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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT03866603
Other study ID # ROPAD 01-2019
Secondary ID
Status Recruiting
Phase
First received
Last updated
Start date May 30, 2019
Est. completion date December 31, 2025

Study information

Verified date September 2023
Source CENTOGENE GmbH Rostock
Contact ROPAD Clinical Project Manager
Phone +49 381 80113 544
Email sana.iftikhar@centogene.com
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial 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.


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 information / eligibility

Status Recruiting
Enrollment 25000
Est. completion date December 31, 2025
Est. primary completion date December 31, 2025
Accepts healthy volunteers No
Gender All
Age group 30 Years to 80 Years
Eligibility - 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

Study Design


Related Conditions & MeSH terms


Locations

Country Name City State
Albania Qendra Spitalore University Tirana
Belgium 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
Brazil Hospital Ophir Loyola Belém Pará
Brazil Hospital das Clínicas da Universidade Federal de Minas Gerais Belo Horizonte Minas Gerais
Brazil Hospital Universitário Walter Cândido/ Universidade Federal do Ceará Ceará
Brazil Hospital Angelina Caron Curitiba
Brazil Fundação Hospital Adriano Jorge Manaus
Brazil Federal University of Health Science of Porto Alegre Porto Alegre Rio Grande Do Sul
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 Metropolitana De Santos Santos São Paulo
Brazil Clinica de Neurocirurgia E Neurofisiologia Ltda São Paulo
Brazil Instituto Israelita de Ensino e Pesquisa Albert Einstein São Paulo
Brazil Universidade Federal de São Paulo, UNIFESP São Paulo
Canada Toronto Western Hospital, University Health Network, University of Toronto Toronto Ontario
France Groupe Hospitalier Paris Saint-Joseph Paris
Germany Universitätsklinik für Neurologie Aachen
Germany Neurologisches Fachkrankenhaus für Bewegungsstörungen / Parkinson Beelitz
Germany Kliniken Beelitz Beelitz Heilstätten
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 Asklepios Klinik Barmbek Hamburg
Germany Universitätsklinik Hamburg-Eppendorf Hamburg-Eppendorf
Germany Universitätsklinik für Neurologie Jena
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
Greece Mediterraneo Hospital Athens
Israel 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 Hadassah Medical Center Jerusalem
Israel Shaare Zedek Medical Center Jerusalem
Israel Rabin MC, Beilinson Campus Petach Tikva
Israel Sheba Medical Center Ramat Gan
Israel Tel Aviv Sourasky Medical Center - TASMC Tel Aviv
Italy 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
Norway St. Olav's Hospital Trondheim
Portugal Neurology Department, Hospital de Santa Maria Lisbon
Portugal Centro Hospitalar Universitário de São João Porto
Spain Hospital Universitario Fundación Alcorcón Alcorcón
Spain Instituto Investigacion Biocruces Barakaldo
Spain Hospital Universitari Vall d'Hebron Barcelona
Spain Hospital Universitario de Bellvitge L'Hospitalet De Llobregat Barcelona
Spain Hospital Clínico San Carlos Madrid
Spain Hospital General Unversitario Gregorio Marañón Madrid
Spain Hospital Universitario de La Princesa 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 Hospital Clinico Universitario Santiago de Compostela Santiago de Compostela Corunna
Turkey Istanbul Faculty of Medicine Istanbul
Turkey Koc University Hospital Istanbul
Turkey Mersin Faculty of Medicine Mersin
Turkey Cukurova University Faculty of Medicine Sariçam Adana
United Kingdom 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 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 States Dent Neurologic Institue Amherst New York
United States Parkinson's Disease and Movement Disorder Center of Baco Raton Boca Raton Florida
United States Stony Brook University School of Medicine Brookhaven New York
United States WR-ClinSearch, LLC Chattanooga Tennessee
United States Rush University Medical Center Chicago Illinois
United States Linfritz Research Institute Coral Gables Florida
United States Duke University, Department of Neurology Durham North Carolina
United States Pharmacology Research Institute Encino California
United States Northshore University HealthSystem Evanston Illinois
United States Michigan Institute for Neurological Disorders Farmington Hills Michigan
United States Neuro-Pain Medical Center Fresno California
United States Indiana University, Department of Neurology Indianapolis Indiana
United States Booth Gardner Parkinson's Care Center Kirkland Washington
United States University of California (UC) San Diego La Jolla California
United States WR-CRCN Las Vegas Nevada
United States Loma Linda University Loma Linda California
United States Pharmacology Research Institute Los Alamitos California
United States Pharmacology Research Institute Newport Beach California
United States Renstar Medical Research Ocala Florida
United States South Shore Neurologic Associates Patchogue New York
United States M3 Wake Research, Inc. Raleigh North Carolina
United States Inland Northwest Research Spokane Washington
United States University of South Florida Tampa Florida
United States Neuroscience Research Institute of NJ Toms River New Jersey
United States Tucson Neuroscience Research Tucson Arizona
United States Vero Beach Neurology & Research Institute Vero Beach Florida

Sponsors (1)

Lead Sponsor Collaborator
CENTOGENE GmbH Rostock

Countries where clinical trial is conducted

United States,  Albania,  Belgium,  Brazil,  Canada,  France,  Germany,  Greece,  Israel,  Italy,  Norway,  Portugal,  Spain,  Turkey,  United Kingdom, 

References & Publications (1)

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. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary To investigate the prevalence of genetic etiologies of PD 79 months
Secondary To identify LRRK2-positive PD participants from the primary strata, Establishment of a biomarker in the LRRK2-positive cohort 79 months
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