Microbiome Derived Metabolism and Pharmacokinetics

NCT ID: NCT05065671

Last Updated: 2024-11-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-01
• Study Completion Date: 2025-12-31

Brief 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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Tolcapone

Tolcapone 100 mg by mouth once

Group Type: EXPERIMENTAL

Tolcapone 100 MG

Intervention Type: DRUG

Tolcapone 100 mg by mouth once

Duloxetine

Duloxetine 20 mg by mouth once

Group Type: EXPERIMENTAL

Duloxetine 20 MG

Intervention Type: DRUG

Duloxetine 20 mg by mouth once

Interventions

Tolcapone 100 MG

Tolcapone 100 mg by mouth once

Intervention Type: DRUG

Duloxetine 20 MG

Duloxetine 20 mg by mouth once

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 18 to 65 years of age
• Body mass index between 18.5 - 29.9 kg/m2

Exclusion Criteria

• Estimated creatinine clearance < 50 mL/min
• Liver impairment (liver enzymes > 2 times upper limit)
• Antibiotics in the past 3 months
• History of gastrointestinal disease
• History of autoimmune disorder
• Chronic viral infection
• Smoker
• Alcohol intake (defined as having up to 1 drink per day for women and up to 2 drinks per day for men)
• Use of immune modulating medications
• Diabetes mellitus
• Any history or contraindication to the study medications

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Rutgers, The State University of New Jersey

OTHER

Sponsor Role: lead

Responsible Party

Luigi Brunetti

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Robert Wood Johnson University Hospital Somerset

Somerville, New Jersey, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Luigi Brunetti, PhD

Role: CONTACT

luigi.brunetti@rutgers.edu

908-595-2645

Mohamed Donia, PhD

Role: CONTACT

donia@princeton.edu

609-258-5870

Facility Contacts

Luigi Brunetti, PhD

Role: primary

luigi.brunetti@rutgers.edu

9085952645

Other Identifiers

Pro2021000945

Identifier Type: -

Identifier Source: org_study_id