Microbiome Derived Metabolism and Pharmacokinetics

Microbial Colonization Clinical Trial

— MDM-PK  

Official title:

Incorporating Drug Metabolism by the Human Gut Microbiome Into Personalized Medicine

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05065671
• Other study ID #: Pro2021000945
• Status: Recruiting
• Phase: Phase 1
• Start date: February 1, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: March 2024
• Source: Rutgers, The State University of New Jersey
• Contact: Luigi Brunetti, PhD
• Phone: 908-595-2645
• Email: luigi.brunetti[@]rutgers.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 14
• Est. completion date: December 31, 2024
• Est. primary completion date: June 1, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

• Additional exclusion criteria will be based on the FDA approved prescribing information for selected drugs (i.e., contraindications)

Related Conditions & MeSH terms

• Communicable Diseases
• Infections
• Microbial Colonization

Intervention

Drug:
• Tolcapone 100 MG
Tolcapone 100 mg by mouth once
• Duloxetine 20 MG
Duloxetine 20 mg by mouth once

Locations

Country	Name	City	State
United States	Robert Wood Johnson University Hospital Somerset	Somerville	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Rutgers, The State University of New Jersey

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Quantitation of microbiome derived metabolism positive drug metabolites in urine	The concentration of microbiome derived metabolism positive drug metabolites in urine will be measured	After a single dose of a microbiome derived metabolism positive drug (over an 8 hour period for each drug)
Other	Quantitation of microbiome derived metabolism positive drugs in urine	The concentration of microbiome derived metabolism positive drugs in urine will be measured.	After a single dose of a microbiome derived metabolism positive drug (over an 8 hour period for each drug)
Primary	Drug area under the plasma concentration versus time curve (AUC)	We will calculate the plasma area under the curve for the microbiome derived metabolism positive probe drugs	After a single dose of a microbiome derived metabolism positive drug (over an 8 hour period for each drug)
Primary	Drug peak plasma concentration	We will measure the peak plasma concentration for microbiome derived metabolism positive probe drugs	After a single dose of a microbiome derived metabolism positive drug (over an 8 hour period for each drug)
Primary	Drug trough plasma concentrations	We will measure the trough plasma concentration for microbiome derived metabolism positive probe drugs	After a single dose of a microbiome derived metabolism positive drug (over an 8 hour period for each drug)
Primary	Drug volume of distribution	We will calculate the volume of distribution for microbiome derived metabolism positive probe drugs	After a single dose of a microbiome derived metabolism positive drug (over an 8 hour period for each drug)
Primary	Drug half-life	We will calculate drug half-life for microbiome derived metabolism positive probe drugs	After a single dose of a microbiome derived metabolism positive drug (over an 8 hour period for each drug)
Primary	Drug plasma clearance	We will calculate drug plasma clearance for each microbiome derived metabolism positive drug.	After a single dose of a microbiome derived metabolism positive drug (over an 8 hour period for each drug)