Aquaporin-4 Single Nucleotide Polymorphisms in Patients With Idiopathic and Familial Parkinson's Disease

Parkinson Disease Clinical Trial

Official title:

Study on the Effects of Single Nucleotide Polymorphisms in Aquaporin-4 (AQP4) Gene on the Clinical Phenotype in Patients With Idiopathic and Familial Parkinson's Disease.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04553185
• Other study ID #: 2020 21/02
• Status: Recruiting
• Start date: November 28, 2018
• Est. completion date: September 1, 2024

Study information

• Verified date: November 2023
• Source: University of Exeter
• Contact: Edoardo r De Natale, MD MSc PhD
• Phone: 07503741242
• Email: e.de-natale[@]exeter.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to understand the relationship between problems in sleep, genetic variations in the Aquaporin-4 gene (AQP4), and the development of Parkinson's Disease.

Description:

Parkinson's Disease (PD) is a progressive neurodegenerative disease characterized by the abnormal deposition in the brain of aggregates called Lewy Bodies, packed with a protein called α-synuclein. The mechanisms why this protein accumulates in the brain of patients with PD, as well as its relationship with clinical symptoms, is unknown. Recently, an internal mechanism of drainage of waste proteins called glymphatic system has been identified and characterized. This system is silent during wakefulness and works during sleep. When it is active, a virtual space between the blood capillaries and cells of the brain called astrocytes opens and lets out waste products from the brain. This process is mediated by a protein of the astrocytes called Aquaporin-4 (AQP4). Preclinical studies have shown that the function of this system could be critical for the clearance of β-amyloid, a protein linked with the development of Alzheimer's Disease. Studies in humans have shown that genetic variations some parts of the AQP4 gene, defined as single nucleotide polymorphisms, may increase the likelihood to develop an aggressive form of Alzheimer's Disease. However, no studies in humans have ever been performed in Parkinson's disease and α-synuclein. In this study, the investigators aim to elucidate whether genetic variations in the AQP4 gene contribute to variations in the clinical presentation and progression of sporadic and genetic forms of Parkinson's disease. To do so, the genetic profile of patients will be determined through a small venous blood sample collection. This will be coupled with clinical and sleep assessment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 800
• Est. completion date: September 1, 2024
• Est. primary completion date: September 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• 18-85 years of age
• Able to give informed consent
• Able to perform online neuropsychological examinations
• Diagnosis of PD according to Brain Bank Criteria
• No presence or personal or family history of other neurological or psychiatric disorders

Exclusion Criteria:

• Presence of other neurological disorders and known intracranial co-morbidities such as stroke, haemorrhage, space-occupying lesions
• Inability to perform online neuropsychological assessment
• Inability to have access to informatics technology to perform the online assessment tests
• Inability to travel for the assessments
• Native language different from English

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Other:
• Study procedure
All participants will undergo a collection of demographic data, personal and family history for PD, a neurological examination and administration of clinical scales. All participants will undergo a collection of venous blood sample. At the end of the visit they will receive a wristwatch to monitor their sleep at home (Actigraph) and a sleep diary, together with a prepaid envelope to post the watch and the diary back to the investigators. They will also receive a link for a series of online tests for non-motor symptoms related to Parkinson's disease that they can complete remotely at home.

Locations

Country	Name	City	State
United Kingdom	East Kent University Hospitals NHS Foundation Trust	Ashford
United Kingdom	University of Exeter	Exeter
United Kingdom	Prince Phillip Hospital	Llanelli
United Kingdom	Lewisham and Greenwich NHS Foundation Trust	London

Sponsors (1)

Lead Sponsor	Collaborator
University of Exeter

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Association between genetic variations in the AQP4 gene and worse motor symptoms in PD patients	The presence of genetic variations in the AQP4 gene, measured with single nucleotide polymorphisms will be correlated, in idiopathic and familial PD patients, with higher (worse) scores on the Hoehn & Yahr scales	Up to 36 months
Primary	Association between genetic variations in the AQP4 gene and worse cognitive symptoms in PD patients	The presence of genetic variations in the AQP4 gene, measured with single nucleotide polymorphisms will be correlated, in idiopathic and familial PD patients, with lower (worse) scores on Montreal Cognitive Assessment (MoCA) scale	Up to 36 months
Primary	Association between genetic variations in the AQP4 gene and worse sleep symptoms in PD patients	The presence of genetic variations in the AQP4 gene, measured with single nucleotide polymorphisms will be correlated, in idiopathic and familial PD patients, with worse sleep performances as assessed with sleep scales and Actigraph	Up to 36 months
Primary	Association between genetic variations in the AQP4 gene and worse non-motor symptoms in PD patients	The presence of genetic variations in the AQP4 gene, measured with single nucleotide polymorphisms will be correlated, in idiopathic and familial PD patients, with higher (worse) scores on scales for non-motor symptoms.	Up to 36 months
Secondary	Association between genetic variations in the AQP4 gene and altered levels of glymphatic system markers in PD patients	The presence of genetic variations in the AQP4 gene, measured with single nucleotide polymorphisms will be correlated, in idiopathic and familial PD patients, with increased levels of blood concentration of LRP-1, ABCB1 and AQP4	Up to completion of study
Secondary	Association between genetic variations in the AQP4 gene and altered levels of astrocytic	The presence of genetic variations in the AQP4 gene, measured with single nucleotide polymorphisms will be correlated, in idiopathic and familial PD patients, with increased levels of blood concentration of S100ß	Up to completion of study
Secondary	Association between genetic variations in the AQP4 gene and altered levels of protein aggregation markers in PD patients	The presence of genetic variations in the AQP4 gene, measured with single nucleotide polymorphisms will be correlated, in idiopathic and familial PD patients, with increased levels of blood concentration of a-synuclein	Up to completion of study