Clinical trial NCT04553185: Aquaporin-4 Single Nucleotide Polymorphisms in Patients with Idiopathic and Familial Parkinson's Disease
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.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Parkinson Disease
Keywords: Parkinson's disease
AQP4
Glymphatic System
Genetics
Lead sponsor: University of Exeter
Sponsor class: OTHER
First posted: 2020-09-17
Enrollment: 800
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with a diagnosis of Parkinson's disease according to Published Criteria.

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Association between genetic variations in the AQP4 gene and worse motor symptoms in PD patients
timeFrame: Up to 36 months
measure: Association between genetic variations in the AQP4 gene and worse cognitive symptoms in PD patients
timeFrame: Up to 36 months
measure: Association between genetic variations in the AQP4 gene and worse sleep symptoms in PD patients
timeFrame: Up to 36 months
measure: Association between genetic variations in the AQP4 gene and worse non-motor symptoms in PD patients
timeFrame: Up to 36 months
Secondary outcomes:
measure: Association between genetic variations in the AQP4 gene and altered levels of glymphatic system markers in PD patients
timeFrame: Up to completion of study
measure: Association between genetic variations in the AQP4 gene and altered levels of astrocytic
timeFrame: Up to completion of study
measure: Association between genetic variations in the AQP4 gene and altered levels of protein aggregation markers in PD patients
timeFrame: Up to completion of study
Other outcomes:
Locations:
city: Ashford
country: United Kingdom
facility: East Kent University Hospitals NHS Foundation Trust
city: Exeter
country: United Kingdom
facility: University of Exeter
city: Llanelli
country: United Kingdom
facility: Prince Phillip Hospital
city: London
country: United Kingdom
facility: Lewisham and Greenwich NHS Foundation Trust
Study officials:
affiliation: University of Exeter
name: Marios Politis, MD MSc PhD
role: STUDY_CHAIR
References: