- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04281407
Impact of Probiotics on Drug, Vitamin, and Hormone Metabolism
Study Overview
Detailed Description
The investigators hypothesize that probiotic treatment (Visbiome) will alter the activities of major classes of drug metabolizing enzymes. Twelve healthy male subjects will participate in a pharmacokinetic study prior to and following supplementation with Visbiome probiotics for 28 days.
The investigators will determine the pharmacokinetics of oral and intravenous midazolam [metabolized by cytochrome P450 3A enzymes, uridine 5'-diphospho-glucuronosyltransferases (UGTs) and sulfotransferase (SULTs)] and acetaminophen (metabolized by UGTs and SULTs), and the circulating concentrations of endogenous compounds (i.e., testosterone and vitamin D metabolites) prior to and following supplementation with Visbiome probiotics for 28 days. In addition, the investigators will compare the fecal microbiota composition and plasma lipidomic and metabolomics profiles to assess the impact of Visbiome supplementation.
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Yvonne Lin, PhD
- Phone Number: 206-616-8728
- Email: yvonlin@uw.edu
Study Locations
-
-
Washington
-
Seattle, Washington, United States, 98195
- Recruiting
- University of Washington
-
Contact:
- Yvonne Lin, PhD
- Phone Number: 206-616-8728
- Email: yvonlin@uw.edu
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Be 18 to 40 years old.
- Biological male participants only with no preference to ethnicity. Women are excluded as one of the aims is to determine the impact of probiotics supplementation on testosterone metabolism. As testosterone and metabolite levels are higher in men than in women, men will be recruited to have an increased ability to detect a difference.
- Have a body mass index between 25 and 3218.5 and 27 kg/m2.
- Be currently in good health without a self-reported history of liver, kidney, gastrointestinal or heart disease, and within the normal range or up to 15% of the upper end of the reference range on the Comprehensive and Hepatic Panel.
- Participants must agree to take 2 capsules of Visbiome, a probiotics supplement provided by the study coordinators, twice a day (morning and evening) from Study Day 2 to 29.
- Participants must agree not to take any prescription drugs for the entire duration of the study. This list includes, but is not restricted to, azole antifungal agents, macrolide antibiotics, anti-seizure medications, antihypertensive agents, cholesterol lowering agents, retinoids, corticosteroids, or immunosuppressant medications for the duration of the study.
- Participants must be willing to avoid ingesting grapefruit, grapefruit juice or other grapefruit juice containing products during the study.
- If an over-the-counter medication is needed, the participant should contact the study coordinator for verification and upon approval, the OTCs can be taken but should not be used 24 hours before each study visit and during the study visits.
- Willing to fast overnight before the pharmacokinetic study days.
- Willing to abstain from alcohol-containing beverages 24 hours before and during the study visits.
Exclusion Criteria:
- Milk allergy or lactose intolerance.
- Currently using prescription medications. Participants may participate in the study following a 2-week washout after discontinuing any prescription medication upon approval of the study team.
- Current cigarette smoker.
- Individuals with systemic disorders affecting the immune system (e.g., HIV, connective tissue disorders, cancers, etc.)
- Self-reported history of liver, kidney, gastrointestinal (e.g., Ulcerative Colitis or Crohn's Disease, intestinal stricture, stenosis, obstruction, fistula, abscess, or ileostomy) or heart disease.
- Abnormal liver or kidney function tests based on the Comprehensive and Hepatic Panel (below the lower end or greater than 15% of the upper end of the reference range).
- Known or suspected history of alcohol or drug abuse.
- Allergic to midazolam, triazolam, diazepam, or lorazepam.
- Recent ingestion (<1 week) of any medication known to be metabolized by CYP3A4 or alter CYP3A activity.
- Unable to give informed consent.
- Participated in another clinical trial or study within 30 days.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Probiotics treatment on midazolam and acetaminophen metabolism
Experimental: Day 1: midazolam (2 mg oral) + acetaminophen (500 mg oral) + midazolam (1 mg IV) Days 1-28: Visbiome (2 capsules) administered BID Day 11: midazolam (2 mg oral) + acetaminophen (500 mg oral) + midazolam (1 mg IV) |
2 capsules of Visbiome, a probiotics supplement, twice a day (morning and evening) for 28 days
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Oral midazolam peak concentration (Cmax)
Time Frame: 0 to 3 hours on Days 1 and 29
|
Following 2 mg midazolam syrup given orally at time = 0
|
0 to 3 hours on Days 1 and 29
|
IV midazolam peak concentration (Cmax)
Time Frame: 3 to 12 hours on Days 1 and 29
|
Following 1 mg midazolam given IV at time = 3 hrs
|
3 to 12 hours on Days 1 and 29
|
Overall midazolam area under the curve (AUC)
Time Frame: 0 to 12 hours on Days 1 and 29
|
Following 2 mg midazolam syrup given orally and 1 mg midazolam given IV
|
0 to 12 hours on Days 1 and 29
|
Overall 1'-hydroxymidazolam area under the curve (AUC)
Time Frame: 0 to 12 hours on Days 1 and 29
|
Following 2 mg midazolam syrup given orally and 1 mg midazolam given IV
|
0 to 12 hours on Days 1 and 29
|
Acetaminophen peak concentration (Cmax)
Time Frame: 0 to 12 hours on Days 1 and 29
|
500 mg acetaminophen given orally
|
0 to 12 hours on Days 1 and 29
|
Acetaminophen area under the curve (AUC)
Time Frame: 0 to 12 hours on Days 1 and 29
|
500 mg acetaminophen given orally at time = 0
|
0 to 12 hours on Days 1 and 29
|
Acetaminophen-glucuronide area under the curve (AUC)
Time Frame: 0 to 12 hours on Days 1 and 29
|
500 mg acetaminophen given orally at time = 0
|
0 to 12 hours on Days 1 and 29
|
Acetaminophen-sulfate area under the curve (AUC)
Time Frame: 0 to 12 hours on Days 1 and 29
|
500 mg acetaminophen given orally at time = 0
|
0 to 12 hours on Days 1 and 29
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Midazolam terminal half-life
Time Frame: 0 to 12 hours on Days 1 and 29
|
Following 2 mg midazolam syrup given orally and 1 mg midazolam given IV
|
0 to 12 hours on Days 1 and 29
|
Acetaminophen terminal half-life
Time Frame: 0 to 12 hours on Days 1 and 29
|
500 mg acetaminophen given orally at time = 0
|
0 to 12 hours on Days 1 and 29
|
Urinary excretion of 1'-hydroxymidazolam
Time Frame: 0 to 12 hours on Days 1 and 29
|
Amount of 1'-hydroxymidazolam recovered in urine
|
0 to 12 hours on Days 1 and 29
|
Urinary excretion of acetaminophen-glucuronide
Time Frame: 0 to 12 hours on Days 1 and 29
|
Amount of acetaminophen-glucuronide recovered in urine
|
0 to 12 hours on Days 1 and 29
|
Urinary excretion of acetaminophen-sulfate
Time Frame: 0 to 12 hours on Days 1 and 29
|
Amount of acetaminophen-sulfate recovered in urine
|
0 to 12 hours on Days 1 and 29
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Microbiome composition of fecal sample
Time Frame: Days 1 and 29
|
Compositional studies using sequencing of 16S gene
|
Days 1 and 29
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Yvonne Lin, PhD, University of Washington
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- STUDY00007095
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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