Systematic Assessment of Laryngopharyngeal Function in Patients With MSA, PD, and 4repeat Tauopathies

Parkinson Disease Clinical Trial

— FEEMSA  

Official title:

Prospective Observational Study for the Systematic Assessment of Laryngopharyngeal Function in Patients With Multiple System Atrophy, Parkinson's Disease and 4repeat Tauopathies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04706234
• Other study ID #: S21(a)/2017
• Status: Recruiting
• Start date: September 1, 2017
• Est. completion date: July 31, 2024

Study information

• Verified date: June 2023
• Source: Kliniken Beelitz GmbH
• Contact: Florin Gandor, MD
• Phone: +493320422781
• Email: gandor[@]kliniken-beelitz.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is a non-interventional observational study designed to systematically record the results of routine laryngeal examinations and specific characteristics of dysphagia in patients with multiple system atrophy (MSA), Parkinson's disease (PD) and progressive supranuclear palsy (PSP) and related 4repeat tauopathies. The results of a fiberoptic / flexible endoscopic evaluation of swallowing (FEES) while performing a structured task protocol will be recorded. If available, laryngeal electromyography (EMG) results will also be recorded. In addition to the examination results, demographic and disease-specific data are collected, and two questionnaires, the Swallowing Disturbance Questionnaire for Parkinson's Disease (SDQ-PD) and the swallowing specific Quality Of Life Questionnaire (SWALQOL), are administered.

Description:

Multiple system atrophy (MSA) is a sporadic progressive neurodegenerative disorder caused by oligodendroglial aggregation of α-synuclein affecting predominantly the nigrostriatal, olivo-ponto-cerebellar, and autonomic systems,resulting in a clinical presentation of dysautonomia combined with either predominantly parkinsonian (MSA-P) or cerebellar (MSA-C) symptoms of varying severity.In its early stage, the diagnosis of MSA according to the second consensus criteria can be challenging. Therefore, the Movement Disorders Society MSA study group recently addressed the importance of developing valuable diagnostic tools for securing an early diagnosis in patients with MSA not only to estimate disease prognosis but also to early initiate novel, potentially disease-modifying treatments in clinical trials. Despite laryngopharyngeal dysfunction being associated with decreased life expectancy and quality of life, systematic assessment of these functions in MSA is scarce. Previously, an easy-to-implement MSA-FEES task-protocol was suggested to systematically assess laryngopharyngeal function.

A pilot study on 8 patients with MSA not only showed that the task protocol was feasible and well tolerated, but also that laryngopharyngeal symptoms where highly prevalent despite the lack of clinical presentation (Warnecke et. al 2019). Moreover, irregular arytenoid cartilages movements where present in all MSA-patients when performing this task protocol, suggesting this symptom could serve as a clinical marker to identify MSA-patients.

Following this pilot study, an observational two center study assessed 57 MSA patients with this protocol and compared findings to an age-matched cohort of PD-patients (Gandor et al. 2020). While only 43.9% of MSA patients had clinical symptoms of laryngeal dysfunction, 93% showed laryngeal abnormalities during FEES performing the task-protocol. 91.2% of MSA-patients showed irregular arytenoid cartilages movements. In contrast, only one PD patient showed laryngeal abnormalities with vocal fold motion impairment, but not irregular arytenoid cartilages movements. This study suggests that irregular arytenoid cartilages movements allow differentiating MSA from PD with a sensitivity of 0.9 and a specificity of 1.0.

The aim of this FEEMSA trial is to continue recruitment of patients with MSA and PD and systematically assess laryngopharyngeal function in an even larger cohort. Moreover, patients with PSP and related 4repeat tauopathies will also be recruited at eligible sites to compare results from this cohort to results in MSA and PD. If available, laryngeal EMG will also be recorded.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: July 31, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• diagnosis of probable or possible multiple system atrophy according to current consensus criteria (Gilman et al. 2008) or

• diagnosis of probable or possible PSP according to the the Movement Disorders Society (MDS) diagnostic criteria (Höglinger et al. 2017) or

• diagnosis of Parkinson's disease according to the MDS diagnostic criteria (Postuma et al 2015)

• Hoehn and Yahr Stage within the range of I-V

Exclusion Criteria:

• Patients who do not sign the consent form

• Patients who have contraindications for performing fiber endoscopic laryngoscopy and swallowing examination.

• Pregnancy in female patients

Related Conditions & MeSH terms

• Atrophy
• Multiple System Atrophy
• Parkinson Disease
• Progressive Supranuclear Palsy
• Shy-Drager Syndrome
• Supranuclear Palsy, Progressive
• Tauopathies

Locations

Country	Name	City	State
Austria	Department of Neurology and Department of ENT, Medical University Innsbruck	Innsbruck	Tirol
Germany	Movement Disorders Hospital - Kliniken Beelitz	Beelitz-Heilstätten	Brandenburg
Germany	Department of Neurology, University Hospital Carl Gustav Carus	Dresden	Sachsen
Germany	Asklepios Klinik Barmbek	Hamburg
Germany	Department of Neurology Asklepios Klinik Barmbek	Hamburg
Germany	Department of Neurology, Medical School Hannover	Hannover	Niedersachsen
Germany	Department of Neurology, University Hospital Münster	Münster	Nordrhein-Westfalen
Germany	Asklepios Fachklinikum Stadtroda	Stadtroda	Thuringia
Germany	Department of Neueology Asklepios Klinik Stadtroda	Stadtroda	Thuringia
Germany	Department of Neurology, Medical University of Ulm	Ulm	Baden-Württemberg
Israel	Department of Neurology, Movement Disorders Unit, Medical Center Tel Aviv	Tel Aviv
Italy	IRCCS Istituto delle Scienze Neurologiche, Azienda USL di Bologna	Bologna
Japan	Department of Neurology, Gifu University Graduate School of Medicine	Gifu
Korea, Republic of	Department of Neurology SNUCM	Seoul
Poland	Department of Neurology, Medical University Warsaw	Warsaw
Spain	Unidad de Parkinson y Trastornos del Movimiento Instituto Clínic de Neurociencias, Hospital Clinic de Barcelona	Barcelona	Catalonia

Sponsors (8)

Lead Sponsor	Collaborator
Kliniken Beelitz GmbH	Hannover Medical School, Medical University Innsbruck, Medical University of Warsaw, University Hospital Carl Gustav Carus, University Hospital Muenster, University of Barcelona, University of Ulm

Countries where clinical trial is conducted

Austria,  Germany,  Israel,  Italy,  Japan,  Korea, Republic of,  Poland,  Spain, 

References & Publications (3)

Gandor F, Vogel A, Claus I, Ahring S, Gruber D, Heinze HJ, Dziewas R, Ebersbach G, Warnecke T. Laryngeal Movement Disorders in Multiple System Atrophy: A Diagnostic Biomarker? Mov Disord. 2020 Dec;35(12):2174-2183. doi: 10.1002/mds.28220. Epub 2020 Aug 5. — View Citation

Vogel A, Claus I, Ahring S, Gruber D, Haghikia A, Frank U, Dziewas R, Ebersbach G, Gandor F, Warnecke T. Endoscopic Characteristics of Dysphagia in Multiple System Atrophy Compared to Parkinson's Disease. Mov Disord. 2022 Mar;37(3):535-544. doi: 10.1002/mds.28854. Epub 2021 Nov 13. — View Citation

Warnecke T, Vogel A, Ahring S, Gruber D, Heinze HJ, Dziewas R, Ebersbach G, Gandor F. The Shaking Palsy of the Larynx-Potential Biomarker for Multiple System Atrophy: A Pilot Study and Literature Review. Front Neurol. 2019 Mar 26;10:241. doi: 10.3389/fneur.2019.00241. eCollection 2019. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	laryngeal EMG findings	abnormalities recorded on laryngeal EMG showing denervation, dystonic co-activation or myoclonic discharges	1 day
Primary	laryngeal movement disorders	occurrence of vocal fold motion impairment, paradoxical vocal fold motion, vocal fold fixation or involuntary irregular arytenoid cartilages movements when assessed with the task-protocol	1 day
Primary	dysphagia	occurrence of dysphagic symptoms when assessed with the task-protocol	1 day