Clinical trial NCT03866603: Rostock International Parkinson's Disease Study (ROPAD)
Official title: Rostock International Parkinson's Disease Study: an International, Multicenter, Epidemiological Observational Study
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Parkinson´s Disease
Keywords: Parkinson´s disease
Biomarker
LRRK2
GBA
PD Genetics
Lead sponsor: CENTOGENE GmbH Rostock
Sponsor class: INDUSTRY
First posted: 2019-03-07
Enrollment: 25000
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants clinically diagnosed with Parkinson's Disease (PD)

Brief summary: Rostock International Parkinson's Disease Study - An International, multicenter, epidemiological observational study aiming at identification of LRRK2-positive patients, the recruitment of 25,000 PD participants and the establishment of a candidate biomarker in the LRRK2-positive cohort.

Detailed description: Parkinson's disease (PD) is one of the most common neurodegenerative disorders worldwide, affecting approximately 1% of individuals older than 60 years and causes progressive disability.

Clinical signs and symptoms of PD include the following: asymmetric tremor at rest, bradykinesia, muscle rigidity, postural instability, gait abnormalities including festination and freezing. Onset is typically after the age of 50 years and the disease is commonly slowly progressive. The most common initial finding of PD is a resting tremor in the upper extremity. Over time, participants experience progressive bradykinesia, rigidity, and gait difficulty, while the axial posture becomes progressively flexed. Non-motor symptoms are common in all stages of Parkinson disease and they include constipation, seborrhea, hyposmia or anosmia, sympathetic denervation of the heart, depression and/or apathy, sleep disturbances, cognitive decline and dementia. They may appear prior to the movement disorder and can be used as preclinical markers of PD.

PD is mostly considered as idiopathic disease; however more and more data suggest that it is a disease that involves interaction of genetic and environmental factors. The most common monogenic form and the one most closely resembling idiopathic PD is LRRK2 (Leucine-rich repeat kinase 2 gene) associated PD.

The most common monogenic form and the one most closely resembling idiopathic PD is LRRK2 (Leucine-rich repeat kinase 2 gene) associated PD. First identified in 2004, LRRK2 mutations are currently still the most commonly known cause of PD and account for up to \~40% of all Parkinson's disease cases in select populations. The majority of reported LRRK2-positive PD patients are Caucasian (63%), whereas all other ethnicities comprise \~10% or fewer patients of described mutation carriers despite clusters in the Ashkenazi Jewish and Arab Berber populations. With respect to country of origin, the majority of patients were re-ported to reside in Italy or Spain (14% each), Great Britain (10%) or Norway (9%). Definitely pathogenic variants identified in LRRK2 include p.G2019S, p.R1441C/G/H, p.N1437H, p.Y1699C, and, p.I2020T. Of these, the p.R1441G mutation is particularly frequent, as it represents a founder mutation in the Basque population where it is responsible for 46% of all familial PD. Very rarely, this mutation has also been observed in other populations where it arose on a different haplotype. LRRK2 p.Gly2019Ser mutation accounts for about 0.5% simplex cases and \>5% familial cases in various ethnic groups worldwide. Furthermore, genome-wide association studies have identified common polymorphisms in LRRK2 that associate with idiopathic PD, implicating LRRK2 function in susceptibility to late-onset PD in individuals without pathogenic mutations.

LRRK2 mutations cause PD with age-related penetrance and clinical features identical to late-onset sporadic PD. Biochemical studies support an increase in LRRK2 kinase activity and a decrease in GTPase activity for kinase domain and Roc-COR mutations, respectively. Strong evidence exists that LRRK2 toxicity is kinase dependent, leading to extensive efforts to identify selective and brain-permeable LRRK2 kinase inhibitors for clinical development. LRRK2 kinase inhibition is currently one of the most prevailing disease-modifying therapeutic strategies for PD. Thus, LRRK2 kinase inhibitors are in development as potential Parkinson's disease therapeutics.

Furthermore, there is now evidence showing that LRRK2 expression and phosphorylation levels have a potential as markers of Parkinson's disease. Recently, the presence of Lrrk2 was confirmed in exosomes from human biofluids, including urine and cerebrospinal fluid. Moreover, elevated LRRK2 autophosphorylation was identified in brain-derived and peripheral exosomes in LRRK2-mutation carriers. In summary, it has been shown that markers of LRRK2 activity and function may be detected in human blood and that they are relevant for pathogenesis if PD.

Thus, the biochemical analyses of human blood from LRRK2 positive participants and LRRK2 negative participants create a strong base for the development of PD-related biomarkers. This biomarker may in turn be even more accessible than genetic testing and it may serve for diagnosis, prognosis, and prediction of PD.

Eligibility criteria: * Informed consent is obtained from the participant
* The participant has been clinically diagnosed with Parkinson's disease within the last 5 years (≤ 5 years)
* The participant is between 30 and 80 years old

Primary outcomes:
measure: To investigate the prevalence of genetic etiologies of PD
timeFrame: 79 months
Secondary outcomes:
measure: To identify LRRK2-positive PD participants from the primary strata, Establishment of a biomarker in the LRRK2-positive cohort
timeFrame: 79 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Tucson Neuroscience Research
state: Arizona
city: Encino
country: United States
facility: Pharmacology Research Institute
state: California
city: Fresno
country: United States
facility: Neuro-Pain Medical Center
state: California
city: La Jolla
country: United States
facility: University of California (UC) San Diego
state: California
city: Loma Linda
country: United States
facility: Loma Linda University
state: California
city: Los Alamitos
country: United States
facility: Pharmacology Research Institute
state: California
city: Newport Beach
country: United States
facility: Pharmacology Research Institute
state: California
city: Baco Raton
country: United States
facility: Parkinson's Disease and Movement Disorder Center of Baco Raton
state: Florida
city: Coral Gables
country: United States
facility: Linfritz Research Institute
state: Florida
city: Ocala
country: United States
facility: Renstar Medical Research
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Vero Beach
country: United States
facility: Vero Beach Neurology & Research Institute
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Evanston
country: United States
facility: Northshore University HealthSystem
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University, Department of Neurology
state: Indiana
city: Farmington Hills
country: United States
facility: Michigan Institute for Neurological Disorders
state: Michigan
city: Las Vegas
country: United States
facility: WR-CRCN
state: Nevada
city: Toms River
country: United States
facility: Neuroscience Research Institute of NJ
state: New Jersey
city: Amherst
country: United States
facility: Dent Neurologic Institue
state: New York
city: Brookhaven
country: United States
facility: Stony Brook University School of Medicine
state: New York
city: Patchogue
country: United States
facility: South Shore Neurologic Associates
state: New York
city: Durham
country: United States
facility: Duke University, Department of Neurology
state: North Carolina
city: Raleigh
country: United States
facility: M3 Wake Research, Inc.
state: North Carolina
city: Chattanooga
country: United States
facility: WR-ClinSearch, LLC
state: Tennessee
city: Kirkland
country: United States
facility: Booth Gardner Parkinson's Care Center
state: Washington
city: Spokane
country: United States
facility: Inland Northwest Research
state: Washington
city: Tirana
country: Albania
facility: Qendra Spitalore University
city: Antwerp
country: Belgium
facility: University Hospital of Antwerp
city: Leuven
country: Belgium
facility: UZ Leuven, Campus Gasthuisberg
city: Liège
country: Belgium
facility: Department of Neurology, Centre Hospitalier Universitaire (CHU) de Leige
city: Oostende
country: Belgium
facility: AZ Damiaan, Department of Neurology
city: Belo Horizonte
country: Brazil
facility: Hospital das Clínicas da Universidade Federal de Minas Gerais
state: Minas Gerais
city: Belém
country: Brazil
facility: Hospital Ophir Loyola
state: Pará
city: Porto Alegre
country: Brazil
facility: Federal University of Health Science of Porto Alegre
state: Rio Grande do Sul
city: Santos
country: Brazil
facility: Universidade Metropolitana De Santos
state: São Paulo
city: Ceará
country: Brazil
facility: Hospital Universitário Walter Cândido/ Universidade Federal do Ceará
city: Curitiba
country: Brazil
facility: Hospital Angelina Caron
city: Manaus
country: Brazil
facility: Fundação Hospital Adriano Jorge
city: Ribeirão Preto
country: Brazil
facility: Carolina São Souza
city: Ribeirão Preto
country: Brazil
facility: Faculdade de Medicina de Ribeirão Preto - USP
city: Rio De Janeiro
country: Brazil
facility: Hospital Universitario Pedro Ernesto (HUPE)
city: São Paulo
country: Brazil
facility: Universidade Federal de São Paulo, UNIFESP
city: São Paulo
country: Brazil
facility: Clinica de Neurocirurgia E Neurofisiologia Ltda
city: São Paulo
country: Brazil
facility: Instituto Israelita de Ensino e Pesquisa Albert Einstein
city: Toronto
country: Canada
facility: Toronto Western Hospital, University Health Network, University of Toronto
state: Ontario
city: Paris
country: France
facility: Groupe Hospitalier Paris Saint-Joseph
city: Aachen
country: Germany
facility: Universitätsklinik für Neurologie
city: Beelitz Heilstätten
country: Germany
facility: Kliniken Beelitz
city: Beelitz
country: Germany
facility: Neurologisches Fachkrankenhaus für Bewegungsstörungen / Parkinson
city: Berlin
country: Germany
facility: Charite University Medicine
city: Biskirchen
country: Germany
facility: Gertrudis-Kliniken im Parkison-Zentrum
city: Bochum
country: Germany
facility: St. Josef-Hospital
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus die Dresdner
city: Hamburg-Eppendorf
country: Germany
facility: Universitätsklinik Hamburg-Eppendorf
city: Hamburg
country: Germany
facility: Asklepios Klinik Barmbek
city: Jena
country: Germany
facility: Universitätsklinik für Neurologie
city: Kassel
country: Germany
facility: Paracelsus Elena-Klinik
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein, Klinik für Neurologie
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
city: Luebeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein Campus Lübeck
city: Marburg
country: Germany
facility: Universitätsklinikum Marburg Klinik und Poliklinik für Neurologie Parkinson Netzwerk Allianz Marburg (PANAMA)
city: Schwäbisch Hall
country: Germany
facility: Diakonie-Klinikum Schwäbisch Hall gGmbH
city: Stadtroda
country: Germany
facility: Asklepios Fachklinikum Stadtroda Klinik für Neurologie, Schmerztherapie und Schlafmedizin
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg
city: Athens
country: Greece
facility: Mediterraneo Hospital
city: Ashdod
country: Israel
facility: Samson Assuta Ashdod University Hospital
city: Ashkelon
country: Israel
facility: Barzilai Medical Center
city: Be'er Sheva
country: Israel
facility: Soroka Medical Center
city: Be'er Ya'aqov
country: Israel
facility: Shamir Medical Center
city: Haifa
country: Israel
facility: RAMBAM Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Petach Tikva
country: Israel
facility: Rabin MC, Beilinson Campus
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center - TASMC
city: Napoli
country: Italy
facility: AOUP Secondo Policlinico Federico II Napoli
city: Pavia
country: Italy
facility: Università di Pavia, Dipartimento di Medicina Molecolare
city: Reggio Emilia
country: Italy
facility: Asmn - Irccs
city: Roma
country: Italy
facility: I.R.C.C.S. San Raffaele Pisana
city: Trondheim
country: Norway
facility: St. Olav's Hospital
city: Lisbon
country: Portugal
facility: Neurology Department, Hospital de Santa Maria
city: Porto
country: Portugal
facility: Centro Hospitalar Universitário de São João
city: L'Hospitalet De Llobregat
country: Spain
facility: Hospital Universitario de Bellvitge
state: Barcelona
city: Santiago de Compostela
country: Spain
facility: Hospital Clinico Universitario Santiago de Compostela
state: Corunna
city: Alcorcón
country: Spain
facility: Hospital Universitario Fundación Alcorcón
city: Barakaldo
country: Spain
facility: Instituto Investigacion Biocruces
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario de La Princesa
city: Madrid
country: Spain
facility: Hospital General Unversitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Móstoles
country: Spain
facility: HM CINAC | Integrated Neuroscience Center
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra (CUN)
city: San Sebastián
country: Spain
facility: Hospital Universitario Donostia
city: Santander
country: Spain
facility: University Hospital Marqués de Valdecilla
city: Sarıçam
country: Turkey
facility: Cukurova University Faculty of Medicine
state: Adana
city: Istanbul
country: Turkey
facility: Koc University Hospital
city: Istanbul
country: Turkey
facility: Istanbul Faculty of Medicine
city: Mersin
country: Turkey
facility: Mersin Faculty of Medicine
city: Bury
country: United Kingdom
facility: Fairfield General Hospital
city: Dundee
country: United Kingdom
facility: University of Dundee
city: Edinburgh
country: United Kingdom
facility: University of Edinburgh
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: Newcastle upon Tyne
country: United Kingdom
facility: Newcastle University, Clinical Ageing Research Unit
city: Oxford
country: United Kingdom
facility: University of Oxford, Nuffield Department of Clinical Neurosciences
city: Plymouth
country: United Kingdom
facility: University of Plymouth
city: Preston
country: United Kingdom
facility: Royal Preston Hospital, Department of Neurology
city: Salford
country: United Kingdom
facility: Salford Royal NHS Foundation Trust
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospitals Nhs Trust
city: Yeovil
country: United Kingdom
facility: Yeovil District Hospital
Study officials:
affiliation: CENTOGENE GmbH
name: Peter Bauer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Baumann CR. Epidemiology, diagnosis and differential diagnosis in Parkinson's disease tremor. Parkinsonism Relat Disord. 2012 Jan;18 Suppl 1:S90-2. doi: 10.1016/S1353-8020(11)70029-3.