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

May 29, 2018 updated by: Daniel Weiss, University Hospital Tuebingen

Combined Stimulation of Subthalamic Nucleus and Substantia Nigra Pars Reticulata for Dysphagia: A Randomized Controlled Multicenter Trial

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 78 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: [standard STN] + swallowing therapy
standard stimulation on subthalamic (STN) contacts plus swallowing therapy
Device: [standard STN]
standard stimulation on subthalamic (STN) contacts High frequency deep brain stimulation with variable (best individual) stimulation on subthalamic contacts
Other Names:
  • subthalamic deep brain stimulation
Behavioral: Swallowing therapy
Swallowing therapy with speech therapist
Experimental: [STN+SNr] + swallowing therapy
Combined stimulation of the subthalamic nucleus (STN) and the substantia nigra pars reticulata (SNr) plus swallowing therapy
Behavioral: Swallowing therapy
Swallowing therapy with speech therapist
Device: [STN+SNr]
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
Other Names:
  • combined subthalamic and nigral stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Penetration Aspiration Scale
Time Frame: 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
Outcome after eight weeks (V2) with reference to baseline (V1)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
MDS-UPDRS parts I, II, III and IV
Time Frame: Outcome after eight weeks (V2) with reference to baseline (V1)
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
Time Frame: Outcome after eight weeks (V2) with reference to baseline (V1)
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)
Time Frame: Outcome after eight weeks (V2) with reference to baseline (V1)

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
Time Frame: Outcome after eight weeks (V2) with reference to baseline (V1)
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)
Time Frame: Outcome after eight weeks (V2) with reference to baseline (V1)
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
Time Frame: Outcome after eight weeks (V2)
(self-reporting, caregiver-reporting)
Outcome after eight weeks (V2)
Diary on swallowing an related complications
Time Frame: Outcome after eight weeks (V2) with reference to baseline (V1)
complications (cough, suffocation, bronchitis, aspiration pneumonia)
Outcome after eight weeks (V2) with reference to baseline (V1)
Site of Swallow reflex initiation
Time Frame: Outcome after eight weeks (V2) with reference to baseline (V1)
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)
Time Frame: Outcome after eight weeks (V2) with reference to baseline (V1)
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)
Time Frame: Outcome after eight weeks (V2) with reference to baseline (V1)
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)
Time Frame: Outcome after eight weeks (V2) with reference to baseline (V1)
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Tuebingen

Collaborators

Michael J. Fox Foundation for Parkinson's Research

Investigators

  • Principal Investigator: Daniel Weiss, MD, University Hospital Tuebingen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 27, 2018

Primary Completion (Anticipated)

May 1, 2020

Study Completion (Anticipated)

July 1, 2020

Study Registration Dates

First Submitted

December 30, 2017

First Submitted That Met QC Criteria

March 12, 2018

First Posted (Actual)

March 19, 2018

Study Record Updates

Last Update Posted (Actual)

May 30, 2018

Last Update Submitted That Met QC Criteria

May 29, 2018

Last Verified

May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 686/2017BO1

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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