Phase III Placebocontrolled, Randomized Clinical Trial with Synthetic Crohn's Disease Patients to Evaluate Treatment Response

V. Abedi, P. Lu, R. Hontecillas, M. Verma, G. A. Vess, C. W. Philipson, A. Carbo, A. Leber, N. T. Juni, S. Hoops, J. Bassaganya-Riera

Research output: Chapter in Book/Report/Conference proceedingChapter

12 Scopus citations


Crohn's disease (CD) is one of the two most prevailing clinical manifestations of inflammatory bowel disease (IBD), a disease that afflicts 1.4 million Americans and 4 million people worldwide. The current treatment paradigm for IBD includes medications with limited efficacy and significant side effects. Thus, there is an unmet clinical need for safer and more effective CD therapeutics. Drug discovery and development is a lengthy and costly process, especially in clinical trial stages requiring billions of dollars to advance new products to market. To accelerate the path to cures, we have developed a novel integrated approach for creating a synthetic patient population and testing the efficacy of novel therapeutics for CD in large clinical cohorts in silico. By using supervised machine learning methods, thousands of virtual patients were created based on clinical and immunological data of CD patients. A nutritional intervention, conjugated linoleic acid, a Phase IIa therapeutic targeting mothers against decapentaplegic homolog 7 (SMAD7), GED-0301, a novel preclinical stage lanthionine synthetase cyclase-like 2 (LANCL2) therapeutic, and a placebo were administered to 10,000 virtual patients in silico. Efficacy of these treatments on CD was evaluated by analyzing predicted changes of Crohn's Disease Activity Index (CDAI) scores and correlations with immunological variables. Our study shows that targeting LANCL2, a novel therapeutic target for inflammation and diabetes, significantly ameliorates disease activity of CD patients with an average drop of 126 points of CDAI for severe cases. This is the first study to design and implement an in silico Phase III clinical trial for CD to investigate response to treatment in terms of changes in pharmacodynamic immunological marker profiles (ie, TNF-α and IFN-γ) and health outcomes.

Original languageEnglish (US)
Title of host publicationEmerging Trends in Applications and Infrastructures for Computational Biology, Bioinformatics, and Systems Biology
Subtitle of host publicationSystems and Applications
PublisherElsevier Inc.
Number of pages17
ISBN (Electronic)9780128042595
ISBN (Print)9780128042038
StatePublished - Mar 22 2016

All Science Journal Classification (ASJC) codes

  • General Computer Science


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