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

Not yet recruiting

• Conditions: Parkinson Disease

• Registration Number: NCT06762028
• Lead Sponsor: University of Calgary

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-12
• Study First Submitted: 2024-12-20
• Study First Submitted QC: 2025-01-03
• Last Update Submitted: 2025-01-03
• Study First Posted: 2025-01-07
• Last Update Posted: 2025-01-07
• Study Start: 2025-02-01
• Primary Completion: 2027-02-01
• Study Completion: 2027-07-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 100

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Change of Part 3 score of the MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) on L-dopa challenge test	Same day of study visit	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).

Secondary Outcome Measures

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