Parkinson DiseaseDUPARCNCT04180865
The Dutch Parkinson and Cognition Study
An observational study of Parkinson Disease, run by University Medical Center Groningen at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Parkinson Disease
- How many people
- 150 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Oct 2017to 1 Oct 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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
Who may be able to join
- Diagnosis Parkinson's disease
Who cannot join
- The refusal to be informed about an unforeseen clinical finding.
- Dopaminergic medication use.
- Pregnant women
- Breast feeding women
- 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
Show all 15Show fewer
- Tattoos containing red pigments that form a safety risk.
- 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
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
University Medical Center Groningen
Groningen, 9700RB
Teus van Laar, MD PhD
Sygrid van der Zee, MSc
About this study
Official title: The Dutch Parkinson and Cognition Study (DUPARC): A Prospective Study on Cognitive Pathology in de Novo Parkinson'Disease
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.
Read the 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.
- Conditions
- Parkinson Disease
- Keywords
- Parkinson Disease, Treatment naive, Cognition, PET imaging, Acetylcholine, Magnetic Resonance Imaging, Ophthalmology, Gastrointestinal Microbiome, Neurodegenerative Diseases, Genetic subtyping
- Medical subject headings
- Parkinson Disease, Neurodegenerative Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Parkinson's disease patients | 150 de novo treatment naive Parkinson's disease patients. | |
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
[18F]FEOBV PET
Cortical and subcortical cholinergic innervation as measured by [18F] FEOBV PET imaging
Measured: Baseline
Secondary outcomes (22)
Cognitive screening
General cognitive performance will be assessed using a cognitive screening; the Montreal Cognitive Assessment (MOCA). The MOCA test covers the important cognitive domains including memory, attention, executive function, language and visuospatial abilities, resulting in one total score of cognitive performance. MOCA score ranges between 0 and 30, with higher scores representing better performance.
Measured: baseline
Memory performance
Memory performance will be calculated as an average Z-score of two cognitive tests; the Rey auditory verbal learning test for measuring verbal memory and the location learning test for measuring visual memory. Based on established normative data, a z-score for each test outcome will be calculated, representing performance compared to an age-, gender- and educational level-matched control group. A Z-score of 0 (zero) represents a performance similar to the normative data. A positive z-score represents better performance, while a negative z-score represents worse performance. There is no minimum or maximum z-score. These z-scores from both tests will be averages to form one outcome measurement representing memory performance.
Measured: baseline
Attention and working memory performance
Attention performance will be calculated as an average Z-score of three cognitive tests; the Stroop color-word test, the digit span and the Vienna test system reaction time measurement. Based on established normative data, a z-score for each test outcome will be calculated, representing performance compared to an age-, gender- and educational level-matched control group. A Z-score of 0 (zero) represents a performance similar to the normative data. A positive z-score represents better performance, while a negative z-score represents worse performance. There is no minimum or maximum z-score. These z-scores from all three tests will be averages to form one outcome measurement representing attention performance.
Measured: baseline
Executive function performance
Executive function performance will be calculated as an average Z-score of four cognitive tests; the trail making test, the Wisconsin card sorting test, the Hayling Sentence completion test and the letter fluency test. Based on established normative data, a z-score for each test outcome will be calculated, representing performance compared to an age-, gender- and educational level-matched control group. A Z-score of 0 (zero) represents a performance similar to the normative data. A positive z-score represents better performance, while a negative z-score represents worse performance. There is no minimum or maximum z-score. These z-scores from all tests will be averages to form one outcome measurement representing executive performance.
Measured: baseline
Visouspatial abilities
Cognitive visuospatial abilities will be calculated as an average Z-score of two cognitive tests; the Judgement of line orientation and the Map search subtest of the test of everyday attention. Based on established normative data, a z-score for each test outcome will be calculated, representing performance compared to an age-, gender- and educational level-matched control group. A Z-score of 0 (zero) represents a performance similar to the normative data. A positive z-score represents better performance, while a negative z-score represents worse performance. There is no minimum or maximum z-score. These z-scores from all tests will be averages to form one outcome measurement representing visuospatial abilities.
Measured: baseline
Language performance
Language performance will be calculated as an average Z-score of two cognitive tests; the Boston Naming test and the verbal fluency test. Based on established normative data, a z-score for each test outcome will be calculated, representing performance compared to an age-, gender- and educational level-matched control group. A Z-score of 0 (zero) represents a performance similar to the normative data. A positive z-score represents better performance, while a negative z-score represents worse performance. There is no minimum or maximum z-score. These z-scores from all tests will be averages to form one outcome measurement representing language performance.
Measured: baseline
Social cognition
Social cognition abilities will be represented as a z-score calculated from the performance on the FEEST; Facial Expression of Emotion Stimuli and tests. Based on established normative data, a z-score of the test outcome will be calculated, representing performance compared to an age-, gender- and educational level-matched control group. A Z-score of 0 (zero) represents a performance similar to the normative data. A positive z-score represents better performance, while a negative z-score represents worse performance. There is no minimum or maximum z-score. These z-scores from the FEEST test represents social cognition performance.
Measured: baseline
Brain grey matter volume
Grey matter volume as measured by structural MRI.
Measured: Baseline, 3 year follow-up
resting state functional MRI
resting state functional MRI
Measured: Baseline, 3 year follow-up
MRI: Arterial spin labeling
cerebral blood perfusion as measured by arterial spin labeling MRI
Measured: Baseline, 3 year follow-up
MRI: Diffusion weighted image
White matter assessment as measured by diffusion weighted image
Measured: Baseline, 3 year follow-up
MRI: susceptibility weighted image
Brain hemorrhage and iron storage as measured by susceptibility weighted image
Measured: Baseline, 3 year follow-up
Optical Coherence tomography
Imaging of the retinal cell layers
Measured: Baseline and 3 year follow-up
fecal zonulin
fecal zonulin as one of the measures of intestinal wall permeability
Measured: baseline
Microbiota composition
Taxonomic classification of gut microbiota composition based on 16s ribosomal RNA-gene sequencing.
Measured: Baseline and 1 year follow-up
fecal alpha1-antitrypsin
fecal alpha1-antitrypsin as one of the measures of intestinal wall permeability
Measured: baseline
serum zonulin
serum zonulin as one of the measures of intestinal wall permeability
Measured: baseline
serum lipopolysaccharide binding protein
serum lipopolysaccharide binding protein as one of the measures of intestinal wall permeability
Measured: baseline
multi-sugar urinary excretion test
multi-sugar urinary excretion test as one of the measures of intestinal wall permeability
Measured: baseline
Genetic subtyping
Saliva samples will be collected for clinical-genetic subtyping based on genome wide single-nucleotide polymorphism (SNP) analysis using the Illumina Screening Array (GSA-MD)
Measured: Baseline
Movement Disorders Society Unified Parkinson's Disease Rating Scale III
Motor assessment measured by the Movement Disorders Society Unified Parkinson's Disease Rating Scale III, a scale describing motor performance specific for patients with Parkinson's disease. Score between 0 and 72, with a higher score indicating more severe motor impairment.
Measured: Baseline, 1 year follow-up, 3 year follow-up
Change in [18F] FEOBV PET over 3 years
Change in cortical and subcortical cholinergic innervation over a time period of 3 years, as measured by baseline and follow-up [18F] FEOBV
Measured: baseline, 3 year follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2019
- Study start1 Oct 2017
- Primary completion1 Oct 2023 (estimated)
- Study completion1 Oct 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Collaborators
- Parkinson Platform Noord Nederland
- Responsible party
- Principal investigator, Teus van Laar, University Medical Center Groningen
- Investigators
- Teus van Laar, MD PhD, Study chair, University Medical Center Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04180865
- Sponsor's protocol ID
- 201700171
- Other IDs
- NL60540.042.17
- Acronym
- DUPARC
- Status last verified
- Nov 2019
- First submitted
- 4 Nov 2019
- Last updated
- 29 Nov 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 38517802Boertien 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.
PubMed 32534583
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Dutch Parkinson and Cognition Study (DUPARC): A Prospective Study on Cognitive Pathology in de Novo Parkinson'Disease
- ClinicalTrials.gov ID
- NCT04180865
- Acronym / sponsor ID
- DUPARC / 201700171
- Conditions
- Parkinson Disease
- Keywords
- Parkinson Disease, Treatment naive, Cognition, PET imaging, Acetylcholine, Magnetic Resonance Imaging, Ophthalmology, Gastrointestinal Microbiome
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Collaborators
- Parkinson Platform Noord Nederland
- Study start
- 1 Oct 2017 (actual)
- Primary completion
- 1 Oct 2023 (estimated)
- Study completion
- 1 Oct 2023 (estimated)
- First posted
- 29 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Parkinson's disease patients | – | –150 de novo treatment naive Parkinson's disease patients. |
| 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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
Key inclusion criteria (1 listed)
- Diagnosis Parkinson's disease
Key exclusion criteria (15 listed)
- The refusal to be informed about an unforeseen clinical finding.
- Dopaminergic medication use.
- Pregnant women
- Breast feeding women
- MRI incompatible implants in the body (e.g. prosthesis, pacemakers, implanted heart valves)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
[18F]FEOBV PET
Time frame: Baseline
Cortical and subcortical cholinergic innervation as measured by [18F] FEOBV PET imaging
22 secondary outcomes
Cognitive screening
Time frame: baseline
Memory performance
Time frame: baseline
Attention and working memory performance
Time frame: baseline
Executive function performance
Time frame: baseline
Visouspatial abilities
Time frame: baseline
Language performance
Time frame: baseline
Social cognition
Time frame: baseline
Brain grey matter volume
Time frame: Baseline, 3 year follow-up
resting state functional MRI
Time frame: Baseline, 3 year follow-up
MRI: Arterial spin labeling
Time frame: Baseline, 3 year follow-up
MRI: Diffusion weighted image
Time frame: Baseline, 3 year follow-up
MRI: susceptibility weighted image
Time frame: Baseline, 3 year follow-up
Optical Coherence tomography
Time frame: Baseline and 3 year follow-up
fecal zonulin
Time frame: baseline
Microbiota composition
Time frame: Baseline and 1 year follow-up
fecal alpha1-antitrypsin
Time frame: baseline
serum zonulin
Time frame: baseline
serum lipopolysaccharide binding protein
Time frame: baseline
multi-sugar urinary excretion test
Time frame: baseline
Genetic subtyping
Time frame: Baseline
Movement Disorders Society Unified Parkinson's Disease Rating Scale III
Time frame: Baseline, 1 year follow-up, 3 year follow-up
Change in [18F] FEOBV PET over 3 years
Time frame: baseline, 3 year follow up
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2019.
- Derived from this study: PubMed 38517802Chrysou 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.
- Derived from this study: PubMed 32534583Boertien 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Teus van Laar, MD PhD study chair
University Medical Center Groningen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Parkinson Disease, run by University Medical Center Groningen at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 29 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Teus van Laar, MD PhD (+31503612400, t.van.laar@umcg.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
[18F]FEOBV PET (time frame: Baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04180865, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2019; AzTrials last refreshed its copy on 31 Oct 2026.