NCT05065671

Microbiome Derived Metabolism and Pharmacokinetics

Incorporating Drug Metabolism by the Human Gut Microbiome Into Personalized Medicine

• Status: Unknown
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 14 (estimated)
• Sponsor: Rutgers, The State University of New Jersey · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Accepted

Summary

The investigators will perform single-dose pharmacokinetic (PK) studies in humans following administration of drugs with known microbiome derived metabolism (MDM) in parallel with preclinical studies. By directly comparing laboratory measurements to clinical results, the investigators will be able to confirm the relevance of MDM in vivo, create microbiome-dependent PK profiles of the MDM positive drugs, and establish methodology to capture the contribution of MDM to inter-individual variability in clinical drug PK profiles.

Detailed description

The human gut microbiome has been shown to play an important role in the observed inter-individual variability in therapeutic response, including both efficacy and toxicity. One of the mechanisms by which the gut microbiome exerts these effects is through the direct biochemical transformation of orally administered drugs into more or less active or toxic metabolites, termed herein microbiome-derived drug metabolism (MDM). Recent systematic studies have revealed an enormous and largely unexplored biochemical capacity of human gut bacteria - cultured in ex vivo microbial communities or as single isolates - to metabolize dozens of orally administered drugs but the clinical relevance of the observed MDM remains unmapped. This gap in knowledge is a result of overt disconnect between preclinical and clinical studies: MDM studies performed in the laboratory are removed from direct clinical comparisons, and human studies performed during drug development and therapeutic interventions almost completely ignore microbiome contribution. Moreover, there is currently a lack standardized experimental methods and mathematical models to start incorporating MDM into clinical decisions. Our PK studies are aimed at developing such strategies into clinical practice.

Conditions

• Microbial Colonization

Interventions

Type	Name	Description
DRUG	Tolcapone 100 MG	Tolcapone 100 mg by mouth once
DRUG	Duloxetine 20 MG	Duloxetine 20 mg by mouth once

Timeline

• Start date: 2022-02-01
• Primary completion: 2025-12-01
• Completion: 2025-12-31
• First posted: 2021-10-04
• Last updated: 2024-11-14

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study