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

November 30, 2023 updated by: University of Exeter

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.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Estimated)

800

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients with a diagnosis of Parkinson's disease according to Published Criteria.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Parkinson's disease patients
Patients with idiopathic or familial Parkinson's disease
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Association between genetic variations in the AQP4 gene and worse motor symptoms in PD patients
Time Frame: Up to 36 months
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
Association between genetic variations in the AQP4 gene and worse cognitive symptoms in PD patients
Time Frame: Up to 36 months
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
Association between genetic variations in the AQP4 gene and worse sleep symptoms in PD patients
Time Frame: Up to 36 months
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
Association between genetic variations in the AQP4 gene and worse non-motor symptoms in PD patients
Time Frame: Up to 36 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Association between genetic variations in the AQP4 gene and altered levels of glymphatic system markers in PD patients
Time Frame: Up to completion of study
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
Association between genetic variations in the AQP4 gene and altered levels of astrocytic
Time Frame: Up to completion of study
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 S100β
Up to completion of study
Association between genetic variations in the AQP4 gene and altered levels of protein aggregation markers in PD patients
Time Frame: Up to completion of study
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 α-synuclein
Up to completion of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Exeter

Investigators

  • Study Chair: Marios Politis, MD MSc PhD, University of Exeter

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 28, 2018

Primary Completion (Estimated)

September 1, 2024

Study Completion (Estimated)

September 1, 2024

Study Registration Dates

First Submitted

August 26, 2020

First Submitted That Met QC Criteria

September 11, 2020

First Posted (Actual)

September 17, 2020

Study Record Updates

Last Update Posted (Estimated)

December 1, 2023

Last Update Submitted That Met QC Criteria

November 30, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2020 21/02

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

There is no plan to share IPD with other researchers.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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