Clinical trial NCT04590508: A Phase 2 Clinical Trial: Xanthohumol Metabolism and Signature (XMaS) in Crohn's Disease
Official title: A Phase 2 Clinical Trial: Xanthohumol Metabolism and Signature (XMaS) in Crohn's Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Crohn Disease
Keywords: Crohn's Disease
Inflammatory Bowel Disease
IBD
Xanthohumol
Humulus lupulus
Hops
Lead sponsor: National University of Natural Medicine
Sponsor class: OTHER
Collaborators: name: Oregon State University
name: Pacific Northwest National Laboratory
First posted: 2020-10-19
Enrollment: 20
Sex: ALL
Minimum age (years): 21
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized to receive either encapsulated xanthohumol in a rice protein vehicle, or an identical capsule containing vehicle alone.
Primary purpose: TREATMENT

Brief summary: A pilot study to assess the safety and tolerability of an orally administered natural product derived from hops, called xanthohumol, in humans with Crohn's Disease, in order to identify a biological signature of xanthohumol exposure, and to characterize the role of xanthohumol metabolism by intestinal microorganisms in that signature within adults with Crohn's Disease.

Detailed description: This is a double-masked, placebo controlled, randomized clinical trial of xanthohumol, which is a constituent of hops (Humulus lupulus). Hops and its constituents have a long history of use for a variety of conditions. However, knowledge is limited regarding the measurable biological markers of human exposure, and the role of xanthohumol metabolism by microorganisms present in the gut, particularly in individuals with gut pathologies such as Crohn's Disease. This information is necessary for the development of xanthohumol as a potential therapeutic intervention in such conditions.

Eligibility criteria: Inclusion Criteria:

* Adults 21-50 years of age
* Active Crohn's disease not in remission based on a CDAI score \>150
* Willing to take isolated Xanthohumol as a dietary supplement for 8 weeks
* Willing to have blood drawn bi-weekly and fast for 10-12 hours before blood draws
* Willing and able to collect bi-weekly stool samples at home
* Willing and able to collect a 24-hour urine sample before each study visit
* 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)
* For individuals of child-bearing potential, willingness to use an intrauterine device (IUD) or two other concurrent forms of birth control (e.g., 2 of the following categories: condoms, spermicide-containing gels, films or sponges; and/or vaginal rings) to prevent pregnancy while enrolled

Exclusion Criteria:

* Highly variable dosing of anti-inflammatory medications (dose changes more than 1x per week)
* Currently or recent (within last 14 days) taking any dietary supplements containing xanthohumol, flavonoids, or other known "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.
* Consumption of more than 1 beer per day.
* Currently receiving intravenous nutrition support therapy (or within the last 14 days)
* Currently taking anti-coagulant or anti-platelet prescription medications (or they were taken within the last 14 days)
* Currently taking antibiotic, antiparasitic, or antifungal medications orally or intravenously (or they were taken within the last 14 days)
* Initiation of or changes to supplements or medications within 14 days prior to screening.
* Initiation of or changes to an exercise regimen within 14 days prior to screening.
* Initiation of or changes to a food plan within 14 days prior to screening.
* Current involvement or within 14 days prior to screening of a significant diet or weight loss program (such as NutriSystem, Jenny Craig, Atkin's or other low-carb diet programs) or very low-calorie liquid diet programs (such as Optifast, Medifast, and/or HMR)
* Hospitalization (for any reason other than a scheduled medical procedure) within 3 months prior to screening
* Gastrointestinal surgery within 3 months prior to screening
* Malignancy within the last 5 years (with the exception of basal cell carcinoma, squamous cell carcinoma, and/or carcinoma in situ of the cervix)
* Women who are lactating, pregnant or planning pregnancy within the next four months
* 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 the past 14 days.
* Smoking tobacco or nicotine products (combusted or vaporized)
* Use of illicit drugs/substances (such as but not limited to cocaine, phencyclidine (PCP), and methamphetamine) within 14 days of screening
* Use of inhaled or ingested Cannabis products, including Cannabidiol (CBD)
* Currently participating in another interventional research study, or participated in another interventional research study within 14 days of screening
* Do not have an active primary care provider or specialist (i.e., gastroenterologist) managing their CD

Primary outcomes:
measure: Change from Baseline: Aspartate aminotransferase (AST)
timeFrame: 2 weeks, 4 weeks, 6 weeks, and 8 weeks
measure: Change from Baseline:Alanine aminotransferase (ALT)
timeFrame: 2 weeks, 4 weeks, 6 weeks, and 8 weeks
measure: Change from Baseline: gamma-Glutamyl transferase (GGT)
timeFrame: 2 weeks, 4 weeks, 6 weeks, and 8 weeks
measure: Change from Baseline: Estimated glomerular filtration rate
timeFrame: 2 weeks, 4 weeks, 6 weeks, and 8 weeks
measure: Change from Baseline: Blood urea nitrogen to creatinine ratio
timeFrame: 2 weeks, 4 weeks, 6 weeks, and 8 weeks
measure: Change from Baseline: Complete blood count
timeFrame: 2 weeks, 4 weeks, 6 weeks, and 8 weeks
Secondary outcomes:
measure: Change from Baseline: Composite Symptoms: Crohn's Disease Activity Index (CDAI)
timeFrame: 2 weeks, 4 weeks, 6 weeks, and 8 weeks
measure: Change from Baseline: Change in fecal calprotectin levels
timeFrame: 2 weeks, 4 weeks, 6 weeks, and 8 weeks
measure: Change from Baseline: Change in plasma inflammatory markers (pg/mL)
timeFrame: 2 weeks, 4 weeks, 6 weeks, and 8 weeks
Other outcomes:
Locations:
city: Portland
country: United States
facility: National University of Natural Medicine
state: Oregon
Study officials:
affiliation: National University of Natural Medicine
name: Ryan Bradley, ND/MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Langley BO, Ryan JJ, Phipps J, Buttolph L, Bray B, Aslan JE, Metz TO, Stevens JF, Bradley R. 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. Trials. 2022 Oct 22;23(1):885. doi: 10.1186/s13063-022-06782-z.