Clinical trial NCT04180865: The Dutch Parkinson and Cognition Study
Official title: The Dutch Parkinson and Cognition Study (DUPARC): A Prospective Study on Cognitive Pathology in de Novo Parkinson'Disease
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Parkinson Disease
Keywords: Parkinson Disease
Treatment naive
Cognition
PET imaging
Acetylcholine
Magnetic Resonance Imaging
Ophthalmology
Gastrointestinal Microbiome
Neurodegenerative Diseases
Genetic subtyping
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
Collaborators: name: Parkinson Platform Noord Nederland
First posted: 2019-11-29
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 150 PD patients who are treatment naïve at baseline, diagnosed by a movement disorders specialist, based on the Movement Disorder Society Clinical Diagnostic Criteria for PD. Patients are recruited at partnering hospitals in the northern part of the Netherlands

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: [18F]FEOBV PET
timeFrame: Baseline
Secondary outcomes:
measure: Cognitive screening
timeFrame: baseline
measure: Memory performance
timeFrame: baseline
measure: Attention and working memory performance
timeFrame: baseline
measure: Executive function performance
timeFrame: baseline
measure: Visouspatial abilities
timeFrame: baseline
measure: Language performance
timeFrame: baseline
measure: Social cognition
timeFrame: baseline
measure: Brain grey matter volume
timeFrame: Baseline, 3 year follow-up
measure: resting state functional MRI
timeFrame: Baseline, 3 year follow-up
measure: MRI: Arterial spin labeling
timeFrame: Baseline, 3 year follow-up
measure: MRI: Diffusion weighted image
timeFrame: Baseline, 3 year follow-up
measure: MRI: susceptibility weighted image
timeFrame: Baseline, 3 year follow-up
measure: Optical Coherence tomography
timeFrame: Baseline and 3 year follow-up
measure: fecal zonulin
timeFrame: baseline
measure: Microbiota composition
timeFrame: Baseline and 1 year follow-up
measure: fecal alpha1-antitrypsin
timeFrame: baseline
measure: serum zonulin
timeFrame: baseline
measure: serum lipopolysaccharide binding protein
timeFrame: baseline
measure: multi-sugar urinary excretion test
timeFrame: baseline
measure: Genetic subtyping
timeFrame: Baseline
measure: Movement Disorders Society Unified Parkinson's Disease Rating Scale III
timeFrame: Baseline, 1 year follow-up, 3 year follow-up
measure: Change in [18F] FEOBV PET over 3 years
timeFrame: baseline, 3 year follow up
Other outcomes:
measure: Hospital Anxiety and Depression Scale
timeFrame: Baseline, 1 year follow-up, 3 year follow-up
measure: Utrechtse Coping Lijst
timeFrame: Baseline, 1 year follow-up, 3 year follow-up
measure: The Dysexecutive Questionnaire
timeFrame: Baseline, 1 year follow-up, 3 year follow-up
measure: The Dutch Multifactor Fatigue Scale
timeFrame: Baseline, 1 year follow-up, 3 year follow-up
measure: Questionnaire for Impulsive-Compulsive Disorder in Parkinson's Disease Rating Scale
timeFrame: Baseline, 1 year follow-up, 3 year follow-up
measure: Apathy Evaluation Scale
timeFrame: Baseline, 1 year follow-up, 3 year follow-up
measure: Movement disorders society - Non Motor Symptom Questionnaire;
timeFrame: Baseline, 1 year follow-up, 3 year follow-up
measure: Rapid eye movement Sleep behavioral disorders (RBD) questionnaire
timeFrame: Baseline, 1 year follow-up, 3 year follow-up
measure: Dietary assessment
timeFrame: Baseline, 1 year follow-up
measure: Stool frequency questionnaire
timeFrame: Baseline, 1 year follow-up
measure: Stool consistency questionnaire
timeFrame: Baseline, 1 year follow-up
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
affiliation: University Medical Center Groningen
name: Teus van Laar, MD PhD
role: STUDY_CHAIR
References:
citation: 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.