A Phase 2 Clinical Trial: Xanthohumol Metabolism and Signature (XMaS) in Crohn's Disease

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 2 Clinical Trial: Xanthohumol Metabolism and Signature (XMaS) in Crohn's Disease

Conditions
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Crohn Disease

Intervention / Treatment
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* Drug: Xanthohumol
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomized to receive either encapsulated xanthohumol in a rice protein vehicle, or an identical capsule containing vehicle alone.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Xanthohumol<br>Participants will take capsules containing 24 mg of xanthohumol in a rice protein vehicle by mouth once daily with the first daily meal. | Drug: Xanthohumol<br>* The xanthohumol supplement will be administered in a capsule and taken orally.<br>|
| Placebo Comparator: Placebo<br>Participants will receive capsules filled with a rice protein vehicle by mouth once daily with the first daily meal. | Other: Placebo<br>* The placebo will be administered in a capsule and taken orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline: Aspartate aminotransferase (AST) | Aspartate aminotransferase is an enzyme that is often measured in blood as an indication of liver toxicity. Reported as: % abnormal, % new abnormals, and mean change from baseline. | 2 weeks, 4 weeks, 6 weeks, and 8 weeks | 
| Change from Baseline:Alanine aminotransferase (ALT) | Alanine aminotransferase is an enzyme that is often measured in blood as an indication of liver toxicity. Reported as: % abnormal, % new abnormals, and mean change from baseline. | 2 weeks, 4 weeks, 6 weeks, and 8 weeks | 
| Change from Baseline: gamma-Glutamyl transferase (GGT) | Gamma-glutamyl transferase is an enzyme that is often measured in blood as an indication of liver toxicity. Reported as: % abnormal, % new abnormals, and mean change from baseline. | 2 weeks, 4 weeks, 6 weeks, and 8 weeks | 
| Change from Baseline: Estimated glomerular filtration rate | Glomerular filtration rate is estimated based on blood creatinine concentration per standard nephrology practice. Reported as: % abnormal, % new abnormals, and mean change from baseline. | 2 weeks, 4 weeks, 6 weeks, and 8 weeks | 
| Change from Baseline: Blood urea nitrogen to creatinine ratio | Blood urea nitrogen:creatinine is a ratio of serum concentrations of two compounds associated with renal function. Reported as: % abnormal, % new abnormals, and mean change from baseline. | 2 weeks, 4 weeks, 6 weeks, and 8 weeks | 
| Change from Baseline: Complete blood count | 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 hemocrit. Reported as: % abnormal, % new abnormals, and mean change from baseline. | 2 weeks, 4 weeks, 6 weeks, and 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline: Composite Symptoms: Crohn's Disease Activity Index (CDAI) | The Crohn's Disease Activity Index or CDAI is frequently used to assess disease severity. It gives a score ranging from 0 to over 600, based on a diary of symptoms kept by the patient for 7 days, and other measurements such as the patient's weight and haematocrit. A CDAI score of less than 150 is considered to be remission, a score greater than 220 is considered to define moderate to severe disease, and a score greater than 300 is considered to be severe disease. Most major research studies on medications in Crohn's disease define response as a fall of the CDAI of greater than 70 points. | 2 weeks, 4 weeks, 6 weeks, and 8 weeks | 
| Change from Baseline: Change in fecal calprotectin levels | 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. | 2 weeks, 4 weeks, 6 weeks, and 8 weeks | 
| Change from Baseline: Change in plasma inflammatory markers (pg/mL) | Circulating pro-inflammatory cytokine concentrations (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, , and IL-12p70), will be measured simultaneously with a flow cytometry-based multiplex assay. The results will be expressed as change from baseline over time. | 2 weeks, 4 weeks, 6 weeks, and 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn's Disease, Inflammatory Bowel Disease, IBD, Xanthohumol, Humulus lupulus, Hops