Brief Summary

Parkinson's disease (PD) is the second most common neurodegenerative disease, which affects 2-3% of the general population above 65 years. There are significant differences in incidence depending on geographical location, race, and ethnicity. The exact cause of the disease is still unknown, but the role of genetic and environmental factors has already been established. Certain genetic forms of the disease make up for a small percentage, so it is thought that environmental factors have a more significant impact on the development of the disease. The incidence of PD is higher in people exposed to significant quantities of pesticides and traumatic brain injury, while there is a smaller incidence in smokers and people consuming more significant quantities of caffeine. The project will finish in four years, with the first 20 months dedicated to the first phase (genetic-epidemiological research), and the entirety of the 48 months for the second phase of the project (prospective clinical research). The main goal of the first phase of the project is to determine which genetic mutations are the ones most represented in the Croatian population afflicted with the familial form of PD. In the second phase the main goal is to determine the influence of genetic factors and microbiological factors on the disease's progression as well as on the treatment outcomes. Specific goals of this part of the project are to determine how many patients in the general population of PD patients present with a genetic disorder and which genes have a role in that disorder, as well as determine the composition of intestinal and oral microbiota both in the patient test group and the healthy control group. Furthermore, specific goals are to evaluate the effects of standard PD treatment on the composition of microbiota, neurodegeneration progression and the activity of neuroinflammation in the central nervous system (CNS) and to examine whether there is a link between the physiological and the pathophysiological function of microbiota, using markers of disease progression and glial activity. Last specific goal is to analyze potential pathological conformation protein forms that could be used as a biomarker in early stages of the disease and a biomarker of disease progression. The first phase of the study will provide the first epidemiologic data on the familial form of PD, as well as the mutations most represented in patients with PD in Croatia. Additionally, the prospective clinical study will contribute to enlightening the intertwined effects of genetic and environmental factors in the emergence and progression of the disease, as well as their effect on treatment outcome. Intestinal and oral microbiota composition analysis will determine whether there is a difference between PD and the healthy population while using the short-chain fatty acid profile will determine the metabolic differences between the two groups. Analyzing the markers of CNS homeostasis, inflammation, and neuroglial function will determine the progression of the disease and also correlate them to genetic factors as well as the microbiota function and composition. Analyzing the pathological conformation forms of alpha-synuclein could lead to the discovery of novel biomarkers in the early stages of the disease, as well as to follow the progression of the disease

Trial Health

At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date

Enrollment

300

participants targeted

Target at P75+ for all trials

Timeline

Completed

Started May 2020

Typical duration for all trials

Geographic Reach

1 country

1 active site

Status

unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

3.8 years study duration

Study Start

First participant enrolled

May 1, 2020

Completed

1.3 years until next milestone

First Submitted

Initial submission to the registry

August 4, 2021

Completed

13 days until next milestone

First Posted

Study publicly available on registry

August 17, 2021

Completed

2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2023

Completed

6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2024

Completed

Last Updated

August 17, 2021

Status Verified

August 1, 2021

Enrollment Period

3.3 years

First QC Date

August 4, 2021

Last Update Submit

August 9, 2021

Conditions

Parkinson Disease Genetic Disease Microbiota Neuro-Degenerative Disease Neuroinflammatory Response

Keywords

Parkinson's diseaseGenetics of Parkinson's diseaseMicrobiotaMicroglia

Outcome Measures

Primary Outcomes (3)

Genetic mutations in familial or early onset Croatian Parkinson's disease patients
Determining which genetic mutations are the ones most represented in the Croatian population afflicted with the familiar or early onset form of PD.
20 months
Influence of genetic factors on the disease's progression and treatment outcomes.
Determining the influence of genetic factors on the disease's progression and treatment outcomes.
48 months
Influence of microbiological factors on the disease's progression and treatment outcomes.
Determining the influence of microbiological factors on the disease's progression and treatment outcomes.
48 months

Secondary Outcomes (5)

Genetic factors in general Croatian Parkinson's disease patients
48 months
Composition of microbiota in Croatian PD patients and controls
48 months
Effects of Parkinson's disease treatment on microbiota and inflammatory response in Parkinson's disease patients
48 months
Influence of microbiota and inflammatory factors on progression and treatment in Croatian PD patients
48 months
Pathological alpha-synuclein conformation in PD patients and controls
48 months.

Study Arms (3)

Genetic testing cohort (Phase 1)

Group of Croatian Parkinson's disease patients who will be tested with whole-exome sequencing in target Parkinson's genes.

Diagnostic Test: Whole-exome sequencing

Drug-naive Parkinson's disease patients (Phase 2)

Drug-naive Parkinson's disease patients that will be prospectively followed in the two-year period for each patient.

Diagnostic Test: Whole-exome sequencingDiagnostic Test: Microbiota sequencingDiagnostic Test: Magnetic resonance imagingDiagnostic Test: Transcranial ultrasound and ElectroencephalographyDiagnostic Test: ELISA (Enzyme-Linked Immunosorbent Assay)Diagnostic Test: Fluorescent correlation spectroscopy (FCS)

Control group (Phase 2)

Control patients who do not have neurodegenerative diseases. The control group will perform the same measurement as the drug-naive Parkinson's disease patients.

Interventions

Whole-exome sequencingDIAGNOSTIC_TEST

Whole-exome sequencing with the focus on Parkinson's disease loci.

Control group (Phase 2)Drug-naive Parkinson's disease patients (Phase 2)Genetic testing cohort (Phase 1)

Microbiota sequencingDIAGNOSTIC_TEST

Next generation sequencing of microbiota from stool and saliva samples.