Xanthohumol Metabolism and Signature

Healthy Clinical Trial

— XMaS  

Official title:

Xanthohumol Metabolism and Signature (XMaS) in Healthy Adults

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03735420
• Other study ID #: RB9718
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: August 12, 2019
• Est. completion date: December 31, 2024

Study information

• Verified date: July 2023
• Source: National University of Natural Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 30
• Est. completion date: December 31, 2024
• Est. primary completion date: May 7, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Xanthohumol
The xanthohumol supplement will be administered in a capsule. Participants in the experimental arm will consume the capsule once per day, with the first meal. The intervention will extend for 8 weeks.
• Placebo oral capsule
The placebo (vehicle) will be administered in a capsule. Participants in the placebo arm will consume the capsule once per day, with the first meal.

Locations

Country	Name	City	State
United States	Helfgott Research Institute National University of Natural Medicine	Portland	Oregon

Sponsors (3)

Lead Sponsor	Collaborator
National University of Natural Medicine	Oregon State University, Pacific Northwest National Laboratory

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Plasma Inflammatory Markers	Circulating pro-inflammatory cytokine concentrations (tumor necrosis factor (TNF)-a, interleukin (IL)-1 beta, IL-6, IL-8, IL-10, and IL-12p70), will be measured simultaneously with a flow cytometry-based multiplex assay. The measures were assessed at Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks; weeks 2, 4, 6, and 8 reported	2 weeks, 4 weeks, 6 weeks, and 8 weeks.
Primary	Incidence of Intervention-attributable Adverse Events [Safety and Tolerability]	Self-reported adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events. Reported as: New onset "FDA serious" adverse events (Grade 1); New onset "moderate" adverse events (Grade 2). The measures were assessed at Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks; weeks 2, 4, 6, and 8 reported.	Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
Secondary	Change in Levels of Metabolic Byproducts of Xanthohumol: Plasma and Urine	Xanthohumol and xanthohumol metabolites in blood, urine and stool, will be measured by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Metabolites include 6-prenylnaringenin (6-PN), 8-prenylnaringenin (8-PN), dihydroxanthohumol (DXN), desmethyldihydroxanthohumol (DDXN), isoxanthohumol (IXN), and xanthohumol (XN). The measures were assessed at Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks; baseline, weeks 2, 4, 6, and 8 reported for urine and plasma.	Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
Secondary	Change in Levels of Metabolic Byproducts of Xanthohumol: Stool	Xanthohumol and xanthohumol metabolites in blood, urine and stool, will be measured by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Metabolites include 6-prenylnaringenin (6-PN), 8-prenylnaringenin (8-PN), dihydroxanthohumol (DXN), desmethyldihydroxanthohumol (DDXN), isoxanthohumol (IXN), and xanthohumol (XN). The measures were assessed at Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks; baseline, weeks 2, 4, 6, and 8 reported for urine and plasma. As stool metabolites have not yet been analyzed, data will be released upon assessment.	Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
Secondary	Bile Acids	Bile acid concentrations in blood and feces, will be measured by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry, and expressed as mean change over time from baseline.	Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
Secondary	Gut Inflammation	Fecal calprotectin, a protein associated with gut inflammation and irritable gut syndrome, will be measured by enzyme-linked immunosorbent assay, and expressed as mean change over time from baseline.	Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
Secondary	Aspartate Aminotransferase (AST)	Aspartate aminotransferase is an enzyme that is often measured in blood as an indication of liver toxicity. Reported as mean change from baseline.	2 weeks, 4 weeks, 6 weeks, and 8 weeks.
Secondary	Alanine Aminotransferase (ALT)	Alanine aminotransferase is an enzyme that is often measured in blood as an indication of liver toxicity. Reported as mean change from baseline.	2 weeks, 4 weeks, 6 weeks, and 8 weeks.
Secondary	Gamma-Glutamyl Transferase (GGT)	Gamma-glutamyl transferase is an enzyme that is often measured in blood as an indication of liver toxicity. Reported as mean change from baseline.	Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks
Secondary	Estimated Glomerular Filtration Rate	Glomerular filtration rate is estimated based on blood creatinine concentration per standard nephrology practice. Reported as mean change from baseline.	2 weeks, 4 weeks, 6 weeks, and 8 weeks
Secondary	Blood Urea Nitrogen to Creatinine Ratio	Blood urea nitrogen (BUN) : creatinine (Cr) is a ratio of serum concentrations of two compounds associated with renal function. Reported as mean change from baseline.	2 weeks, 4 weeks, 6 weeks, and 8 weeks.
Secondary	Complete Blood Count Abnormals	Enumeration of the various subtypes of blood cells (i.e., red blood cells, white blood cells, and platelets), plus indices including mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), and hematocrit. Reported as: % abnormal (i.e., number of participants with an abnormal value compared to the number of participants in the group) and % new abnormals if abnormal counts were noted. Abnormality is assessed according to standards for age and sex measurements under Quest Diagnostics criteria.	2 weeks, 4 weeks, 6 weeks, and 8 weeks.
Secondary	Total Red Blood Cell Count	Enumeration of total red blood cell count. Reported as mean change from baseline.	Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
Secondary	Total White Blood Cell Count	Enumeration of total white blood cell count. Results are reported as mean change from baseline at weeks 2, 4, 6, and 8.	2 weeks, 4 weeks, 6 weeks, and 8 weeks.
Secondary	Platelet Count	Enumeration of platelet count. Results are reported as mean change from baseline at weeks 2, 4, 6, and 8.	2 weeks, 4 weeks, 6 weeks, and 8 weeks.
Secondary	Mean Corpuscular Volume	Enumeration of mean corpuscular volume (MCV). Results are reported as mean change from baseline at weeks 2, 4, 6, and 8.	2 weeks, 4 weeks, 6 weeks, and 8 weeks.
Secondary	Mean Corpuscular Hemoglobin	Enumeration of mean corpuscular hemoglobin (MCH). Results are reported as mean change from baseline at weeks 2, 4, 6, and 8.	2 weeks, 4 weeks, 6 weeks, and 8 weeks.
Secondary	Hematocrit	Enumeration of hematocrit. Results are reported as mean change from baseline at weeks 2, 4, 6, and 8.	2 weeks, 4 weeks, 6 weeks, and 8 weeks.