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

NCT04590508 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: Placeholder
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Crohn Disease

Keywords

Crohn's Disease; Inflammatory Bowel Disease; IBD; Xanthohumol; Humulus lupulus; Hops

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (3)

• Change from Baseline: Composite Symptoms: Crohn's Disease Activity Index (CDAI)

  2 weeks, 4 weeks, 6 weeks, and 8 weeks

• Change from Baseline: Change in fecal calprotectin levels

  2 weeks, 4 weeks, 6 weeks, and 8 weeks

• Change from Baseline: Change in plasma inflammatory markers (pg/mL)

  2 weeks, 4 weeks, 6 weeks, and 8 weeks

Study Arms (2)

Xanthohumol

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Participants will receive capsules filled with a rice protein vehicle by mouth once daily with the first daily meal.

Other: Placebo

Interventions

Xanthohumol DRUG

The xanthohumol supplement will be administered in a capsule and taken orally.

Xanthohumol

Placebo OTHER

The placebo will be administered in a capsule and taken orally.

Placebo

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• National University of Natural Medicine: lead
• Oregon State University: collaborator
• Pacific Northwest National Laboratory: collaborator

Study Sites (1)

National University of Natural Medicine

Portland, Oregon, 97201, United States

Location

Related Publications (1)

• 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.

  PMID: 36273173 DERIVED

MeSH Terms

Conditions

Crohn Disease; Inflammatory Bowel Diseases

Interventions

xanthohumol

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Officials

• Ryan Bradley, ND/MPH

  National University of Natural Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Randomization will occur in up to 8 blocks of 4 based on biological sex. Initial randomization series will be generated using readily available random sequence generators designed to do so. A series of sequential envelopes will be generated, each containing the allocation for one participant. Envelopes will be opaque and signed across the seal. The randomization "code" will be kept in a sealed envelope with a signature across the label and dated the day of creation. Study product and comparator (placebo) will be compounded and placed in identical opaque capsules outside the institution.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomized to receive either encapsulated xanthohumol in a rice protein vehicle, or an identical capsule containing vehicle alone.

Study Record Dates

• First Submitted: September 28, 2020
• First Posted: October 19, 2020
• Study Start: October 1, 2020
• Primary Completion: August 22, 2024
• Study Completion: July 30, 2025
• Last Updated: October 18, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: We will share our data no later than on acceptance of the first publication of the findings from the respective data set(s).

Locations

US (1)