The Dutch Parkinson and Cognition Study

NCT ID: NCT04180865

Last Updated: 2019-11-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

150 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-10-01

Study Completion Date

2023-10-01

Brief Summary

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Parkinson Disease (PD) is a heterogeneous, progressive neurodegenerative disorder which is characterized by a variety of motor and non-motor symptoms. The DUPARC study is a single-centre longitudinal cohort study aimed at deeply phenotyping newly diagnosed PD patients. The main aim is to investigate the relationship between cognitive impairment and both cholinergic and dopaminergic neurodegeneration in the early stages of the disease. In addition, gastrointestinal and visual system dysfunction in PD and their role in the underlying pathology are further explored in a longitudinal setup. Treatment-naïve participants will undergo extensive motor- and non-motor assessment, imaging, and microbiome assessment at time of diagnosis, and will be followed for at least 3 years.

Detailed Description

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Rationale:

Parkinson's disease (PD) is characterized by both motor and non-motor symptoms, including cognitive decline. Mild cognitive impairment (PD-MCI) is already present at time of diagnosis in 24-36% of PD patients. Cognitive impairment in PD is associated with both cholinergic and dopaminergic deficiencies in the brain. Although dopaminergic neuronal degeneration is quite well established in relationship to the motor impairment, the rate and extent of the cholinergic neuronal degeneration in the course of PD is unknown. It is also unclear how cholinergic and dopaminergic degeneration contributes to cognitive deficits found in early and more advanced PD and its role in the progression over time.

Objectives:

The primary objective is to establish the relationship between cognitive impairment and cholinergic neurodegeneration in de novo PD patients, by studying cholinergic imaging using \[ 18 F\]Fluoroethoxy-Benzovesamicol (\[18F\]FEOBV) positron emission tomography (PET) and neuropsychological performance over time.

Secondary objectives include: (1) the investigation of possible predictive factors using optical coherence tomography and (2) to determine the relative contributions of PD diagnosis and dopaminergic medication use to the changes in microbiota composition observed in PD patients.

Study design:

At baseline patients will undergo the following investigations and questionnaires: Demographics, detailed medical history, neuropsychological assessment, imaging including MRI brain, dopaminergic Fluoro-18-L-Dihydroxyphenylalanine (18F-FDOPA) and cholinergic FEOBV PET, optical coherence tomography (OCT) and microbiota composition. At one year follow-up subjects will undergo motor-, neuropsychological, and microbiota assessment. At 3 year follow up baseline measurements will be repeated in its entirety with the exception of the genetic and gastrointestinal assessments.

Study population:

150 de novo PD patients, recruited from the neurological practices in the northern area of the Netherlands and healthy control subjects. Healthy age-,sex- and constipation-matched controls will be assessed on microbiota composition

Assessment and endpoints related to gastroenterological assessment have been approved under a separate research protocol (NL61123.042.17 - CCMO) and has been officially linked to the overall protocol.

Conditions

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Parkinson Disease

Keywords

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Parkinson Disease Treatment naive Cognition PET imaging Acetylcholine Magnetic Resonance Imaging Ophthalmology Gastrointestinal Microbiome Neurodegenerative Diseases Genetic subtyping

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Parkinson's disease patients

150 de novo treatment naive Parkinson's disease patients.

No interventions assigned to this group

Healthy control subjects

150 Healthy sex- and age-matched controls, also matched according to presence and severity of constipation, serving as a control group for microbiome composition analyses.

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

\- Diagnosis Parkinson's disease

Exclusion Criteria

* The refusal to be informed about an unforeseen clinical finding.
* Dopaminergic medication use.

Exclusion from PET imaging:

* Pregnant women
* Breast feeding women

Exclusion from MRI:

* MRI incompatible implants in the body (e.g. prosthesis, pacemakers, implanted heart valves)
* Any risk of having metal particles in the eyes due to manual work without proper eye protections
* Tattoos containing red pigments that form a safety risk.

Exclusion from gastrointestinal assessment:

* Active or persistent primary disease of the gastrointestinal tract
* History of peritonitis, severe endometriosis, abdominal, intestinal or urogenital fistula,
* Hepatobiliary or pancreatic disease (except asymptomatic cholecystolithiasis)
* History of abdominal or anorectal surgery, except minor surgery such as uncomplicated appendectomy or cholecystectomy (\>6 months ago).
* Severe gynaecological prolapse (grade III)
* Cancer and/or adjuvant treatment within the last 6 months
* Within the last three months: severe hypo- or hyperkalemia, narcosis, analgosedation, endoscopic procedure of the gastrointestinal tract, abdominal trauma
* Within the last three months: gastrointestinal tract infection, food intoxication
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Parkinson Platform Noord Nederland

UNKNOWN

Sponsor Role collaborator

University Medical Center Groningen

OTHER

Sponsor Role lead

Responsible Party

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Teus van Laar

Professor of Neurology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Teus van Laar, MD PhD

Role: STUDY_CHAIR

University Medical Center Groningen

Locations

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University Medical Center Groningen

Groningen, , Netherlands

Site Status RECRUITING

Countries

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Netherlands

Central Contacts

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Teus van Laar, MD PhD

Role: CONTACT

Phone: +31503612400

Email: [email protected]

Sygrid van der Zee, MSc

Role: CONTACT

Phone: +31503612513

Email: [email protected]

References

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Chrysou A, Heikka T, van der Zee S, Boertien JM, Jansonius NM, van Laar T. Reduced Thickness of the Retina in de novo Parkinson's Disease Shows A Distinct Pattern, Different from Glaucoma. J Parkinsons Dis. 2024;14(3):507-519. doi: 10.3233/JPD-223481.

Reference Type DERIVED
PMID: 38517802 (View on PubMed)

Boertien JM, van der Zee S, Chrysou A, Gerritsen MJJ, Jansonius NM, Spikman JM, van Laar T; PPNN Study Group. Study protocol of the DUtch PARkinson Cohort (DUPARC): a prospective, observational study of de novo Parkinson's disease patients for the identification and validation of biomarkers for Parkinson's disease subtypes, progression and pathophysiology. BMC Neurol. 2020 Jun 13;20(1):245. doi: 10.1186/s12883-020-01811-3.

Reference Type DERIVED
PMID: 32534583 (View on PubMed)

Other Identifiers

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NL60540.042.17

Identifier Type: REGISTRY

Identifier Source: secondary_id

201700171

Identifier Type: -

Identifier Source: org_study_id