Rostock International Parkinson's Disease Study (ROPAD)

Active, not recruiting

• 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.

Study Timeline

• Study First Submitted: 2019-03-01
• Study First Submitted QC: 2019-03-06
• Study First Posted: 2019-03-07
• Study Start: 2019-05-30
• Status Verified: 2023-09
• Last Update Submitted: 2024-07-01
• Last Update Posted: 2024-07-03
• Primary Completion: 2025-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 25000

Inclusion Criteria

Not provided

Exclusion Criteria

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)

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

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