Untreated Parkinson's Disease Work-up Assessing Resident Microbiota and Duodenal Barrier Function

NCT07418658 | Not Yet Recruiting

• 1 other identifier: s71449
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The UPWARD study is a prospective hypothesis-generating study in individuals with untreated Parkinson's disease (PD) and age-matched healthy controls (HCs). The objective of the study is to characterise disease-driven gastrointestinal (GI) changes that occur prior to initiation of treatment. The main questions this study aims to answer are:

1. 1.Are there changes in duodenal permeability in people with untreated PD?
2. 2.Are there changes in the gut microbiome in people with untreated PD?
3. 3.Are these gut changes linked to prodromal features, or movement and non-movement symptoms of PD?

Conditions

Parkinson's Disease (PD)

Keywords

Gut Microbiome; Intestinal Permeability; Drug-Naïve

Outcome Measures

Primary Outcomes (4)

• Paracellular flux

  After mounting duodenal mucosal biopsies on Ussing chambers, the paracellular permeability is measured by adding a fluorescently labelled dextran to the luminal side and quantifying cumulative paracellular flux to the basolateral side at serial time points.

  On day 7 (Follow-up visit)

• Transepithelial electrical resistance (TEER)

  After mounting duodenal mucosal biopsies on Ussing chambers, the TEER will be measured by applying an electrical current and recording the resulting change in potential difference (PD).

  On day 7 (Follow-up visit)

• Fecal microbiota composition

  The fecal microbiota composition will be analysed on fecal samples using techniques including (but not limited to) 16s rRNA sequencing.

  Analyses wil be performed after storage of stool samples, collected during the at-home phase (day 1-6) preceding the Follow-up visit on day 7.

• Duodenal microbiota composition

  The duodenal microbiota composition will be analysed on duodenal samples obtained by gastroduodenoscopy using techniques including (but not limited to) 16s rRNA sequencing.

  Analyses wil be performed after storage of duodenal samples, collected during the gastroduodenoscopy on day 7 (Follow-up visit).

Study Arms (2)

Drug-Naïve Parkinson's disease patients

Other: Invasive sampling procedures; Other: Non-invasive sampling procedures

Age-matched healthy controls

Other: Invasive sampling procedures; Other: Non-invasive sampling procedures

Interventions

Invasive sampling procedures OTHER

Invasive sampling procedures in the study include an (optional) gastroduodenoscopy with duodenal biopsies, and venous blood sampling.

Age-matched healthy controls; Drug-Naïve Parkinson's disease patients

Non-invasive sampling procedures OTHER

Non-invasive sampling procedures in this study include a clinical examination, radiopaque pellet test with an abdominal X-ray (to assess whole-gut transit time), stool sample collection, and questionnaires.

Age-matched healthy controls; Drug-Naïve Parkinson's disease patients

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patient participants will be recruited during patient consultations in the Movement Disorders Clinic of UZ Leuven. Neurologists in other hospitals may also be informed about the study, so that they may refer interested patients to UZ Leuven for potential participation in the study.

You may qualify if:

• Diagnosis of Parkinson's Disease by a neurologist according to the Movement Disorder Society Clinical Diagnostic Criteria for PD
• Signed informed consent form
• Aged 18-75 years old
• Able to understand the study and questionnaires, and comply with study requirements
• Aged 40-75 years old
• Signed informed consent form
• Able to understand the study and questionnaires, and comply with study requirements

You may not qualify if:

• Participants eligible for this study must not meet any of the following criteria:
• Patients and controls:
• Gastrointestinal: diagnosis of organic gastrointestinal diseases potentially affecting the assessments during the study (e.g. inflammatory bowel disease (IBD), celiac disease, eosinophilic diseases of the gastro-intestinal tract, gastro-intestinal cancer, diverticulitis in the last 6 months, GI infection in the last 3 months, …).
• Surgery: major abdominal surgery (including, but not limited to: cholecystectomy, colectomy, hiatal hernia repair, …) except for uncomplicated appendectomy, splenectomy and inguinal hernia repair.
• Medication use:
• Any previous exposure to medication used in the treatment of motor symptoms of Parkinson's disease (levodopa, dopamine agonists, MAO-B inhibitors, COMT-inhibitors, NMDA-receptor antagonists, anticholinergics)
• Antibiotics use in the last 3 months.
• Use of PPI in the last month.
• Use of NSAID in the last month.
• Use of anticoagulation4 (including vitamin K antagonists (VKA), direct oral anticoagulants (DOAC) or low-molecular weight heparins (LMWH)) or dual antiplatelet therapy4 (DUAPT; Acetylsalicilic acid (Asaflow®) + P2Y12-inhibitor (Clopidogrel®)).
• Pregnancy and breastfeeding.
• Other: Cancer and/or adjuvant treatment within the last 6 months
• Exposures:
• Food intoxication in the last 3 months.
• Consumptom of more than 2 standard units of alcohol per day.

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead

Study Sites (1)

UZ Leuven

Leuven, Vlaams-Brabant, 3000, Belgium

Location

Biospecimen

Retention: SAMPLES WITH DNA

1. Duodenal mucosal biopsy samples. 2. A fecal sample

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2026
• First Posted: February 18, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 1, 2029
• Last Updated: February 18, 2026

Record last verified: 2026-01

Locations

BE (1)