- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05065671
Microbiome Derived Metabolism and Pharmacokinetics (MDM-PK)
March 18, 2024 updated by: Luigi Brunetti, Rutgers, The State University of New Jersey
Incorporating Drug Metabolism by the Human Gut Microbiome Into Personalized Medicine
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.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Estimated)
14
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Luigi Brunetti, PhD
- Phone Number: 908-595-2645
- Email: luigi.brunetti@rutgers.edu
Study Contact Backup
- Name: Mohamed Donia, PhD
- Phone Number: 609-258-5870
- Email: donia@princeton.edu
Study Locations
-
-
New Jersey
-
Somerville, New Jersey, United States, 08876
- Recruiting
- Robert Wood Johnson University Hospital Somerset
-
Contact:
- Luigi Brunetti, PhD
- Phone Number: 908-595-2645
- Email: luigi.brunetti@rutgers.edu
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Description
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)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Non-Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Tolcapone
Tolcapone 100 mg by mouth once
|
Tolcapone 100 mg by mouth once
|
Experimental: Duloxetine
Duloxetine 20 mg by mouth once
|
Duloxetine 20 mg by mouth once
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Drug area under the plasma concentration versus time curve (AUC)
Time Frame: After a single dose of a microbiome derived metabolism positive drug (over an 8 hour period for each drug)
|
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)
|
Drug peak plasma concentration
Time Frame: After a single dose of a microbiome derived metabolism positive drug (over an 8 hour period for each drug)
|
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)
|
Drug trough plasma concentrations
Time Frame: After a single dose of a microbiome derived metabolism positive drug (over an 8 hour period for each drug)
|
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)
|
Drug volume of distribution
Time Frame: After a single dose of a microbiome derived metabolism positive drug (over an 8 hour period for each drug)
|
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)
|
Drug half-life
Time Frame: After a single dose of a microbiome derived metabolism positive drug (over an 8 hour period for each drug)
|
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)
|
Drug plasma clearance
Time Frame: After a single dose of a microbiome derived metabolism positive drug (over an 8 hour period for each drug)
|
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)
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Quantitation of microbiome derived metabolism positive drug metabolites in urine
Time Frame: After a single dose of a microbiome derived metabolism positive drug (over an 8 hour period for each drug)
|
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)
|
Quantitation of microbiome derived metabolism positive drugs in urine
Time Frame: After a single dose of a microbiome derived metabolism positive drug (over an 8 hour period for each drug)
|
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)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
February 1, 2022
Primary Completion (Estimated)
June 1, 2024
Study Completion (Estimated)
December 31, 2024
Study Registration Dates
First Submitted
September 13, 2021
First Submitted That Met QC Criteria
September 22, 2021
First Posted (Actual)
October 4, 2021
Study Record Updates
Last Update Posted (Actual)
March 20, 2024
Last Update Submitted That Met QC Criteria
March 18, 2024
Last Verified
March 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Disease Attributes
- Infections
- Communicable Diseases
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Psychotropic Drugs
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Antidepressive Agents
- Dopamine Agents
- Serotonin and Noradrenaline Reuptake Inhibitors
- Antiparkinson Agents
- Anti-Dyskinesia Agents
- Catechol O-Methyltransferase Inhibitors
- Duloxetine Hydrochloride
- Tolcapone
Other Study ID Numbers
- Pro2021000945
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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