Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Michael J. Fox Foundation for Parkinson's Research | OTHER |
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| [standard STN] + swallowing therapy | Active Comparator | standard stimulation on subthalamic (STN) contacts plus swallowing therapy |
|
| [STN+SNr] + swallowing therapy | Experimental | Combined stimulation of the subthalamic nucleus (STN) and the substantia nigra pars reticulata (SNr) plus swallowing therapy |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| [standard STN] | Device | standard stimulation on subthalamic (STN) contacts High frequency deep brain stimulation with variable (best individual) stimulation on subthalamic contacts |
| Measure | Description | Time Frame |
|---|---|---|
| Penetration Aspiration Scale | 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 | Outcome after eight weeks (V2) with reference to baseline (V1) |
| Measure | Description | Time Frame |
|---|---|---|
| MDS-UPDRS parts I, II, III and IV | Rating Scale for symptoms of Parkinson's Disease: I Non-motor Experiences of Daily Living; II: Motor Experiences of Daily Living; III: Motor Examination; IV: Motor Complications. | Outcome after eight weeks (V2) with reference to baseline (V1) |
| Capsit-PD |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Daniel Weiss, MD | Contact | 0049-7071-29-82340 | daniel.weiss@uni-tuebingen.de | |
| Alireza Gharabaghi, MD | Contact | 0049-7071-29-83550 | alireza.gharabaghi@uni-tuebingen.de |
| Name | Affiliation | Role |
|---|---|---|
| Daniel Weiss, MD | University Hospital Tuebingen | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Tübingen | Recruiting | Tübingen | 72076 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23757762 | Background | Weiss D, Walach M, Meisner C, Fritz M, Scholten M, Breit S, Plewnia C, Bender B, Gharabaghi A, Wachter T, Kruger R. Nigral stimulation for resistant axial motor impairment in Parkinson's disease? A randomized controlled trial. Brain. 2013 Jul;136(Pt 7):2098-108. doi: 10.1093/brain/awt122. Epub 2013 Jun 11. | |
| 27043290 | Background |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D010300 | Parkinson Disease |
| D003680 | Deglutition Disorders |
| D020734 | Parkinsonian Disorders |
| D019636 | Neurodegenerative Diseases |
| D009069 | Movement Disorders |
| D009422 | Nervous System Diseases |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| ID | Term |
|---|---|
| D000080874 | Synucleinopathies |
| D004935 | Esophageal Diseases |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| [STN+SNr] | Device | Combined stimulation of the subthalamic nucleus (STN) and the substantia nigra pars reticulata (SNr) high frequency deep brain stimulation of combined (best individual) subthalamic and nigral stimulation |
|
|
| Swallowing therapy | Behavioral | Swallowing therapy with speech therapist |
|
Walking distance of 7m. Patient has to walk that distance back and forth. The time is measured as well as the number of steps needed for each way. Also, freezing episodes are counted. |
| Outcome after eight weeks (V2) with reference to baseline (V1) |
| Freezing of Gait Assessment Course (FOG-AC) | Patients were asked to sit down on a chair, then stand up and walk to a floor mark .Within the mark they performed two 360° turns, clockwise (cw) and counter-clockwise (ccw). Then: open and walk through the door, turn outside, and come back to their chair. Four situations were rated: The start to walk, the turning (cw and ccw), and the passing through the door. 0 points: no festination and no FOG , 1 point: festination or any hastening steps. 2 points: FOG (trembling-in-place or total akinesia), which the patient could overcome himself. 3points: abortion of the task or need of interference by the examiner. Three levels of multiple tasking were applied: First passage;: no additional task ("walking"). Second passage: carrying a tray with a plastic cup full of water. Third passage: motor task and a mental task ("carrying and calculation"). (Ziegler et al. 2010) | Outcome after eight weeks (V2) with reference to baseline (V1) |
| PDQ-39 | The 39-item Parkinson's Disease Questionnaire is a widely used patient-reported clinical trial endpoint, where patients are asked about their health-related quality of life related to Parkinson's disease. | Outcome after eight weeks (V2) with reference to baseline (V1) |
| Dysphagia-related Quality of Life (SWAL-QoL) | 48-item quality-of-life outcomes tool for dysphagia researchers and clinicians | Outcome after eight weeks (V2) with reference to baseline (V1) |
| Clinical global impression self | (self-reporting, caregiver-reporting) | Outcome after eight weeks (V2) |
| Diary on swallowing an related complications | complications (cough, suffocation, bronchitis, aspiration pneumonia) | Outcome after eight weeks (V2) with reference to baseline (V1) |
| Site of Swallow reflex initiation | Two FEES outcome variables-delayed initiation of the pharyngeal reflex and postswallow pyriform sinus pooling(Scott et al 1998) | Outcome after eight weeks (V2) with reference to baseline (V1) |
| Test of Mastication and Swallowing solids (TOMASS) | The Test of Masticating and Swallowing Solids (TOMASS) was developed as a quantitative assessment of solid bolus ingestion. For each study the test required participants to ingest a commercially available cracker with instructions to 'eat this as quickly as is comfortably possible'. Further averaged measures were derived including the number of masticatory cycles and swallows per bite, and time per bite, masticatory cycle and swallow. | Outcome after eight weeks (V2) with reference to baseline (V1) |
| Pharyngeal Residue Visual Analogue Scale (VAS) | With FEES the pharyngeal residue (Sinus piriformis and vallecular) are rated on a visual analogue scale | Outcome after eight weeks (V2) with reference to baseline (V1) |
| Functional oral intake scale (FOIS) | Scale to assess oral intake (7 points indicate full oral intake without restrictions, 1 points indicates no oral intake possible, 1-3 tube dependent) (Crary et al. 2005) | Outcome after eight weeks (V2) with reference to baseline (V1) |
| Rossi MA, Li HE, Lu D, Kim IH, Bartholomew RA, Gaidis E, Barter JW, Kim N, Cai MT, Soderling SH, Yin HH. A GABAergic nigrotectal pathway for coordination of drinking behavior. Nat Neurosci. 2016 May;19(5):742-748. doi: 10.1038/nn.4285. Epub 2016 Apr 4. |
| 19001482 | Background | Chastan N, Westby GW, Yelnik J, Bardinet E, Do MC, Agid Y, Welter ML. Effects of nigral stimulation on locomotion and postural stability in patients with Parkinson's disease. Brain. 2009 Jan;132(Pt 1):172-84. doi: 10.1093/brain/awn294. Epub 2008 Nov 11. |
| 29089922 | Background | Scholten M, Klemt J, Heilbronn M, Plewnia C, Bloem BR, Bunjes F, Kruger R, Gharabaghi A, Weiss D. Effects of Subthalamic and Nigral Stimulation on Gait Kinematics in Parkinson's Disease. Front Neurol. 2017 Oct 17;8:543. doi: 10.3389/fneur.2017.00543. eCollection 2017. |
| 28246572 | Background | Hidding U, Gulberti A, Horn A, Buhmann C, Hamel W, Koeppen JA, Westphal M, Engel AK, Gerloff C, Weiss D, Moll CK, Potter-Nerger M. Impact of Combined Subthalamic Nucleus and Substantia Nigra Stimulation on Neuropsychiatric Symptoms in Parkinson's Disease Patients. Parkinsons Dis. 2017;2017:7306192. doi: 10.1155/2017/7306192. Epub 2017 Jan 26. |
| 21287187 | Background | Weiss D, Breit S, Wachter T, Plewnia C, Gharabaghi A, Kruger R. Combined stimulation of the substantia nigra pars reticulata and the subthalamic nucleus is effective in hypokinetic gait disturbance in Parkinson's disease. J Neurol. 2011 Jun;258(6):1183-5. doi: 10.1007/s00415-011-5906-3. Epub 2011 Feb 2. No abstract available. |
| D010608 | Pharyngeal Diseases |
| D010038 | Otorhinolaryngologic Diseases |