TitleXanthohumol microbiome and signature in adults with Crohn's disease (the XMaS trial): a protocol for a phase II triple-masked, placebo-controlled clinical trial.
Publication TypeJournal Article
Year of Publication2022
AuthorsLangley BO, Ryan JJoan, Phipps J, Buttolph L, Bray B, Aslan JE, Metz TO, Stevens JF, Bradley R
Date Published2022 Oct 22
KeywordsAdult, Biological Products, Biomarkers, Clinical Trials, Phase II as Topic, Crohn Disease, Flavonoids, Humans, Inflammation, Microbiota, Randomized Controlled Trials as Topic

BACKGROUND: 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.

METHODS: 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.

DISCUSSION: 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.

TRIAL REGISTRATION: ClinialTrials.gov NCT04590508. Registered on October 19, 2020.

Alternate JournalTrials
PubMed ID36273173
PubMed Central IDPMC9587656
Grant ListL30 HL143718 / HL / NHLBI NIH HHS / United States
1R01AT010271-01 / AT / NCCIH NIH HHS / United States
R01 HL146549 / HL / NHLBI NIH HHS / United States
R90 AT008924 / AT / NCCIH NIH HHS / United States
T90 AT008544 / AT / NCCIH NIH HHS / United States
R01HL146549 / HL / NHLBI NIH HHS / United States
K24 AT011568 / AT / NCCIH NIH HHS / United States