Management of Parkinson's disease if levodopa is broken down prematurely

Trial details

Who runs it

Stichting Radboud University Medical Center

Trial code

EU 2024-510629-24-00

Record updated

2026. február 4.

Original description

Can symptom management of persons with Parkinson's disease who have increased activity of the levodopa-metabolizing enzyme aromatic L-amino acid decarboxylase (AADC), or who have increased abundance of bacteria that produce the levodopa-metabolizing enzymes tyrosine decarboxylase (TDC), aromatic amino acid aminotransferase (AAT) or aromatic amino acid lactate dehydrogenase (ALDH), be improved by either circumventing the enzymatic mechanisms (using the dopamine receptor agonist apomorphine), or an antibiotic intervention against enzyme-producing bacteria (rifaximin), or both?Read full original descriptionShow less

Management of peripheral levodopa resistance in Parkinson’s disease

Can symptom management of persons with Parkinson's disease who have increased activity of the levodopa-metabolizing enzyme aromatic L-amino acid decarboxylase (AADC), or who have increased abundance of bacteria that produce the levodopa-metabolizing enzymes tyrosine decarboxylase (TDC), aromatic amino acid aminotransferase (AAT) or aromatic amino acid lactate dehydrogenase (ALDH), be improved by either circumventing the enzymatic mechanisms (using the dopamine receptor agonist apomorphine), or an antibiotic intervention against enzyme-producing bacteria (rifaximin), or both?

Inclusion: Subject is an adult, at least 25 years of age, of either sex; Subject lives in the Netherlands; Subject can read and understand Dutch; Subject has completed the ethics board-approved Informed Consent; Subject is willing, competent, and able to comply with all aspects of the protocol, including multiple occasions of not taking their PD medication during a 12-hour period, and biospecimen collection; Diagnosis of Parkinson’s disease (idiopathic parkinsonism) by a neurologist, according to accepted clinical criteria; Documented peripheral levodopa resistance; Serum AADC enzyme activity of >144 mU/L (in sample taken in medicated condition) AND/OR faecal abundance of levodopa-metabolizing bacteria of >90,000 fragments per million.

Exclusion: Current presence of hallucinations or delusions, or history of developing hallucinations or delusions under dopaminergic therapy. Exception: hallucinations or delusions not currently present AND currently adequately treated with a cholinesterase inhibitor to prevent recurrence; Any antibiotic therapy during the study period and in the 12 months preceding it, unless participant only participates in apomorphine substudy and is selected for inclusion based solely upon AADC activity, not bacterial abundance; Present, or in the past 14 days, use of non-selective monoamine oxidase (MAO) inhibitors (including tranylcypromine) or dual use of a selective MAO-B inhibitor (including rasagiline, safinamide) and a selective MAO-A inhibitor (including moclobemide); Significant doubt over the correctness of the diagnosis idiopathic Parkinson’s disease; Presence of dementia; Presence of gastrointestinal disease associated with impaired drug absorption (e.g. coeliac disease); Allergies to any of the investigational and non-investigational medications or constituents thereof; Present use of, or planned initiation during the study period of, advanced therapies (AT) for Parkinson’s disease including deep brain stimulation (DBS), continuous jejunal levodopa infusion (CJLI), continuous subcutaneous (fos)levodopa infusion (CSLI), apomorphine pen injections or continuous subcutaneous apomorphine infusion (CSAI); Atypical or genetic parkinsonism, or parkinsonism caused by a structural laesion of the brain; Levodopa-resistant tremor, unless the subtotal of the ‘OFF’ MDS-UPDRS III tremor scores (item 3.15-3.18) makes up less than 15% of the ‘OFF’ MDS-UPDRS III total sum score; Fear of needles/injection; Co-morbidities that would hamper interpretation of parkinsonian disability, such as coincident musculoskeletal abnormalities; Not able to stand or walk without the assistance of another person (walking aids are not an exclusion criterion); Pregnancy or breastfeeding; Documented severe and debilitating dyskinesias on levodopa, to such an extent that levodopa treatment was terminated; Contraindications to levodopa/benserazide; Present, or in the past 4 weeks, use of any probiotic preparations, unless participant only participates in apomorphine substudy and is selected for inclusion based solely upon AADC activity, not bacterial abundance.

EU CTIS 2024-510629-24-00