Finding natural blood and urine markers that predict how your liver metabolizes drugs

Endobiotics for Phenotyping Cytochrome P450 Enzymes: Using Metabolomics to Identify Novel Endogenous CYP2C19 Activity Biomarkers in Healthy Volunteers

This project tries to see if natural compounds in blood and urine can predict CYP2C19 liver enzyme activity in healthy adults.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: University Hospital, Geneva (Academic / other)
• Locations: 1 site (Geneva)
• Trial ID: NCT07014930 on ClinicalTrials.gov

What this trial studies

This single-centre, open-label Phase 1 trial will enroll 40 healthy adults at Geneva University Hospitals and divide them into 10 poor metabolizers and 30 non-poor metabolizers by CYP2C19 genotype. Each participant will complete three sessions: baseline phenotyping after a single 10 mg oral dose of omeprazole, an inhibition phase after 7 days of fluvoxamine, and an induction phase after rifampicin, with 24-hour urine collections and plasma and extracellular vesicle sampling at each session. Untargeted metabolomic profiling using UHPLC-HRMS will be performed on plasma, extracellular vesicles, and urine to search for endogenous compounds associated with CYP2C19 activity. The protocol compares genetic, inhibited, and induced enzyme states to identify candidate endogenous biomarkers that could serve as non-invasive phenotyping tools.

Who should consider this trial

Good fit: Healthy French-speaking adults aged 18–65 with BMI 18–27 who can use barrier contraception if applicable and who are genotyped as CYP2C19 poor metabolizers or normal/rapid/ultrarapid metabolizers and can attend three sessions in Geneva are ideal candidates.

Not a fit: People with intermediate CYP2C19 genotypes, pregnant or breastfeeding individuals, those with liver disease, regular heavy smokers, or anyone taking medications or foods that affect CYP activity are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this could provide a non-invasive biomarker test to predict CYP2C19 activity and help personalize drug dosing without needing probe drugs.

How similar studies have performed: Omeprazole probe-drug phenotyping is an established method and metabolomics has identified biomarkers for other enzymes, but validated endogenous biomarkers specific to CYP2C19 remain largely unproven.

Eligibility criteria

Inclusion Criteria:

* Healthy men and women
* Age 18-65 years
* Body Mass Index (BMI) 18-27
* Understanding of French language and able to give a written inform consent
* CYP2C19 genotype: PMs, NMs, RMs or UMs
* At least one barrier method contraception during the whole study and 1 month after the end of the study (in addition of hormonal contraception if applicable)

Exclusion Criteria:

* CYP2C19 IMs
* Participation in any other interventional clinical study within 3 months prior to inclusion
* Pregnant or breastfeeding woman
* Any pathologies, use of drugs or food that may affect CYP activity (based on the 'drug interactions and cytochromes P450 table published by the Service of Clinical Pharmacology and Toxicology, HUG50 and on the investigator's knowledge)
* Medical history of liver transplantation
* Regular smokers of ≥ 10 cigarettes/day
* Alcohol intake 2 days prior to session 1 and during fluvoxamine and rifampicin intake
* Alteration of hepatic tests (ASAT, ALAT, GGT, bilirubin more than 3x normal)
* Renal failure (serum urea, serum creatinine and eGFR outside the norms)
* Medical history of chronic alcoholism or abuse of psychoactive drugs
* Sensitivity to any of the drugs used
* Psychiatric disorders
* Beck Score ≥10 (question related to suicide \>0)
* Contact lens wearers

Where this trial is running

Geneva

• The Geneva University Hospitals (HUG) — Geneva, Switzerland (Recruiting)

Study contacts

• Study coordinator: Yahia Bennani, Master's degree

Conditions Healthy Volunteers