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

NCT ID: NCT03470324

Last Updated: 2018-05-30

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-27
• Study Completion Date: 2020-07-01

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.

Conditions

Parkinson's Disease; Dysphagia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

[standard STN] + swallowing therapy

standard stimulation on subthalamic (STN) contacts plus swallowing therapy

Group Type: ACTIVE_COMPARATOR

[standard STN]

Intervention Type: DEVICE

standard stimulation on subthalamic (STN) contacts High frequency deep brain stimulation with variable (best individual) stimulation on subthalamic contacts

Swallowing therapy

Intervention Type: BEHAVIORAL

Swallowing therapy with speech therapist

[STN+SNr] + swallowing therapy

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

Group Type: EXPERIMENTAL

[STN+SNr]

Intervention Type: 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

Intervention Type: BEHAVIORAL

Swallowing therapy with speech therapist

Interventions

[standard STN]

standard stimulation on subthalamic (STN) contacts High frequency deep brain stimulation with variable (best individual) stimulation on subthalamic contacts

Intervention Type: 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

Intervention Type: DEVICE

Swallowing therapy

Swallowing therapy with speech therapist

Intervention Type: BEHAVIORAL

Other Intervention Names

subthalamic deep brain stimulation; combined subthalamic and nigral stimulation

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Michael J. Fox Foundation for Parkinson's Research

OTHER

Sponsor Role: collaborator

University Hospital Tuebingen

OTHER

Sponsor Role: lead

Responsible Party

Daniel Weiss

Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Daniel Weiss, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital Tuebingen

Locations

University of Tübingen

Tübingen, , Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Daniel Weiss, MD

Role: CONTACT

daniel.weiss@uni-tuebingen.de

0049-7071-29-82340

Alireza Gharabaghi, MD

Role: CONTACT

alireza.gharabaghi@uni-tuebingen.de

0049-7071-29-83550

Facility Contacts

Daniel Weiss, MD

Role: primary

daniel.weiss@uni-tuebingen.de

49 7071 29 82340

References

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.

Reference Type: BACKGROUND

PMID: 23757762 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27043290 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19001482 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29089922 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28246572 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21287187 (View on PubMed)

Other Identifiers

686/2017BO1

Identifier Type: -

Identifier Source: org_study_id