Rostock International Parkinson's Disease Study (ROPAD)
- Conditions
- Parkinson´s Disease
- Registration Number
- NCT03866603
- Lead Sponsor
- CENTOGENE GmbH Rostock
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 25000
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To investigate the prevalence of genetic etiologies of PD 79 months
- Secondary Outcome Measures
Name Time Method To identify LRRK2-positive PD participants from the primary strata, Establishment of a biomarker in the LRRK2-positive cohort 79 months
Trial Locations
- Locations (107)
Tel Aviv Sourasky Medical Center - TASMC
🇮🇱Tel Aviv, Israel
AOUP Secondo Policlinico Federico II Napoli
🇮🇹Napoli, Italy
Università di Pavia, Dipartimento di Medicina Molecolare
🇮🇹Pavia, Italy
Asmn - Irccs
🇮🇹Reggio Emilia, Italy
I.R.C.C.S. San Raffaele Pisana
🇮🇹Roma, Italy
St. Olav's Hospital
🇳🇴Trondheim, Norway
Neurology Department, Hospital de Santa Maria
🇵🇹Lisbon, Portugal
Centro Hospitalar Universitário de São João
🇵🇹Porto, Portugal
Hospital Universitario de Bellvitge
🇪🇸L'Hospitalet De Llobregat, Barcelona, Spain
Hospital Clinico Universitario Santiago de Compostela
🇪🇸Santiago de Compostela, Corunna, Spain
Hospital Universitario Fundación Alcorcón
🇪🇸Alcorcón, Spain
Instituto Investigacion Biocruces
🇪🇸Barakaldo, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Universitario de La Princesa
🇪🇸Madrid, Spain
Hospital General Unversitario Gregorio Marañón
🇪🇸Madrid, Spain
Hospital Clínico San Carlos
🇪🇸Madrid, Spain
HM CINAC | Integrated Neuroscience Center
🇪🇸Móstoles, Spain
Clinica Universidad de Navarra (CUN)
🇪🇸Pamplona, Spain
Hospital Universitario Donostia
🇪🇸San Sebastián, Spain
University Hospital Marqués de Valdecilla
🇪🇸Santander, Spain
Cukurova University Faculty of Medicine
🇹🇷Sarıçam, Adana, Turkey
Koc University Hospital
🇹🇷Istanbul, Turkey
Istanbul Faculty of Medicine
🇹🇷Istanbul, Turkey
Mersin Faculty of Medicine
🇹🇷Mersin, Turkey
Fairfield General Hospital
🇬🇧Bury, United Kingdom
University of Dundee
🇬🇧Dundee, United Kingdom
University of Edinburgh
🇬🇧Edinburgh, United Kingdom
Royal Devon and Exeter Hospital
🇬🇧Exeter, United Kingdom
Imperial College Healthcare NHS Trust
🇬🇧London, United Kingdom
Newcastle University, Clinical Ageing Research Unit
🇬🇧Newcastle upon Tyne, United Kingdom
WR-CRCN
🇺🇸Las Vegas, Nevada, United States
Tucson Neuroscience Research
🇺🇸Tucson, Arizona, United States
Pharmacology Research Institute
🇺🇸Newport Beach, California, United States
Neuro-Pain Medical Center
🇺🇸Fresno, California, United States
University of California (UC) San Diego
🇺🇸La Jolla, California, United States
Loma Linda University
🇺🇸Loma Linda, California, United States
Parkinson's Disease and Movement Disorder Center of Baco Raton
🇺🇸Baco Raton, Florida, United States
Linfritz Research Institute
🇺🇸Coral Gables, Florida, United States
Renstar Medical Research
🇺🇸Ocala, Florida, United States
University of South Florida
🇺🇸Tampa, Florida, United States
Vero Beach Neurology & Research Institute
🇺🇸Vero Beach, Florida, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Northshore University HealthSystem
🇺🇸Evanston, Illinois, United States
Indiana University, Department of Neurology
🇺🇸Indianapolis, Indiana, United States
Michigan Institute for Neurological Disorders
🇺🇸Farmington Hills, Michigan, United States
Neuroscience Research Institute of NJ
🇺🇸Toms River, New Jersey, United States
Dent Neurologic Institue
🇺🇸Amherst, New York, United States
Stony Brook University School of Medicine
🇺🇸Brookhaven, New York, United States
South Shore Neurologic Associates
🇺🇸Patchogue, New York, United States
Duke University, Department of Neurology
🇺🇸Durham, North Carolina, United States
M3 Wake Research, Inc.
🇺🇸Raleigh, North Carolina, United States
WR-ClinSearch, LLC
🇺🇸Chattanooga, Tennessee, United States
Booth Gardner Parkinson's Care Center
🇺🇸Kirkland, Washington, United States
Inland Northwest Research
🇺🇸Spokane, Washington, United States
Qendra Spitalore University
🇦🇱Tirana, Albania
University Hospital of Antwerp
🇧🇪Antwerp, Belgium
UZ Leuven, Campus Gasthuisberg
🇧🇪Leuven, Belgium
Department of Neurology, Centre Hospitalier Universitaire (CHU) de Leige
🇧🇪Liège, Belgium
AZ Damiaan, Department of Neurology
🇧🇪Oostende, Belgium
Hospital das Clínicas da Universidade Federal de Minas Gerais
🇧🇷Belo Horizonte, Minas Gerais, Brazil
Hospital Ophir Loyola
🇧🇷Belém, Pará, Brazil
Federal University of Health Science of Porto Alegre
🇧🇷Porto Alegre, Rio Grande do Sul, Brazil
Universidade Metropolitana De Santos
🇧🇷Santos, São Paulo, Brazil
Hospital Universitário Walter Cândido/ Universidade Federal do Ceará
🇧🇷Ceará, Brazil
Hospital Angelina Caron
🇧🇷Curitiba, Brazil
Fundação Hospital Adriano Jorge
🇧🇷Manaus, Brazil
Carolina São Souza
🇧🇷Ribeirão Preto, Brazil
Faculdade de Medicina de Ribeirão Preto - USP
🇧🇷Ribeirão Preto, Brazil
Hospital Universitario Pedro Ernesto (HUPE)
🇧🇷Rio De Janeiro, Brazil
Universidade Federal de São Paulo, UNIFESP
🇧🇷São Paulo, Brazil
Clinica de Neurocirurgia E Neurofisiologia Ltda
🇧🇷São Paulo, Brazil
Instituto Israelita de Ensino e Pesquisa Albert Einstein
🇧🇷São Paulo, Brazil
Toronto Western Hospital, University Health Network, University of Toronto
🇨🇦Toronto, Ontario, Canada
Groupe Hospitalier Paris Saint-Joseph
🇫🇷Paris, France
Universitätsklinik für Neurologie
🇩🇪Jena, Germany
Kliniken Beelitz
🇩🇪Beelitz Heilstätten, Germany
Neurologisches Fachkrankenhaus für Bewegungsstörungen / Parkinson
🇩🇪Beelitz, Germany
Charite University Medicine
🇩🇪Berlin, Germany
Gertrudis-Kliniken im Parkison-Zentrum
🇩🇪Biskirchen, Germany
St. Josef-Hospital
🇩🇪Bochum, Germany
Universitätsklinikum Carl Gustav Carus die Dresdner
🇩🇪Dresden, Germany
Universitätsklinik Hamburg-Eppendorf
🇩🇪Hamburg-Eppendorf, Germany
Asklepios Klinik Barmbek
🇩🇪Hamburg, Germany
Paracelsus Elena-Klinik
🇩🇪Kassel, Germany
Universitätsklinikum Schleswig-Holstein, Klinik für Neurologie
🇩🇪Kiel, Germany
Universitätsklinikum Leipzig
🇩🇪Leipzig, Germany
Universitätsklinikum Schleswig-Holstein Campus Lübeck
🇩🇪Luebeck, Germany
Universitätsklinikum Marburg Klinik und Poliklinik für Neurologie Parkinson Netzwerk Allianz Marburg (PANAMA)
🇩🇪Marburg, Germany
Diakonie-Klinikum Schwäbisch Hall gGmbH
🇩🇪Schwäbisch Hall, Germany
Asklepios Fachklinikum Stadtroda Klinik für Neurologie, Schmerztherapie und Schlafmedizin
🇩🇪Stadtroda, Germany
Universitätsklinikum Würzburg
🇩🇪Würzburg, Germany
Mediterraneo Hospital
🇬🇷Athens, Greece
Samson Assuta Ashdod University Hospital
🇮🇱Ashdod, Israel
Barzilai Medical Center
🇮🇱Ashkelon, Israel
Soroka Medical Center
🇮🇱Be'er Sheva, Israel
Shamir Medical Center
🇮🇱Be'er Ya'aqov, Israel
RAMBAM Medical Center
🇮🇱Haifa, Israel
Shaare Zedek Medical Center
🇮🇱Jerusalem, Israel
Hadassah Medical Center
🇮🇱Jerusalem, Israel
Rabin MC, Beilinson Campus
🇮🇱Petach Tikva, Israel
Sheba Medical Center
🇮🇱Ramat Gan, Israel
University of Oxford, Nuffield Department of Clinical Neurosciences
🇬🇧Oxford, United Kingdom
University of Plymouth
🇬🇧Plymouth, United Kingdom
Royal Preston Hospital, Department of Neurology
🇬🇧Preston, United Kingdom
Salford Royal NHS Foundation Trust
🇬🇧Salford, United Kingdom
Royal Cornwall Hospitals Nhs Trust
🇬🇧Truro, United Kingdom
Yeovil District Hospital
🇬🇧Yeovil, United Kingdom