Scientific Abstract
Proposal No. IBD-0285
Principal Investigator: David Ziring, M.D.
Applicant Organization: University of California, Los Angeles (U.S.A.)
Project Title: Vitamin D supplementation as non-toxic immunomodulation in children with Crohn’s disease
Period of Award: January 1, 2010 – December 31, 2012
Our aims for this pilot study are to enroll 20 children ages 8 to 18 years with mild to moderate Crohn’s disease in a study of vitamin D supplementation as non-toxic immunomodulation. Primary endpoints will be analysis of serum levels of the main circulating form of vitamin D , 25-OH vitamin D, as well as changes in patient monocyte cathelicidin mRNA expression and serum cathelicidin protein levels. Secondary endpoints will include changes in disease activity scores, inflammatory markers, and serum cytokine concentration.
We anticipate that patients supplemented with vitamin D will achieve a target serum 25-OH vitamin D level between 40 and 70 ng/mL. In association with supplementation, we would also expect to see an increase in cathelicidin mRNA in monocytes from peripheral blood as well as serum cathelicidin levels. As a pilot project, this study will not be powered to detect small changes in clinical disease activity, but rather is designed to determine the optimal dosing in children, prove that this is a safe intervention, and detect a significant biological signal of immune modulation.
Period of Award: January 1, 2010 – December 31, 2012
Vitamin D deficiency is prevalent among patients with Crohn’s disease. While much research has been done on the link between vitamin D deficiency and skeletal health in patients with Crohn’s disease, very little attention has been paid to the role of vitamin D deficiency in the immunology of Crohn’s disease. Both Crohn’s disease and vitamin D deficiency share similar perturbations in both the innate and acquired immune systems. Direct effects of vitamin D, mediated via the intracellular vitamin D receptor, include induction of the anti-microbial peptide cathelicidin in monocytes. Vitamin D supplementation in normal human subjects increases their levels of cathelicidin production, whilst patients with colonic Crohn’s disease have impaired production of cathelicidin. Based on these observations we have hypothesized that vitamin D deficiency is a correctable environmental contributor to Crohn’s disease susceptibility.
Our aims for this pilot study are to enroll 20 children ages 8 to 18 years with mild to moderate Crohn’s disease in a study of vitamin D supplementation as non-toxic immunomodulation. Primary endpoints will be analysis of serum levels of the main circulating form of vitamin D , 25-OH vitamin D, as well as changes in patient monocyte cathelicidin mRNA expression and serum cathelicidin protein levels. Secondary endpoints will include changes in disease activity scores, inflammatory markers, and serum cytokine concentration.
We anticipate that patients supplemented with vitamin D will achieve a target serum 25-OH vitamin D level between 40 and 70 ng/mL. In association with supplementation, we would also expect to see an increase in cathelicidin mRNA in monocytes from peripheral blood as well as serum cathelicidin levels. As a pilot project, this study will not be powered to detect small changes in clinical disease activity, but rather is designed to determine the optimal dosing in children, prove that this is a safe intervention, and detect a significant biological signal of immune modulation.