Rostock International Parkinson's Disease Study (ROPAD)

Parkinson´s Disease Clinical Trial

— ROPAD  

Official title:

Rostock International Parkinson's Disease Study: an International, Multicenter, Epidemiological Observational Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03866603
• Other study ID #: ROPAD 01-2019
• Status: Recruiting
• 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
• 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

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson´s Disease

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