Analysis of the Prognostic Role of Epigenetic Biomarkers in Relation to the Motor Decline in Parkinson's Disease

Parkinson Disease Clinical Trial

— BioGenPark  

Official title:

Analysis of the Prognostic Role of Epigenetic Biomarkers in Relation to the Motor Decline in Parkinson's Disease

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05384522
• Other study ID #: INRCA_002_2022
• Status: Not yet recruiting
• Start date: May 30, 2024
• Est. completion date: January 30, 2026

Study information

• Verified date: October 2023
• Source: Istituto Nazionale di Ricovero e Cura per Anziani
• Contact: Anna Rita Bonfigli
• Phone: +390718003719
• Email: a.bonfigli[@]inrca.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

BioGenParkinson is an observational, prospective cohort study evaluating biomarkers of Parkinson's Disease (PD) progression in community-dwelling subjects aged 65 years or more, consecutively referring to INRCA outpatient clinic of the Neurology Unit. Selected patients will undergo clinical and laboratory evaluations at the baseline, and will be followed up after 6 and 12 months. The biological evaluation will include the determination of i) routine biological parameters ii) advanced biomarkers such as epigenetic analysis of DNA methylation, genetic analysis on multiple loci associated with PD progression and specific proteins associated with motor and non-motor decline. After obtaining all data, multiple statistical analysis will be performed to evaluate the most accurate prognostic biomarkers of PD progression at this stage of disease.

Description:

The objective of the BioGenParkinson study is the evaluation of the prognostic accuracy of epigenetic, genetic and protein biomarkers in relation to Parkinson's Disease (PD) motor symptoms progression (assessed by changes in Unified Parkinson's Disease Rating Scale Part III (UPDRS III)) in biological samples of 103 PD patients aged 65 or more. Changes of quality of life (assessed by Parkinson's Disease Questionnaire 39 item (PDQ-39)) and cognitive performance (assessed by the Mini-Mental State Examination (MMSE)) will be also investigated. The characterization of the PD patients' phenotypes and genotypes will allow the investigation on the predisposition to a severe progression of the disease, in order to early predict the progression of the disease and improving the accuracy of personalized interventions. The evidence collected will inform multidisciplinary and personalized interventions in the future.

Among the advanced biomarkers that will be evaluated in the Study, epigenetic analysis of CpG loci such as cg17445913 in KCNB1 gene, cg02920897 in DLEU2 gene and cg01754178 in PTPRN2 gene are expected to improve the prognostic accuracy of motor and cognitive decline of PD patients at Hoehn and Yahr stage II/III after 12 months of follow up. Genetic analysis in purified genomic DNA samples will be performed on multiple loci associated with PD progression such as rs2230288 and rs75548401 in order to confirm their association with motor decline over time, and to assess their association with non-motor decline.

Protein analysis on bone sialoprotein (BSP), osteomodulin (OMD), aminoacylase-1 (ACY1), and growth hormone receptor (GHR) will be also evaluated with respect to motor and non-motor decline in PD patients in order to be compared with the other biomarkers. Scores on UPDRS Parts III, obtained by using using the published cut-offs classification of MDS-UPDRS severity, will be drawn at the baseline, at 6-month and at 12-month follow-up visits, in order to assess PD motor progression. Additional assessments include demographic and clinical data, Parkinson Disease Questionnaire 39 item (PDQ-39) Hoehn and Yahr stage, MMSE, Frontal Assessment Battery (FAB), list of disease and medication, falls, functional status, quality of life and socio-economic characteristics.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 103
• Est. completion date: January 30, 2026
• Est. primary completion date: January 30, 2026
• Gender: All
• Age group: 65 Years and older

Eligibility

Inclusion Criteria:

• PD at Hoehn and Yahr stage =3

• MMSE test =24 score

Exclusion Criteria:

• MMSE score < 24

• Severe cardiovascular diseases (including congestive heart failure NYHA=4, acute coronary syndrome, stroke)

• History of traumatic brain injury, previous deep brain surgery

• Current substance or alcohol abuse

• Reduced life expectancy less than six months

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Other:
• blood samples collection
Blood samples will be drawn at baseline and at 6 and 12 months from baseline

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Istituto Nazionale di Ricovero e Cura per Anziani

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prognostic role of epigenetic biomarkers with respect to the advancing of PD motor decline	Change of Unified Parkinson's Disease Rating Scale (UPDRSIII) in relation to the baseline methylation status of the following epigenetic biomarkers: CpG loci cg17445913, cg02920897 and cg01754178. PD motor decline will be defined by an increase of UPDRS III at least of 2.4 points/year.	Baseline and 12 months later
Secondary	Prognostic role of genetic biomarkers with respect to the advancing of PD motor decline	Change of Unified Parkinson's Disease Rating Scale (UPDRSIII) in relation to the presence of mutations of the GBA coding variants rs2230288 and rs75548401. PD motor decline will be defined by an increase of UPDRS III at least of 2.4 points/year.	Baseline and 12 months later
Secondary	Prognostic role of bone sialoprotein (BSP) with respect to the advancing of PD motor decline	Change of Unified Parkinson's Disease Rating Scale (UPDRSIII) in relation to the levels of baseline bone sialoprotein (BSP). PD motor decline will be defined by an increase of UPDRS III at least of 2.4 points/year.	Baseline and 12 months later
Secondary	Prognostic role of osteomodulin (OMD) with respect to the advancing of PD motor decline	Change of Unified Parkinson's Disease Rating Scale (UPDRSIII) in relation to the levels of baseline osteomodulin (OMD).	Baseline and 12 months later
Secondary	Prognostic role of aminoacylase-1 (ACY1) with respect to the advancing of PD motor decline	Change of Unified Parkinson's Disease Rating Scale (UPDRSIII) in relation to the levels of baseline aminoacylase-1 (ACY1).PD motor decline will be defined by an increase of UPDRS III at least of 2.4 points/year.	Baseline and 12 months later
Secondary	Prognostic role of growth hormone receptor (GHR) with respect to the advancing of PD motor decline	Change of Unified Parkinson's Disease Rating Scale (UPDRSIII) in relation to the levels of baseline growth hormone receptor (GHR).PD motor decline will be defined by an increase of UPDRS III at least of 2.4 points/year.	Baseline and 12 months later