TY - JOUR
T1 - Xanthohumol microbiome and signature in adults with Crohn’s disease (the XMaS trial)
T2 - a protocol for a phase II triple-masked, placebo-controlled clinical trial
AU - Langley, Blake O.
AU - Ryan, Jennifer Joan
AU - Phipps, John
AU - Buttolph, Lita
AU - Bray, Brenna
AU - Aslan, Joseph E.
AU - Metz, Thomas O.
AU - Stevens, Jan F.
AU - Bradley, Ryan
N1 - Funding Information:
The XMaS trial received funding from the National Institutes of Health, National Center for Complementary and Integrative Medicine (R01 AT010271, R01 AT010271-02S1, and K24AT011568), and National Heart, Lung, and Blood Institute (R01 HL146549 and its supplement 02S1). Pacific Northwest National Laboratory is a multi-program national laboratory operated by Battelle for the US Department of Energy under contract DE-AC05-76RL01830. Study products were produced by Hopsteiner and Metagenics, Inc. Neither company was involved in the research design, data analysis, or interpretation.
Funding Information:
We thank Ms. Emily Stack for her diligence in supporting the trial development and initiation. We also thank Hopsteiner for providing and ensuring the quality of the xanthohumol raw material and Metagenics, Inc. and its Product Development team for providing the rice protein matrix and for encapsulating the study drug.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
KW - Crohn’s disease
KW - Inflammation
KW - Inflammatory bowel disease
KW - Microbiome
KW - Natural product
KW - Randomized controlled trial
KW - Safety
KW - Tolerability
KW - Xanthohumol
UR - http://www.scopus.com/inward/record.url?scp=85140314378&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85140314378&partnerID=8YFLogxK
U2 - 10.1186/s13063-022-06782-z
DO - 10.1186/s13063-022-06782-z
M3 - Article
C2 - 36273173
AN - SCOPUS:85140314378
SN - 1745-6215
VL - 23
JO - Trials
JF - Trials
IS - 1
M1 - 885
ER -