Impact of Probiotics on Drug, Vitamin, and Hormone Metabolism

NCT04281407 | Unknown

• 1 other identifier: STUDY00007095
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Metabolism

Keywords

drug metabolism; CYP3A; UGT; SULT

Outcome Measures

Primary Outcomes (8)

• Oral midazolam peak concentration (Cmax)

  Following 2 mg midazolam syrup given orally at time = 0

  0 to 3 hours on Days 1 and 29

• IV midazolam peak concentration (Cmax)

  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)

  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)

  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)

  500 mg acetaminophen given orally

  0 to 12 hours on Days 1 and 29

• Acetaminophen area under the curve (AUC)

  500 mg acetaminophen given orally at time = 0

  0 to 12 hours on Days 1 and 29

• Acetaminophen-glucuronide area under the curve (AUC)

  500 mg acetaminophen given orally at time = 0

  0 to 12 hours on Days 1 and 29

• Acetaminophen-sulfate area under the curve (AUC)

  500 mg acetaminophen given orally at time = 0

  0 to 12 hours on Days 1 and 29

Secondary Outcomes (5)

• Midazolam terminal half-life

  0 to 12 hours on Days 1 and 29

• Acetaminophen terminal half-life

  0 to 12 hours on Days 1 and 29

• Urinary excretion of 1'-hydroxymidazolam

  0 to 12 hours on Days 1 and 29

• Urinary excretion of acetaminophen-glucuronide

  0 to 12 hours on Days 1 and 29

• Urinary excretion of acetaminophen-sulfate

  0 to 12 hours on Days 1 and 29

Other Outcomes (1)

• Microbiome composition of fecal sample

  Days 1 and 29

Study Arms (1)

Probiotics treatment on midazolam and acetaminophen metabolism

EXPERIMENTAL

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)

Dietary Supplement: Visbiome

Interventions

Visbiome DIETARY_SUPPLEMENT

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

Probiotics treatment on midazolam and acetaminophen metabolism

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Washington: lead

Study Sites (1)

University of Washington

Seattle, Washington, 98195, United States

RECRUITING

Study Officials

• Yvonne Lin, PhD

  University of Washington

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yvonne Lin, PhD

CONTACT

206-616-8728; yvonlin@uw.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor: Department of Pharmaceutics

Model Details: Single arm prospective study

Study Record Dates

• First Submitted: February 11, 2020
• First Posted: February 24, 2020
• Study Start: January 3, 2020
• Primary Completion: June 30, 2020
• Study Completion: August 31, 2020
• Last Updated: February 24, 2020

Record last verified: 2020-02

Locations

US (1)