Impact of Probiotics on Drug, Vitamin, and Hormone Metabolism

NCT ID: NCT04281407

Last Updated: 2020-02-24

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-03
• Study Completion Date: 2020-08-31

Brief Summary

This is an open-label, fixed sequence study of the effect of probiotics supplementation on drug, vitamin, and hormone metabolism.

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.

Conditions

Metabolism

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

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)

Group Type: EXPERIMENTAL

Visbiome

Intervention Type: DIETARY_SUPPLEMENT

2 capsules of Visbiome, a probiotics supplement, twice a day (morning and evening) for 28 days

Interventions

Visbiome

2 capsules of Visbiome, a probiotics supplement, twice a day (morning and evening) for 28 days

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

University of Washington

OTHER

Sponsor Role: lead

Responsible Party

Yvonne Lin

Associate Professor: Department of Pharmaceutics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yvonne Lin, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Washington

Locations

University of Washington

Seattle, Washington, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Yvonne Lin, PhD

Role: CONTACT

yvonlin@uw.edu

206-616-8728

Facility Contacts

Yvonne Lin, PhD

Role: primary

yvonlin@uw.edu

206-616-8728

Other Identifiers

STUDY00007095

Identifier Type: -

Identifier Source: org_study_id