Administrative information
Title {1}
|
Xanthohumol Microbiome and Signature in Healthy Adults (the XMaS Trial): A Phase I Triple-masked, Placebo-controlled Clinical Trial
|
Trial registration {2a and 2b}.
| ClinicalTrials.gov (NCT03735420) and posted on November 8th, 2018 All items per WHO trial registration requirements can be found within the body of the protocol. |
Protocol version {3}
| Version 1.8 11/21/2019 |
Funding {4}
| • National Center for Complementary and Integrative Health (NCCIH): Grants 1RO1AT010271-01, R01 AT010271-02S1 • Hopsteiner, Inc.: XanthoFlav Pure product • Metagenics, Inc.: Xanthohumol and placebo capsules |
Author details {5a}
| Drs. Bradley, Stevens, Ryan, and Phipps have previously received grant support and study product donations from Metagenics, Inc. which supported the phase I XMaS study by encapsulating the test materials used in this trial. |
Name and contact information for the trial sponsor {5b}
| Yisong Wang, Program Director, NCCIH
yisong.wang@nih.gov
|
Role of sponsor {5c}
| This trial is an investigator-initiated and NUNM-sponsored clinical trial funded by the NCCIH of the National Institutes of Health (NIH). The NIH and associated reviewers provided feedback on trial participation criteria which were incorporated into the trial protocol, as was necessary to secure NIH approval to recruit. The NIH did not influence the conduct, analysis, writing or decision to submit the protocol for publication. Although encapsulation of the study product was provided by Metagenics, Inc., employees of Metagenics, Inc. did not have any involvement in the study design, collection of data, or manuscript development. Funders will not be involved in data analysis, interpretation, or future manuscript development. None of the authors hold stock in Metagenics, Inc. or its parent company and have no direct financial ties to the outcome of the proposed clinical research. |
Submission Deadline
| This trial has not reached maximum enrollment to date, March 24, 2020. Although the trial is nearing the final stages prior to completion, there was insufficient time for the study team to complete a protocol manuscript until Dr. Langley was fully trained on and incorporated into the trial’s operations. We respectfully submit this protocol manuscript on March 24, 2020. |
Introduction
Background and rationale {6a}
Transcription factor | Xanthohumol mechanisms | Pertinent clinical conditions |
---|---|---|
Farnesoid X receptor (FXR) | FXR agonist in vitro and in vivo | • Type 2 diabetes mellitus • Metabolic syndrome • Dyslipidemia • Obesity • Non-alcoholic fatty liver disease • Non-alcoholic steato-hepatitis • Cholelithiasis • Inflammatory bowel disease • Cancer |
Nuclear factor-kappa B (NFkB) | Inhibits activation of NFkB in vitro and in vivo | • Inflammatory bowel disease • Rheumatic disease • Asthma • Autoimmunity • Cancer |
Nuclear factor erythroid 2-related factor 2 (NRF2) | Increases expression of and activation of NRF2 in vitro | • Autoimmunity • Alzheimer’s disease • Inflammatory bowel disease • Cancer |
Methods/design
Objectives {7}
Aim | Marker | Assessment method |
---|---|---|
1. Safety & Tolerability | a. RBC, WBC, platelets b. eGFR, electrolytes, BUN:Cr, AST, ALT, GGT, alkaline phosphatase, bilirubin c. Adverse events, quality of life | a. Complete Blood Count (CBC) b. Comprehensive Metabolic Panel (CMP) c. Adverse Events Questionnaire, PROMIS-29 |
2. Inflammation | a. Inflammatory cytokines: IL-1β, IL-2, IL-6, IL-8, IL-10, TNF-α, and IL-12p70 b. Fecal calprotectin | a. Serum or plasma analysis b. Stool analysis |
3a. Gut Permeability | a. CD14, lipopolysaccharide binding protein, intestinal fatty acid binding protein | a. Plasma analysis |
3b. Xanthohumol Metabolism | a. Xanthohumol metabolite profiles | a. 24-hour urinalysis, plasma analysis, stool analysis |
3c. Microbial Composition Changes | a. Metagenomic DNA sequencing and taxonomic profiling b. Proteomic characterization | a. Compared to xanthohumol metabolite profiles b. Activity-based proteomic assay |
Hypotheses
Trial design {8}
Materials and methods
Study setting {9}
Eligibility criteria {10}
Inclusion criteria | Exclusion criteria |
---|---|
• Males and females aged 21–50 years • BMI 20–30 • Willing to be randomized to take isolated xanthohumol as a dietary supplement (or placebo) for 8 weeks • Willing to have blood drawn every 2 weeks and fast for 10–12 h before blood draws • Willing and able to collect stool samples at home every 2 weeks • 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) Permitted concomitant care or intervention during the trial: • Use of over-the-counter medications as indicated on the label • Multi-vitamin/multi-mineral products • Dietary supplements except as detailed in exclusion criteria | • History of any chronic disease • Consumption of more than 1 microbrew beer per day • Typical intake of more than 2 alcohol-containing beverages per day, more than 14 per week, or more than 4 in any single day within 28 days prior to screening • 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) • Acute viral or bacterial infection, or recent infection within 14 days prior to screening or still requiring prescription medication for treatment • Engaging in vigorous exercise more than 6 h per week • Women who are lactating, pregnant, or planning pregnancy during the study period • Within 3 months of screening: ° Use of prescription opioids for any reason ° Use of prescription corticosteroids for any reason ° Hospitalization (for any reason other than an elective medical procedure) ° Gastrointestinal surgery • Current or within 30 days of screening: ° Intravenous nutrition support therapy ° Intake of anti-coagulant or anti-platelet prescription medications ° Intake of antibiotic, antiparasitic, or antifungal medications orally or intravenously ° Initiation of or changes to supplements or medications, an exercise regimen, or food plan ° Involvement in a significant diet or weight loss program, low-carb diet program, or very-low calorie liquid diet program ° Use of recreational drugs/substances ° Participation in another interventional research study ° Undergoing UV therapy • Within 14 days of screening: ° Recent acute trauma occurring within 14 days prior to screening ° Recent (within 14 days prior to screening) intake of any dietary supplements containing xanthohumol flavonoids, or other natural products typically taken to modulate inflammation including curcumin, turmeric, fenugreek, hops, rosemary, ginger, white willow, devil’s claw, fish oil (doses > 1 g/day), bioflavonoids, or quercetin |