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Xanthohumol microbiome and signature in adults with Crohn’s disease (the XMaS trial): a protocol for a phase II triple-masked, placebo-controlled clinical trial

Journal Article · · Trials
 [1];  [2];  [2];  [2];  [2];  [3];  [4];  [5];  [6]
  1. National University of Natural Medicine (NUNM), Portland, OR (United States); University of Washington, Seattle, WA (United States)
  2. National University of Natural Medicine (NUNM), Portland, OR (United States)
  3. Oregon Health and Science University, Portland, OR (United States)
  4. Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
  5. Oregon State University, Corvallis, OR (United States)
  6. National University of Natural Medicine (NUNM), Portland, OR (United States); University of California, San Diego, La Jolla, CA (United States)
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Xanthohumol (XN), a bioactive flavonoid from Humulus lupulus with anti-inflammatory properties, has potential benefits for patients with Crohn’s disease (CD), a type of inflammatory bowel disease. We recently completed and published results of a placebo-controlled phase I clinical trial demonstrating the safety and tolerability of 24 mg XN daily for 8 weeks. The present study aims to evaluate the safety and tolerability of the same dose of XN adults with clinically active CD in a placebo-controlled phase II clinical trial. Additional aims will assess the impact of XN on inflammatory biomarkers, platelet function, CD clinical activity, and stool microbial composition. The metabolism of XN will also be evaluated. This article provides a model protocol for consideration in investigations of XN or other natural products in disease states. A triple-masked, randomized, placebo-controlled trial will be conducted in adults with clinically active CD. Participants (n ≤ 32) will be randomized to either 24 mg encapsulated XN per day or placebo and followed for 8 weeks. Throughout the trial, participants will be queried for adverse events. Biomarkers of clinical safety, blood and stool markers of inflammation, platelet function, Crohn’s Disease Activity Index score, stool microbial composition, and XN metabolite profiles in blood, urine, and stool will be assessed every 2 weeks. We describe the protocol for a phase II clinical trial that evaluates the safety and tolerability of XN in adults with active CD, as well as evaluate metabolism and mechanisms that are relevant to CD and other diseases with underlying inflammation and/or gut permeability. The effects of XN on inflammatory biomarkers, platelet function, the microbiota, and multi-omics biomarkers measured in this phase II trial of adults with CD will be compared to the effects of XN in healthy adults in our previous phase I trial. The results of the study will advance the evidence guiding the use of XN in patients with CD.

Research Organization:
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
AC05-76RL01830
OSTI ID:
2469848
Journal Information:
Trials, Journal Name: Trials Journal Issue: 1 Vol. 23; ISSN 1745-6215
Publisher:
BioMed CentralCopyright Statement
Country of Publication:
United States
Language:
English

References (36)

Serum lipopolysaccharide-binding protein in endotoxemic patients with inflammatory bowel disease journal March 2007
A safety study of oral xanthohumol administration and its influence on fertility in Sprague Dawley rats journal September 2005
Xanthohumol, a new all-rounder? journal September 2005
Human pharmacokinetics of xanthohumol, an antihyperglycemic flavonoid from hops journal August 2013
Reductive Metabolism of Xanthohumol and 8‐Prenylnaringenin by the Intestinal Bacterium Eubacterium ramulus journal December 2018
Improvements in Metabolic Syndrome by Xanthohumol Derivatives Are Linked to Altered Gut Microbiota and Bile Acid Metabolism journal December 2019
Xanthohumol Microbiome and Signature in Healthy Adults (the XMaS Trial): Safety and Tolerability Results of a Phase I Triple‐Masked, Placebo‐Controlled Clinical Trial journal March 2021
The chemistry of gut microbial metabolism of polyphenols journal March 2016
Quantitative analysis of xanthohumol and related prenylflavonoids in hops and beer by liquid chromatography–tandem mass spectrometry journal January 1999
Conformational modulation of the farnesoid X receptor by prenylflavonoids: Insights from hydrogen deuterium exchange mass spectrometry (HDX-MS), fluorescence titration and molecular docking studies journal December 2016
Xanthohumol, the chalcone from beer hops (Humulus lupulus L.), is the ligand for farnesoid X receptor and ameliorates lipid and glucose metabolism in KK-A mice journal October 2005
Daily Sampling Reveals Personalized Diet-Microbiome Associations in Humans journal June 2019
Safety Versus Tolerability journal May 2018
The socio-economic implications of the coronavirus pandemic (COVID-19): A review journal June 2020
Research electronic data capture (REDCap)—A metadata-driven methodology and workflow process for providing translational research informatics support journal April 2009
The REDCap consortium: Building an international community of software platform partners journal July 2019
PROMIS measures of pain, fatigue, negative affect, physical function, and social function demonstrated clinical validity across a range of chronic conditions journal May 2016
Xanthohumol and related prenylflavonoids from hops and beer: to your good health! journal May 2004
Xanthohumol lowers body weight and fasting plasma glucose in obese male Zucker fa/fa rats journal July 2013
Xanthohumol induces phase II enzymes via Nrf2 in human hepatocytes in vitro journal February 2013
Natural products in drug discovery: advances and opportunities journal January 2021
Impact of specific functional groups in flavonoids on the modulation of platelet activation journal June 2018
A review of activity indices and efficacy endpoints for clinical trials of medical therapy in adults with Crohn's disease journal February 2002
Hypercoagulability and Platelet Abnormalities in Inflammatory Bowel Disease journal August 2015
Combined Plasma Elevation of CRP, Intestinal-Type Fatty Acid-Binding Protein (I-FABP), and sCD14 Identify Older Patients at High Risk for Health Care-Associated Infections journal June 2017
Correlation of Stool Frequency and Abdominal Pain Measures With Simple Endoscopic Score for Crohn’s Disease journal October 2019
Mechanisms of the antiangiogenic activity by the hop flavonoid xanthohumol: NF‐κB and Akt as targets journal December 2005
Improving natural product research translation: From source to clinical trial journal December 2019
Xanthohumol inhibits angiogenesis by suppressing nuclear factor-κB activation in pancreatic cancer journal December 2017
Antileukemia effects of xanthohumol in Bcr/Abl-transformed cells involve nuclear factor- B and p53 modulation journal September 2008
Increased Intestinal Permeability and Decreased Barrier Function: Does It Really Influence the Risk of Inflammation? journal January 2016
Phosphoproteomic quantitation and causal analysis reveal pathways in GPVI/ITAM-mediated platelet activation programs journal November 2020
Standardization and reference ranges for whole blood platelet function measurements using a flow cytometric platelet activation test journal February 2018
Increase in Plasma Endotoxin Concentrations and the Expression of Toll-Like Receptors and Suppressor of Cytokine Signaling-3 in Mononuclear Cells After a High-Fat, High-Carbohydrate Meal journal September 2009
Xanthohumol ameliorates Diet-Induced Liver Dysfunction via Farnesoid X Receptor-Dependent and Independent Signaling journal April 2021
Composition of the Gut Microbiome Influences Production of Sulforaphane-Nitrile and Iberin-Nitrile from Glucosinolates in Broccoli Sprouts journal August 2021

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60 APPLIED LIFE SCIENCES
Crohn’s disease
Inflammation
Inflammatory bowel disease
Microbiome
Natural product
Randomized controlled trial
Research & Experimental Medicine
Safety
Tolerability
Xanthohumol