Clinical trial NCT03735420: Xanthohumol Metabolism and Signature
Official title: Xanthohumol Metabolism and Signature (XMaS) in Healthy Adults
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Healthy
Keywords: xanthohumol
gut microbiome
inflammation
Lead sponsor: National University of Natural Medicine
Sponsor class: OTHER
Collaborators: name: Oregon State University
name: Pacific Northwest National Laboratory
First posted: 2018-11-08
Enrollment: 30
Sex: ALL
Minimum age (years): 21
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
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: OTHER

Brief summary: A pilot study to assess the safety and tolerability of oral xanthohumol in humans, to identify a biological signature of xanthohumol exposure, and to characterize the role of xanthohumol metabolism by intestinal microorganisms in that signature.

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. This information is necessary for the development of xanthohumol as a potential therapeutic intervention in conditions such as inflammatory bowel disease.

Eligibility criteria: Inclusion Criteria:

* Men and Women aged 21-50 years
* Willing to take isolated xanthohumol as a dietary supplement for 8 weeks
* Willing to have blood drawn semi-weekly and to fast for 10-12 hours before blood draws
* Willing and able to collect semi-weekly stool samples at home
* 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)

Exclusion Criteria:

* History of any chronic disease including, but not limited to: diabetes (type 1 or 2); uncontrolled hypertension; coronary artery disease resulting in angina; cardiovascular disease requiring percutaneous coronary intervention (PCI), bypass, or past myocardial infarction or stroke; blood disease including current anemia; cancer (except non-melanoma skin cancer) within the last year or still requiring chemotherapy or hormonal therapy; chronic kidney disease; liver disease including viral hepatitis, non-alcoholic fatty liver disease, or alcoholic hepatitis/cirrhosis; any immunocompromising condition including human immunodeficiency virus/acquired immunodeficiency syndrome or organ transplant requiring anti-rejection medications; chronic osteoarthritis requiring joint replacement or daily use of NSAIDs; chronic endocrine condition including but not limited to: Cushing's, Addison's, Hashimoto's thyroiditis, Grave's disease, etc.
* Body Mass Index (BMI) less than 20 (underweight) or greater than 30 (obese)
* Consumption of more than 1 microbrew beer per day
* 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)
* Use of prescription opioids for any reason within the past 3 months
* Use of prescription corticosteroids for any reason within the past 3 months
* Free of acute viral or bacterial infection, or recent infection within the last 14 days or still requiring prescription medication for treatment
* Free of recent acute trauma occurring within the last 14 days
* Currently or recently (within last 14 days) taking any dietary supplements containing xanthohumol flavonoids, or other known herbal "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.
* Currently receiving intravenous nutrition support therapy (or within the last 30 days)
* Currently taking anti-coagulant or anti-platelet prescription medications (or they were taken within the last 30 days)
* Currently taking antibiotic, antiparasitic, or antifungal medications orally or intravenously (or they were taken within the last 30 days)
* Initiation of or changes to supplements or medications within 30 days prior to screening
* Initiation of or changes to an exercise regimen within 30 days prior to screening
* Initiation of or changes to a food plan within 30 days prior to screening
* Current involvement or within 30 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 an elective medical procedure) within 3 months prior to screening
* Gastrointestinal surgery within 3 months prior to screening
* Undergoing UV therapy (e.g. treatment for skin conditions such as psoriasis).
* Engaging in vigorous exercise more than 6 hours per week.
* 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 28 days
* Use of recreational drugs/substances (such as but not limited to cocaine, phencyclidine (PCP), and methamphetamine) within 30 days of screening
* Currently participating in another interventional research study or participated in another interventional study within 30 days of screening

Primary outcomes:
measure: Change in Plasma Inflammatory Markers
timeFrame: 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
measure: Incidence of Intervention-attributable Adverse Events [Safety and Tolerability]
timeFrame: Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
Secondary outcomes:
measure: Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine
timeFrame: Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
measure: Change in Levels of Metabolic Byproducts of Xanthohumol: Stool
timeFrame: Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
measure: Bile Acids
timeFrame: Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
measure: Gut Inflammation
timeFrame: Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
measure: Aspartate Aminotransferase (AST)
timeFrame: 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
measure: Alanine Aminotransferase (ALT)
timeFrame: 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
measure: Gamma-Glutamyl Transferase (GGT)
timeFrame: Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks
measure: Estimated Glomerular Filtration Rate
timeFrame: 2 weeks, 4 weeks, 6 weeks, and 8 weeks
measure: Blood Urea Nitrogen to Creatinine Ratio
timeFrame: 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
measure: Complete Blood Count Abnormals
timeFrame: 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
measure: Total Red Blood Cell Count
timeFrame: Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
measure: Total White Blood Cell Count
timeFrame: 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
measure: Platelet Count
timeFrame: 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
measure: Mean Corpuscular Volume
timeFrame: 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
measure: Mean Corpuscular Hemoglobin
timeFrame: 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
measure: Hematocrit
timeFrame: 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
Other outcomes:
Locations:
city: Portland
country: United States
facility: Helfgott Research Institute 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: Bradley R, Langley BO, Ryan JJ, Phipps J, Hanes DA, Stack E, Jansson JK, Metz TO, Stevens JF. Xanthohumol microbiome and signature in healthy adults (the XMaS trial): a phase I triple-masked, placebo-controlled clinical trial. Trials. 2020 Oct 7;21(1):835. doi: 10.1186/s13063-020-04769-2.