The Dutch Parkinson and Cognition Study

Parkinson Disease Clinical Trial

— DUPARC  

Official title:

The Dutch Parkinson and Cognition Study (DUPARC): A Prospective Study on Cognitive Pathology in de Novo Parkinson'Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04180865
• Other study ID #: 201700171
• Secondary ID: NL60540.042.17
• Status: Recruiting
• Start date: October 1, 2017
• Est. completion date: October 1, 2023

Study information

• Verified date: November 2019
• Source: University Medical Center Groningen
• Contact: Teus van Laar, MD PhD
• Phone: +31503612400
• Email: t.van.laar[@]umcg.nl
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: October 1, 2023
• Est. primary completion date: October 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Parkinson Disease

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen	Groningen

Sponsors (2)

Lead Sponsor	Collaborator
University Medical Center Groningen	Parkinson Platform Noord Nederland

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Hospital Anxiety and Depression Scale	Questionnaire assessing anxiety and depression. Scores range from 0 to 42, with higher scores indicating more severe anxiety and depression symptoms	Baseline, 1 year follow-up, 3 year follow-up
Other	Utrechtse Coping Lijst	Dutch version of the Coping List; assessing coping style. The questionnaire consists of 47 items which can all be scored on a 1-4 scale and can be filled out by the participant. A higher score indicates a stronger involvement of that coping strategy.	Baseline, 1 year follow-up, 3 year follow-up
Other	The Dysexecutive Questionnaire	Questionnaire assessing dysexecutive problems in daily life. The DEX comprises of 20 items. All items are rates in terms of frequency on a 5-point scale: 0 (never), 1 (occasionally), 2 (sometimes), 3 (fairly often), 4 (very often). Scores are summed and the total scores range from 0 to 80, with higher scores indicating greater problems with executive functioning.	Baseline, 1 year follow-up, 3 year follow-up
Other	The Dutch Multifactor Fatigue Scale	Questionnaire assessing fatigue. The questionnaire consists of 38 items which can be rated on a 5-point scale. Scores are summed, with higher scores indicating more severe fatigue reported by the participant.	Baseline, 1 year follow-up, 3 year follow-up
Other	Questionnaire for Impulsive-Compulsive Disorder in Parkinson's Disease Rating Scale	Questionnaire for Impulsive-Compulsive Disorder in Parkinson's Disease Rating Scale (QUIP) is a questionnaire with 27 yes/no questions on impulsive-compulsive behavior. The total number of questions answered with "yes" is the main outcome measurement, with a higher score indicating more impulsive-compulsive symptoms.	Baseline, 1 year follow-up, 3 year follow-up
Other	Apathy Evaluation Scale	The Apathy Evaluation Scale (AES) is a questionnaire assessing apathy, comprised of 18 items, describing the subject's thoughts, feelings, and activity in the past 4 weeks. All items are rates in terms on a 4-point scale. Scores are summed and the total score ranges from 0 to 72, with higher scores indicating more severe presence of apathy symptoms	Baseline, 1 year follow-up, 3 year follow-up
Other	Movement disorders society - Non Motor Symptom Questionnaire;	Questionnaire assessing non-motor symptoms specific for patients with Parkinson's disease. The questionnaire consists of 30 yes/no questions on the occurrence of certain non-motor symptoms. The total number of questions answered with "yes" is used as outcome measure, indicating more presence of non-motor symptoms.	Baseline, 1 year follow-up, 3 year follow-up
Other	Rapid eye movement Sleep behavioral disorders (RBD) questionnaire	Questionnaire assessing Rapid eye movement (REM) sleep behavioral disorder. The questionnaire is a 10-item questionnaire with yes/no answers, of which question 6 consists of subitems. The number of questions answered with "yes" is considered the outcome measure, with a score ranging between 0 and 13. Higher scores indicate more REM sleep behavioral disorder symptoms.	Baseline, 1 year follow-up, 3 year follow-up
Other	Dietary assessment	Dietary assessment. Participants are asked to complete a daily diary on their intake, including detailed description of what type of food/drinks, time of day and amount of intake for three consecutive days.	Baseline, 1 year follow-up
Other	Stool frequency questionnaire	Participants are asked to record their stool frequency for one week. Based on the questionnaire an average daily stoolfrequency is calculated and used as outcome measure.	Baseline, 1 year follow-up
Other	Stool consistency questionnaire	Stool consistency is recorded for one week by the patients using the Bristol Stool chart. The Bristol Stool chart is a 7 point rating scale with 1 representing separate hard lumps as stool consistency and 7 entirely liquid stool. An average is calculated representing average stool consistency for the participant.	Baseline, 1 year follow-up
Primary	[18F]FEOBV PET	Cortical and subcortical cholinergic innervation as measured by [18F] FEOBV PET imaging	Baseline
Secondary	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.	baseline
Secondary	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.	baseline
Secondary	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.	baseline
Secondary	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.	baseline
Secondary	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.	baseline
Secondary	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.	baseline
Secondary	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.	baseline
Secondary	Brain grey matter volume	Grey matter volume as measured by structural MRI.	Baseline, 3 year follow-up
Secondary	resting state functional MRI	resting state functional MRI	Baseline, 3 year follow-up
Secondary	MRI: Arterial spin labeling	cerebral blood perfusion as measured by arterial spin labeling MRI	Baseline, 3 year follow-up
Secondary	MRI: Diffusion weighted image	White matter assessment as measured by diffusion weighted image	Baseline, 3 year follow-up
Secondary	MRI: susceptibility weighted image	Brain hemorrhage and iron storage as measured by susceptibility weighted image	Baseline, 3 year follow-up
Secondary	Optical Coherence tomography	Imaging of the retinal cell layers	Baseline and 3 year follow-up
Secondary	fecal zonulin	fecal zonulin as one of the measures of intestinal wall permeability	baseline
Secondary	Microbiota composition	Taxonomic classification of gut microbiota composition based on 16s ribosomal RNA-gene sequencing.	Baseline and 1 year follow-up
Secondary	fecal alpha1-antitrypsin	fecal alpha1-antitrypsin as one of the measures of intestinal wall permeability	baseline
Secondary	serum zonulin	serum zonulin as one of the measures of intestinal wall permeability	baseline
Secondary	serum lipopolysaccharide binding protein	serum lipopolysaccharide binding protein as one of the measures of intestinal wall permeability	baseline
Secondary	multi-sugar urinary excretion test	multi-sugar urinary excretion test as one of the measures of intestinal wall permeability	baseline
Secondary	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)	Baseline
Secondary	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.	Baseline, 1 year follow-up, 3 year follow-up
Secondary	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	baseline, 3 year follow up