Xanthohumol Metabolism and Signature

NCT03735420 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 1 other identifier: RB9718
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

A pilot study to assess the safety and tolerability of oral xanthohumol in humans, to identify a biological signature of xanthohumol exposure, and to characterize the role of xanthohumol metabolism by intestinal microorganisms in that signature.

Conditions

Healthy

Keywords

xanthohumol; gut microbiome; inflammation

Outcome Measures

Primary Outcomes (2)

• Change in Plasma Inflammatory Markers

  Circulating pro-inflammatory cytokine concentrations (tumor necrosis factor (TNF)-α, interleukin (IL)-1 beta, IL-6, IL-8, IL-10, and IL-12p70), will be measured simultaneously with a flow cytometry-based multiplex assay. The measures were assessed at Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks; weeks 2, 4, 6, and 8 reported

  2 weeks, 4 weeks, 6 weeks, and 8 weeks.

• Incidence of Intervention-attributable Adverse Events [Safety and Tolerability]

  Self-reported adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events. Reported as: New onset "FDA serious" adverse events (Grade 1); New onset "moderate" adverse events (Grade 2). The measures were assessed at Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks; weeks 2, 4, 6, and 8 reported.

  Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks.

Secondary Outcomes (16)

• Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine

  Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks.

• Change in Levels of Metabolic Byproducts of Xanthohumol: Stool

  Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks.

• Bile Acids

  Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks.

• Gut Inflammation

  Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks.

• Aspartate Aminotransferase (AST)

  2 weeks, 4 weeks, 6 weeks, and 8 weeks.

Study Arms (2)

Xanthohumol

EXPERIMENTAL

Participants will receive 24 mg of 98% pure xanthohumol in a rice protein vehicle by mouth once daily with the first daily meal.

Drug: Xanthohumol

Placebo oral capsule

PLACEBO COMPARATOR

Participants will receive vehicle (rice protein) by mouth once daily with the first daily meal.

Drug: Placebo oral capsule

Interventions

Xanthohumol DRUG

The xanthohumol supplement will be administered in a capsule. Participants in the experimental arm will consume the capsule once per day, with the first meal. The intervention will extend for 8 weeks.

Xanthohumol

Placebo oral capsule DRUG

The placebo (vehicle) will be administered in a capsule. Participants in the placebo arm will consume the capsule once per day, with the first meal.

Also known as: Vehicle

Placebo oral capsule

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Men and Women aged 21-50 years
• Willing to take isolated xanthohumol as a dietary supplement for 8 weeks
• Willing to have blood drawn semi-weekly and to fast for 10-12 hours before blood draws
• Willing and able to collect semi-weekly stool samples at home
• Able to speak, read, and understand English
• Must be able to provide written informed consent
• Non-smokers (including tobacco and Cannabis products, combusted or vaporized)

You may not qualify if:

• History of any chronic disease including, but not limited to: diabetes (type 1 or 2); uncontrolled hypertension; coronary artery disease resulting in angina; cardiovascular disease requiring percutaneous coronary intervention (PCI), bypass, or past myocardial infarction or stroke; blood disease including current anemia; cancer (except non-melanoma skin cancer) within the last year or still requiring chemotherapy or hormonal therapy; chronic kidney disease; liver disease including viral hepatitis, non-alcoholic fatty liver disease, or alcoholic hepatitis/cirrhosis; any immunocompromising condition including human immunodeficiency virus/acquired immunodeficiency syndrome or organ transplant requiring anti-rejection medications; chronic osteoarthritis requiring joint replacement or daily use of NSAIDs; chronic endocrine condition including but not limited to: Cushing's, Addison's, Hashimoto's thyroiditis, Grave's disease, etc.
• Body Mass Index (BMI) less than 20 (underweight) or greater than 30 (obese)
• Consumption of more than 1 microbrew beer per day
• Use of NSAIDs more than once per week for headaches, routine aches/pains, etc.
• Use of any prescription drugs, including oral contraceptives (due to potential interference with mechanisms under investigation)
• Use of prescription opioids for any reason within the past 3 months
• Use of prescription corticosteroids for any reason within the past 3 months
• Free of acute viral or bacterial infection, or recent infection within the last 14 days or still requiring prescription medication for treatment
• Free of recent acute trauma occurring within the last 14 days
• Currently or recently (within last 14 days) taking any dietary supplements containing xanthohumol flavonoids, or other known herbal "anti-inflammatories" including: curcumin, turmeric, fenugreek, hops, rosemary, ginger, white willow, Devil's claw, fish oil (doses\>1 g/day), or quercetin. Candidates will be given the option to "wash out" for 14 days and re-contact the study team.
• Currently receiving intravenous nutrition support therapy (or within the last 30 days)
• Currently taking anti-coagulant or anti-platelet prescription medications (or they were taken within the last 30 days)
• Currently taking antibiotic, antiparasitic, or antifungal medications orally or intravenously (or they were taken within the last 30 days)
• Initiation of or changes to supplements or medications within 30 days prior to screening
• Initiation of or changes to an exercise regimen within 30 days prior to screening

Sponsors & Collaborators

• National University of Natural Medicine: lead
• Oregon State University: collaborator
• Pacific Northwest National Laboratory: collaborator

Study Sites (1)

Helfgott Research Institute National University of Natural Medicine

Portland, Oregon, 97201, United States

Location

Related Publications (2)

• Jamieson PE, Smart EB, Bouranis JA, Choi J, Danczak RE, Wong CP, Paraiso IL, Maier CS, Ho E, Sharpton TJ, Metz TO, Bradley R, Stevens JF. Gut enterotype-dependent modulation of gut microbiota and their metabolism in response to xanthohumol supplementation in healthy adults. Gut Microbes. 2024 Jan-Dec;16(1):2315633. doi: 10.1080/19490976.2024.2315633. Epub 2024 Feb 15.

  PMID: 38358253 DERIVED

• Bradley R, Langley BO, Ryan JJ, Phipps J, Hanes DA, Stack E, Jansson JK, Metz TO, Stevens JF. Xanthohumol microbiome and signature in healthy adults (the XMaS trial): a phase I triple-masked, placebo-controlled clinical trial. Trials. 2020 Oct 7;21(1):835. doi: 10.1186/s13063-020-04769-2.

  PMID: 33028396 DERIVED

MeSH Terms

Conditions

Inflammation

Interventions

xanthohumol

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Ryan Bradley, ND, MPH
• Organization: National University of Natural Medicine

rbradley@nunm.edu

5035521862

Study Officials

• Ryan Bradley, ND, MPH

  National University of Natural Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Randomization will occur in up to 8 blocks of 4 based on biological sex. Initial randomization series will be generated using readily available random sequence generators designed to do so. A series of sequential envelopes will be generated, each containing the allocation for one participant. Envelopes will be opaque and signed across the seal. The randomization "code" will be kept in a sealed envelope with a signature across the label and dated the day of creation. Study product and comparator (placebo) will be compounded and placed in identical opaque capsules outside the institution.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Helfgott Research Institute

Model Details: Participants will be randomized to receive either encapsulated xanthohumol in a rice protein vehicle, or an identical capsule containing vehicle alone.

Study Record Dates

• First Submitted: October 11, 2018
• First Posted: November 8, 2018
• Study Start: August 12, 2019
• Primary Completion: May 7, 2020
• Study Completion: December 31, 2024
• Last Updated: August 27, 2024
• Results First Posted: January 11, 2022

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Time Frame: We will share our data no later than on acceptance of the first publication of the findings from the respective data set(s).
• Access Criteria: All indicated repositories are freely available to the research community.

Locations

US (1)