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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
DOUBLE
Enrollment
30
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.
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.
Helfgott Research Institute National University of Natural Medicine
Portland, Oregon, United States
Change in Plasma Inflammatory Markers
Circulating pro-inflammatory cytokine concentrations (tumor necrosis factor (TNF)-α, 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
Time frame: 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
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.
Time frame: Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
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.
Time frame: Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
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.
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Time frame: Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
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.
Time frame: Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
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.
Time frame: Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
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.
Time frame: 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
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.
Time frame: 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
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.
Time frame: Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks
Estimated Glomerular Filtration Rate
Glomerular filtration rate is estimated based on blood creatinine concentration per standard nephrology practice. Reported as mean change from baseline.
Time frame: 2 weeks, 4 weeks, 6 weeks, and 8 weeks
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.
Time frame: 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
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.
Time frame: 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
Total Red Blood Cell Count
Enumeration of total red blood cell count. Reported as mean change from baseline.
Time frame: Baseline, 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
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.
Time frame: 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
Platelet Count
Enumeration of platelet count. Results are reported as mean change from baseline at weeks 2, 4, 6, and 8.
Time frame: 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
Mean Corpuscular Volume
Enumeration of mean corpuscular volume (MCV). Results are reported as mean change from baseline at weeks 2, 4, 6, and 8.
Time frame: 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
Mean Corpuscular Hemoglobin
Enumeration of mean corpuscular hemoglobin (MCH). Results are reported as mean change from baseline at weeks 2, 4, 6, and 8.
Time frame: 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
Hematocrit
Enumeration of hematocrit. Results are reported as mean change from baseline at weeks 2, 4, 6, and 8.
Time frame: 2 weeks, 4 weeks, 6 weeks, and 8 weeks.