AADC/TDC in Advanced Parkinson's Disease

Parkinson Disease Clinical Trial

Official title: Aromatic L-amino Acid Decarboxylase Activity, Tyrosine Decarboxylase Activity and Gut Microbiome in Patients With Advanced Parkinson's Disease

Status Recruiting

Clinical Trial Summary

Rationale: Many persons with Parkinson's disease (PD) develop a progressive resistance to levodopa, which is the pharmacological mainstay of PD treatment. Recently, two enzymatic pathways have been identified that could be (partially) responsible for this: 1) breakdown of levodopa by bacterial tyrosine decarboxylase (TDC), an enzyme which normally decarboxylates dietary tyrosine but which is also able to decarboxylate levodopa. Accumulation of bacterial TDC in the small intestine, such as in the context of small-intestinal bacterial overgrowth (SIBO) - for which persons with PD are at increased risk - has the potential to prematurely metabolize levodopa, hence limiting its bioavailability and effect. 2) paradoxical induction of activity of the enzyme aromatic L-amino acid decarboxylase (AADC) in chronic users of levodopa combined with a peripheral decarboxylase inhibitor, also leading to a premature breakdown of levodopa and limitation of its bioavailability and effect.

Primary objective: in a cross-sectional sample of advanced (≥5 years) Parkinson's disease determining the prevalence of increased bacterial TDC activity in feces, and the prevalence of increased AADC activity in serum.

Secondary objective: correlating these biomarkers to clinical parameters, correlating composition of the microbiome to TDC activity, to the presence of levodopa resistance, and to factors related to socio-economic status.

Study design: using feces, serum samples and clinical data from n=50 participants, the relevant enzymes' activity will be measured and the composition of the gut microbiome will be determined. These will be correlated to the clinical and demographic parameters.

Clinical Trial Description

n/a

Related Conditions & MeSH terms

• Parkinson Disease

• NCT number: NCT05558787
• Study type: Observational
• Source: Radboud University Medical Center
• Contact: M. Beckers, MSc
• Phone: +31 (0) 24 361 33 92
• Email: parkinsoncentrum@radboudumc.nl
• Status: Recruiting
• Start date: June 28, 2023
• Completion date: July 2025