Project Summary The parent study, Xanthohumol Microbiome and Signature (XMaS), is a RO1-funded, multiple principal investigator-led, FDA-approved clinical trial that completed its Phase 1 clinical operation earlier this year. The Phase 1 trial aimed to determine the safety and tolerability of a natural product made from xanthohumol (XN), a compound found in Humulus lupulus (hops), in healthy adults. In addition to assessing safety, collaborators on the trial from Oregon State University will also generate data on XN metabolites and its effects on biomarkers of inflammation and gut integrity, and collaborators at the Pacific Northwest National Laboratory will determine the effects of XN on the microbiota through sequencing and metabolomics profiling. Collectively, these data will be used as comparison data for the Phase 2 clinical trial in Crohn’s Disease, which began recruitment on September 16th, 2020. The additional support of a second-year administrative supplement for Dr. Langley will allow for continued training opportunity for a post-doctoral, early-career Complementary and Integrative Health (CIH) clinician by: 1. Building upon experience in the conduct of clinical trials through participation in the operational aspects of an active clinical trial while under the leadership and mentorship of an experienced team of researchers; 2. Gaining exposure and instruction on the translational scientific methods and techniques used in the collaborative laboratories of the multi-PI team; 3. Encouraging skill development in technical writing, presentation, publication, and statistical analysis; and 4. Developing skills in biostatistics, epidemiology, and clinical trial methodology through didactic coursework. Trial participation will be initiated by training the candidate in clinical screenings and other visits, including: collection of survey data and biologic specimens, and adverse event reporting, as outlined in the trial protocol. The candidate will also gain exposure to specific assays included in the trial, such as microbiota sequencing and metabolomic profiling, through hands-on experience with rotations in each collaborative lab. Finally, skills development in biostatistics, presentation, and future publication will be conducted by finalizing the scoping review currently in development, biostatistics and epidemiology coursework, continuing manuscript development, and performing secondary data analysis under the mentorship of our resident biostatistician. With the successful completion of his initial year of training, a second year of support for Dr. Langley will provide valuable experience as he becomes more competitive for future training awards in clinical and translational research.

Project Narrative Over the past several decades there has been an increased public use of complementary and integrative health (CIH) therapies, and a corresponding decrease in the number of clinicians pursuing clinical research careers, with very few pursuing clinical CIH research. One recognized barrier to entry into clinical research careers is the availability of mentorship and training in clinical research. This proposal leverages an active NIH-funded Phase 2 clinical trial of a natural product in participants with Crohn’s disease to provide a mentorship and training opportunity to a CIH practitioner in order to provide continued experiences in the conduct of clinical research, allow for rotations through translational science laboratories and begin developing skills through research presentations and publications.