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Combined Stimulation of STN and SNr for Dysphagia in Parkinson's Disease

Primary Purpose

Parkinson's Disease, Dysphagia

Status
Unknown status
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
[standard STN]
[STN+SNr]
Swallowing therapy
Sponsored by
University Hospital Tuebingen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Parkinson's Disease focused on measuring Parkinson's disease, Dysphagia, Parkinsonian Disorders, Neurodegenerative Diseases, Movement Disorders, Nervous System Diseases, Basal Ganglia Diseases, Brain Diseases, Central Nervous System Diseases, Deep brain stimulation, substantia nigra pars reticulata, subthalamic nucleus

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)

Sites / Locations

  • University of TübingenRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

[standard STN] + swallowing therapy

[STN+SNr] + swallowing therapy

Arm Description

standard stimulation on subthalamic (STN) contacts plus swallowing therapy

Combined stimulation of the subthalamic nucleus (STN) and the substantia nigra pars reticulata (SNr) plus swallowing therapy

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.
Capsit-PD
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.
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)
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.
Dysphagia-related Quality of Life (SWAL-QoL)
48-item quality-of-life outcomes tool for dysphagia researchers and clinicians
Clinical global impression self
(self-reporting, caregiver-reporting)
Diary on swallowing an related complications
complications (cough, suffocation, bronchitis, aspiration pneumonia)
Site of Swallow reflex initiation
Two FEES outcome variables-delayed initiation of the pharyngeal reflex and postswallow pyriform sinus pooling(Scott et al 1998)
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.
Pharyngeal Residue Visual Analogue Scale (VAS)
With FEES the pharyngeal residue (Sinus piriformis and vallecular) are rated on a visual analogue scale
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)

Full Information

First Posted
December 30, 2017
Last Updated
May 29, 2018
Sponsor
University Hospital Tuebingen
Collaborators
Michael J. Fox Foundation for Parkinson's Research
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1. Study Identification

Unique Protocol Identification Number
NCT03470324
Brief Title
Combined Stimulation of STN and SNr for Dysphagia in Parkinson's Disease
Official Title
Combined Stimulation of Subthalamic Nucleus and Substantia Nigra Pars Reticulata for Dysphagia: A Randomized Controlled Multicenter Trial
Study Type
Interventional

2. Study Status

Record Verification Date
May 2018
Overall Recruitment Status
Unknown status
Study Start Date
April 27, 2018 (Actual)
Primary Completion Date
May 1, 2020 (Anticipated)
Study Completion Date
July 1, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital Tuebingen
Collaborators
Michael J. Fox Foundation for Parkinson's Research

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson's Disease, Dysphagia
Keywords
Parkinson's disease, Dysphagia, Parkinsonian Disorders, Neurodegenerative Diseases, Movement Disorders, Nervous System Diseases, Basal Ganglia Diseases, Brain Diseases, Central Nervous System Diseases, Deep brain stimulation, substantia nigra pars reticulata, subthalamic nucleus

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
[standard STN] + swallowing therapy
Arm Type
Active Comparator
Arm Description
standard stimulation on subthalamic (STN) contacts plus swallowing therapy
Arm Title
[STN+SNr] + swallowing therapy
Arm Type
Experimental
Arm Description
Combined stimulation of the subthalamic nucleus (STN) and the substantia nigra pars reticulata (SNr) plus swallowing therapy
Intervention Type
Device
Intervention Name(s)
[standard STN]
Other Intervention Name(s)
subthalamic deep brain stimulation
Intervention Description
standard stimulation on subthalamic (STN) contacts High frequency deep brain stimulation with variable (best individual) stimulation on subthalamic contacts
Intervention Type
Device
Intervention Name(s)
[STN+SNr]
Other Intervention Name(s)
combined subthalamic and nigral stimulation
Intervention Description
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
Intervention Type
Behavioral
Intervention Name(s)
Swallowing therapy
Intervention Description
Swallowing therapy with speech therapist
Primary Outcome Measure Information:
Title
Penetration Aspiration Scale
Description
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
Time Frame
Outcome after eight weeks (V2) with reference to baseline (V1)
Secondary Outcome Measure Information:
Title
MDS-UPDRS parts I, II, III and IV
Description
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.
Time Frame
Outcome after eight weeks (V2) with reference to baseline (V1)
Title
Capsit-PD
Description
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.
Time Frame
Outcome after eight weeks (V2) with reference to baseline (V1)
Title
Freezing of Gait Assessment Course (FOG-AC)
Description
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)
Time Frame
Outcome after eight weeks (V2) with reference to baseline (V1)
Title
PDQ-39
Description
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.
Time Frame
Outcome after eight weeks (V2) with reference to baseline (V1)
Title
Dysphagia-related Quality of Life (SWAL-QoL)
Description
48-item quality-of-life outcomes tool for dysphagia researchers and clinicians
Time Frame
Outcome after eight weeks (V2) with reference to baseline (V1)
Title
Clinical global impression self
Description
(self-reporting, caregiver-reporting)
Time Frame
Outcome after eight weeks (V2)
Title
Diary on swallowing an related complications
Description
complications (cough, suffocation, bronchitis, aspiration pneumonia)
Time Frame
Outcome after eight weeks (V2) with reference to baseline (V1)
Title
Site of Swallow reflex initiation
Description
Two FEES outcome variables-delayed initiation of the pharyngeal reflex and postswallow pyriform sinus pooling(Scott et al 1998)
Time Frame
Outcome after eight weeks (V2) with reference to baseline (V1)
Title
Test of Mastication and Swallowing solids (TOMASS)
Description
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.
Time Frame
Outcome after eight weeks (V2) with reference to baseline (V1)
Title
Pharyngeal Residue Visual Analogue Scale (VAS)
Description
With FEES the pharyngeal residue (Sinus piriformis and vallecular) are rated on a visual analogue scale
Time Frame
Outcome after eight weeks (V2) with reference to baseline (V1)
Title
Functional oral intake scale (FOIS)
Description
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)
Time Frame
Outcome after eight weeks (V2) with reference to baseline (V1)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Daniel Weiss, MD
Phone
0049-7071-29-82340
Email
daniel.weiss@uni-tuebingen.de
First Name & Middle Initial & Last Name or Official Title & Degree
Alireza Gharabaghi, MD
Phone
0049-7071-29-83550
Email
alireza.gharabaghi@uni-tuebingen.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel Weiss, MD
Organizational Affiliation
University Hospital Tuebingen
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Tübingen
City
Tübingen
ZIP/Postal Code
72076
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daniel Weiss, MD
Phone
49 7071 29 82340
Email
daniel.weiss@uni-tuebingen.de

12. IPD Sharing Statement

Citations:
PubMed Identifier
23757762
Citation
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.
Results Reference
background
PubMed Identifier
27043290
Citation
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.
Results Reference
background
PubMed Identifier
19001482
Citation
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.
Results Reference
background
PubMed Identifier
29089922
Citation
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.
Results Reference
background
PubMed Identifier
28246572
Citation
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.
Results Reference
background
PubMed Identifier
21287187
Citation
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.
Results Reference
background

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Combined Stimulation of STN and SNr for Dysphagia in Parkinson's Disease

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