Exploring the Relationship Between L-dopa Responsiveness and Small Intestinal Microbiome in Parkinson's Disease (LENSER)

The investigators hypothesize that small intestinal (SI) microbiome biomarkers predict the responsiveness to oral levodopa/carbidopa in people with Parkinson's disease (PwPD). The investigators will analyze the bacterial species and function of bacterial pathways influencing the responsiveness of PwPD to oral L-dopa. The investigators will pursue this goal using a reliable capsule system (SIMBA capsule, Nimble Science, Calgary, AB) that suitably captures SI luminal fluid for multi-omics analysis.

Study Overview

• Status: Not yet recruiting
• Conditions: Parkinson Disease
• Intervention / Treatment: Device: SIMBA capsule

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Davide Martino; Phone Number: 4032108726; Email: davide.martino@ucalgary.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Any patient with Parkinson disease fulfilling section criteria.

Description

Inclusion Criteria:

1. Males and females aged 50-85 years old at time of on-site visit. (ages 81-85 will be assessed on a per case basis by the principal investigator)
2. Signed Informed consent.
3. Willing & able to comply with study procedures (including SIMBA capsule ingestion) and have study assessments performed.
4. Able to swallow a size-00 capsule (25mm length) in OFF state.
5. Diagnosis of idiopathic PD (Clinically Probable PD), including documented levodopa responsiveness.
6. Treatment with an immediate release levodopa formulation during the day at a stable dose for at least 2 months prior to enrollment.

Exclusion Criteria:

1. Any risk of capsule non-excretion related to intercurrent gastrointestinal conditions.
2. 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.
3. History of oropharyngeal dysphagia, or other swallowing disorder with a risk of capsule aspiration, e.g., SDQ score > 4.
4. 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.
5. Active cancer within 5 years.
6. Clinically significant immune deficiency (according to Investigator's judgement).
7. Antibiotic use (except for local use), ≤12 weeks prior to on-site study visit, or Fecal Microbiota Transplantation anytime in medical history.
8. Use of prebiotics, or probiotics ≤2 weeks prior to the on-site study visit.
9. Dementia in medical history.
10. Insulin-dependent diabetes mellitus.
11. Current Psychosis episode by clinical judgement based on anamnesis.
12. Pregnancy.
13. Alcohol or drug abuse.
14. Deep brain stimulation or Duodopa/Lecigon treatment.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Part 3 score of the MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) on L-dopa challenge test	The primary outcome is the acute responsiveness to an immediate release L-dopa/carbidopa or L-dopa/benserazide dose, quantified as the percent change from pre-intake ("OFF" state) to full "ON" state of the Part 3 score of the MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS).	Same day of study visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
time latency to full "ON" state	Temporal period between L-dopa ingestion and full "ON" state during a single L-dopa challenge test	Same day of study visit
Part 4 score of the MDS-UPDRS	Motor fluctuations and L-dopa-induced dyskinesia	Same day of study visit
Maximum observed plasma concentration of L-dopa (Cmax)	The investigators will determine maximum observed plasma concentration (Cmax) directly from serial samples.	Same day of study visit
Time to maximum observed plasma concentration (Tmax)	The investigators will determine time to maximum observed plasma concentration (Tmax) directly from serial samples.	Same day of study visit
Area under the L-dopa concentration-time curve (0-3 hours; AUC0-3 h)	The investigators will determine the area under the L-dopa plasma concentration-time curve (0-3 hours; AUC0-3 h).	Same day as study visit

Collaborators and Investigators

• Sponsor: University of Calgary

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: December 20, 2024
• First Submitted That Met QC Criteria: January 3, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 3, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: L-dopa; small intestine; SIMBA
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease
• Other Study ID Numbers: UCalgaryREB24-1779; POP24-11461 (Other Grant/Funding Number: Weston Family Foundation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No