Observational Small Intestine and Blood Fingerprint (SmIle) Study in Parkinson's Disease

Study Overview
=================
Brief Summary
-----------------
Observational cross-sectional study in PD patients and healthy controls (HC) using an investigational medical device consisting of a passive small intestine microbiome aspiration (SIMBA) system (capsule) that is ingested orally and recovered together with the stools (home recovery) together with blood sampling (during the onsite visit).

Detailed Description
-----------------
Participants will be swallowing two SIMBA capsules which allows for minimally-invasive sampling of the microbiome and metabolome deep in the small intestine. Researchers will use the capsule samples to determine the small intestinal microbiome and metabolomic signatures in luminal fluid samples from the small bowel in Parkinson Disease (PD) patients compared to healthy controls (HC).

Official Title
-----------------
Observational, Cross-sectional Clinical Study in Parkinson's Disease (PD) Patients and Healthy Controls (HC) to Identify PD Specific Microbial and Metabolic Fingerprints in Small Intestinal (SI) Fluid and Blood

Conditions
-----------------
Parkinson Disease

Intervention / Treatment
-----------------
* Device: Fluid biopsy capsule
* Drug: Levodopa-Carbidopa Immediate Release


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Subjects are eligible to be included in the study only if all of the following criteria apply: Males and females aged 50-85 years old at time of on-site visit Signed Informed consent Willing & able to comply with study procedures (including SIMBA capsule ingestion) and have study assessments performed Able to swallow a size-00 capsule (23mm length) in OFF state Additional inclusion criteria for PD patients only Diagnosis of idiopathic PD (Clinically Probable PD), including documented levodopa responsiveness Treatment with an immediate release levodopa formulation during the day at a stable dose for at least 2 months prior to enrollment Exclusion Criteria Subjects are excluded from the study if any of the following criteria apply: Any risk of capsule non-excretion, including, e.g., prior gastrointestinal disease, surgery, or radiation treatment which, in the Investigator's opinion, would lead to intestinal structuring or obstruction, achalasia, eosinophilic esophagitis, any inflammatory bowel disease (IBD), cancer diagnosis or treatment within the past year, or previous esophageal, gastric, small intestinal, or colonic surgery; appendectomy or cholecystectomy more than 3 months prior to on-site study visit are acceptable, Use of any medications in the week prior to the on-site study visit, unless part of regular treatment, that could substantially alter gastrointestinal motor function (e.g., opioids, prokinetics, anticholinergics); laxative use is allowed provided that it is kept unchanged in the week prior to the study visit. PPIs are allowed provided a wash-out period of 48 hours is respected before swallowing the SIMBA capsules and PPI treatment is resumed only 4 hours thereafter, Any contraindication for using domperidone, including a long QT interval, concomitant use of QT prolonging drugs, any risk of significant electrolyte abnormality, known hypersensitivity, known liver impairment or significant (e.g. unstable) cardiac disease (see label) putting the subject at significant risk according to the investigator's clinical judgement History of oropharyngeal dysphagia, or other swallowing disorder with a risk of capsule aspiration, e.g. SDQ score > 4, Any concomitant PD treatment, including any dopamine agonist and MAO-B inhibitor, except (for PD patients only) an immediate release levodopa formulation during the day (required per inclusion criterion), the concomitant use of a decarboxylase inhibitor and the use of a controlled release levodopa formulation at bedtime, Major genital and/or rectum prolapse, Any concomitant or previous treatment (<2 months from on-site study visit) with significant anti-inflammatory or immune suppressant medication, e.g. DMARDs, biologicals or systemic corticosteroids, except non-chronic PRN use of an NSAID and/or 5-ASA (mesalazine) treatment, Active cancer, including any prolactinoma, within 5 years (allowed: uncomplicated basal cell carcinoma and successfully removed carcinoma in situ), Clinically significant immune deficiency (according to Investigator's judgement), Documented HIV infection, or any clinically significant systemic infection, Antibiotic use (except for local use), use of prebiotics, or probiotics ≤12 weeks prior to on-site study visit, or Fecal Microbiota Transplantation anytime in medical history Dementia in medical history or identified by a MMSE <24, Insulin-dependent diabetes mellitus, Current Psychosis episode by clinical judgement based on anamnesis Active significant impulse control disorder (by clinical judgement and based on interview and medical records) Pregnancy Alcohol or drug abuse Deep brain stimulation or Duodopa/Lecigon treatment. Subject, according to investigator assessment, not expected to be able to comply with study procedures including SIMBA capsule recovery and SIBO breath test execution with - or without help (when home).

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy control (HC)<br>25 neurotypical controls, age-matched to the Parkinson's disease group | Device: Fluid biopsy capsule<br>* Ingestion of two SIMBA capsules<br>|
| Parkinson's disease (PD)<br>75 Parkinson's disease patients | Device: Fluid biopsy capsule<br>* Ingestion of two SIMBA capsules<br>Drug: Levodopa-Carbidopa Immediate Release<br>* Single dose, Levodopa-Carbidopa Immediate Release<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in microbiome profile of small intestine samples between groups | Functional dysbiosis profile of the small intestinal microbiota of Parkinson's Disease patients compared to age-matched neurotypical controls, as determined by whole metagenome shotgun sequencing based profiling | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in blood metabolome composition between groups | Blood metabolome composition profile of Parkinson's Disease patients as compared to age-matched neurotypical controls, as determined by metabolomics analysis | Baseline | 
| Correlation between the observed small intestine microbiome profile and blood metabolome composition, including, in PD subjects, levodopa pharmacodynamics | Small intestinal and blood pharmacodynamics of Levodopa as a function of small intestinal microbiota profiles, as determined by blood and small intestinal metabolomics and small intestinal whole metagenome shotgun profiling and appropriate statistical correlation methods | Baseline |