Assessing the Polygenic Burden of Rare Disruptive Mutations in Parkinson's Disease

Parkinson Disease Clinical Trial

Official title:

Assessing the Polygenic Burden of Rare Disruptive Mutations in Parkinson's Disease: a Novel Diagnostic Test to Predict Parkinson's Disease Risk

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04620980
• Other study ID #: RF-2019-12370224
• Status: Recruiting
• Start date: June 15, 2021
• Est. completion date: May 17, 2024

Study information

• Verified date: September 2022
• Source: Neuromed IRCCS
• Contact: Teresa Esposito, PhD
• Phone: +39 0865915249
• Email: teresa.esposito[@]igb.cnr.it
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The project intends to assess the polygenic burden of rare disruptive mutations in Parkinson's disease (PD) and how they influence the phenotype/pathological heterogeneity of disease.

Description:

The investigators intend to extend the genetic analysis to a cohort of 300 PD cases and 300 healthy subjects (wife / husband of the patients) that will be recruited at Scientific Institute for Research, Hospitalization and Healthcare (IRCCS) Neuromed.

After signed informed consent patients will be assessed for disease progression (Hoehn and Yahr stadium, Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS), Montreal Cognitive Assessment (MoCA) test, no motor symptoms, therapy and levodopa induced Dyskinesia (LID) occurrence). Each patient and control will be subjected to peripheral blood sampling for the isolation of DNA, RNA, plasma and serum. The investigators will use a disease-specific gene panel including about 100 genes related to Parkinson's Disease, autophagy and levodopa induced Dyskinesia (LID).

Bioinformatics analysis will allow to catalog in a database the identified variants/mutations according to their frequency and characteristics.

The investigators will specifically assess if the inheritance of multiple rare deleterious variants in Parkinson's Disease genes is predictive of disease risk.

The presence of one or more variants will be tested for association with phenotypic manifestation of Parkinson's Disease (motor, non-motor, and cognitive signs, as well as age at onset, LID and neuroimaging changes) to assess the variant burden effect on progression, and prognosis of the disease.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: May 17, 2024
• Est. primary completion date: September 30, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Presence of at least two out the following cardinal signs: resting tremor, cogwheel rigidity, bradykinesia, asymmetrical onset of symptoms and symptomatic response to L-dopa (levodopa).

Exclusion Criteria:

• Previous thalamotomy on the implanted sides;

• Significant brain atrophy or structural damage seen on CT or MRI;

• Marked cognitive dysfunction;

• Active psychiatric symptoms;

• Concurrent neurological disorders;

• Other uncontrolled medical disorders.

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Diagnostic Test:
• targeted resequencing
The investigators will use a disease-specific gene panel including about 100 genes related to Parkinson's Disease, autophagy and levodopa induced Dyskinesia (LID).

Locations

Country	Name	City	State
Italy	IRCCS Neuromed	Pozzilli

Sponsors (1)

Lead Sponsor	Collaborator
Neuromed IRCCS

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	clinical evaluation of PD patients and controls	disease progression (Hoehn and Yahr stadium, MDS-UPDRS part III, MoCA test, no motor symptoms, therapy and LID occurrence	three years
Primary	identification of variants/mutations	assessing if the inheritance of multiple rare deleterious variants in PD genes is predictive of PD risk.	two years
Primary	association with phenotypic manifestation of PD	The presence of one or more variants will be tested for association with phenotypic manifestation of PD (motor, non-motor, and cognitive signs, as well as age at onset, LID and neuroimaging changes) to assess the variant burden effect on progression, and prognosis of the disease.	three years