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

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ClinicalTrials.gov Identifier: NCT03470324
Recruitment Status : Recruiting
First Posted : March 19, 2018
Last Update Posted : May 30, 2018
Sponsor:
Collaborator:
Michael J. Fox Foundation for Parkinson's Research
Information provided by (Responsible Party):
Daniel Weiss, University Hospital Tuebingen

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.

Condition or disease Intervention/treatment Phase
Parkinson's Disease Dysphagia Device: [standard STN] Device: [STN+SNr] Behavioral: Swallowing therapy Not Applicable

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  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Combined Stimulation of Subthalamic Nucleus and Substantia Nigra Pars Reticulata for Dysphagia: A Randomized Controlled Multicenter Trial
Actual Study Start Date : April 27, 2018
Estimated Primary Completion Date : May 1, 2020
Estimated Study Completion Date : July 1, 2020

Resource links provided by the National Library of Medicine


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 Name: 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
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 Name: combined subthalamic and nigral stimulation

Behavioral: Swallowing therapy
Swallowing therapy with speech therapist




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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)


  4. 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.

  5. 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

  6. Clinical global impression self [ Time Frame: Outcome after eight weeks (V2) ]
    (self-reporting, caregiver-reporting)

  7. Diary on swallowing an related complications [ Time Frame: Outcome after eight weeks (V2) with reference to baseline (V1) ]
    complications (cough, suffocation, bronchitis, aspiration pneumonia)

  8. 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)

  9. 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.

  10. 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

  11. 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)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03470324


Contacts
Contact: Daniel Weiss, MD 0049-7071-29-82340 daniel.weiss@uni-tuebingen.de
Contact: Alireza Gharabaghi, MD 0049-7071-29-83550 alireza.gharabaghi@uni-tuebingen.de

Locations
Germany
University of Tübingen Recruiting
Tübingen, Germany, 72076
Contact: Daniel Weiss, MD    49 7071 29 82340    daniel.weiss@uni-tuebingen.de   
Sponsors and Collaborators
University Hospital Tuebingen
Michael J. Fox Foundation for Parkinson's Research
Investigators
Principal Investigator: Daniel Weiss, MD University Hospital Tuebingen

Publications:

Responsible Party: Daniel Weiss, Clinical Professor, University Hospital Tuebingen
ClinicalTrials.gov Identifier: NCT03470324     History of Changes
Other Study ID Numbers: 686/2017BO1
First Posted: March 19, 2018    Key Record Dates
Last Update Posted: May 30, 2018
Last Verified: May 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Daniel Weiss, University Hospital Tuebingen:
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

Additional relevant MeSH terms:
Parkinson Disease
Deglutition Disorders
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Pharyngeal Diseases
Otorhinolaryngologic Diseases