) pathway (Rossi et al., 2016). Deep brain stimulation of the SNr has been put forward to modulate brainstem circuitry through its monosynaptic brainstem projections to the SC and to the pedunculopontine nucleus (PPN) (Chastan et al., 2009, Weiss et al., 2013, Rossi et al., 2016).
Secondary outcome measures include anamnestic assessments on dysphagia, clinical global impression, freezing of gait and falls, balance, quality of life, neuropsychiatric symptoms and suicidality. Secondary outcome measures also include clinical assessment of dysphagia (Site of Swallow Reflex Initiation, Test of Mastication and Swallowing solids, pharyngeal residue) as well as motor symptoms with MDS-UPDRS III, Capsit-PD and Freezing of Gait Assessment Course.
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
- •cognitive competence to consent
- •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 sub thalamic 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
- •Penetration-Aspiration-Scale ≥ 3 or more than 20% utilization of vallecular space and/or pyriform sinuses post swallowing
- •Disease duration ≥ 5 years
- •Age: between 18 and 80 years
- •Dopaminergic medication constant for at least two weeks prior to study enrollment
- •Written informed consent
排除标准
- •Participation in other clinical trials within the past three months and during study enrolment
- •Cognitive impairment (Mini Mental State Exam < 20)
- •Severe depressive episode with or without psychotic symptoms and suicidality (ICD-10: F32.2, F32.3), psychosis (ICD-10: F23.-)
- •Other severe pathological chronic condition that might confound treatment effects or interpretation of the data
- •Pregnancy
- •Infection and pneumonia at the time of study enrollment
- •Other competing cause for dysphagia (e.g. stroke, operation, radiotherapy)
结局指标
主要结局
Penetration Aspiration Scale
时间窗: Outcome after eight weeks (V2) with reference to baseline (V1)
8-point interval scale (range 1 - 8) to describe penetration and aspiration events . Scores are determined primarily by the depth to which material passes in the airway and by whether or not material entering the airway is expelled. (Rosenbek et al, 1996). The score is obtained in swallowing of fluids
次要结局
- Diary on swallowing an related complications(Outcome after eight weeks (V2) with reference to baseline (V1))
- PDQ-39(Outcome after eight weeks (V2) with reference to baseline (V1))
- Dysphagia-related Quality of Life (SWAL-QoL)(Outcome after eight weeks (V2) with reference to baseline (V1))
- Clinical global impression self(Outcome after eight weeks (V2))
- MDS-UPDRS parts I, II, III and IV(Outcome after eight weeks (V2) with reference to baseline (V1))
- Capsit-PD(Outcome after eight weeks (V2) with reference to baseline (V1))
- Site of Swallow reflex initiation(Outcome after eight weeks (V2) with reference to baseline (V1))
- Test of Mastication and Swallowing solids (TOMASS)(Outcome after eight weeks (V2) with reference to baseline (V1))
- Freezing of Gait Assessment Course (FOG-AC)(Outcome after eight weeks (V2) with reference to baseline (V1))
- Pharyngeal Residue Visual Analogue Scale (VAS)(Outcome after eight weeks (V2) with reference to baseline (V1))
- Functional oral intake scale (FOIS)(Outcome after eight weeks (V2) with reference to baseline (V1))
研究者
Daniel Weiss
Clinical Professor
University Hospital Tuebingen