Rother KI, Brown RJ, Morales MM, Wright E, Duan Z, Campbell C, Harlan DM, Orlander PR, Brod SA, Hardin DS, Popovic J, McEvoy RC, Rother, Kristina I, Brown, Rebecca J, Morales, Miriam M, Wright, Elizabeth, Duan, Zhigang, Campbell, Carol, Hardin, Dana S, and Popovic, Jadranka
Objective: To evaluate the safety and efficacy of ingested human recombinant interferon-alpha (hrIFN-alpha) for preservation of beta-cell function in young patients with recent-onset type 1 diabetes.Research Design and Methods: Subjects aged 3-25 years in whom type 1 diabetes was diagnosed within 6 weeks of enrollment were randomly assigned to receive ingested hrIFN-alpha at 5,000 or 30,000 units or placebo once daily for 1 year. The primary outcome was change in C-peptide secretion after a mixed meal.Results: Individuals in the placebo group (n = 30) lost 56 +/- 29% of their C-peptide secretion from 0 to 12 months, expressed as area under the curve (AUC) in response to a mixed meal. In contrast, children treated with hrIFN-alpha lost 29 +/- 54 and 48 +/- 35% (for 5,000 [n = 27] and 30,000 units [n = 31], respectively, P = 0.028, ANOVA adjusted for age, baseline C-peptide AUC, and study site). Bonferroni post hoc analyses for placebo versus 5,000 units and placebo versus 30,000 units demonstrated that the overall trend was determined by the 5,000-unit treatment group. Adverse events occurred at similar rates in all treatment groups.Conclusions: Ingested hrIFN-alpha was safe at the doses used. Patients in the 5,000-unit hrIFN-alpha treatment group maintained more beta-cell function 1 year after study enrollment than individuals in the placebo group, whereas this effect was not observed in patients who received 30,000 units hrIFN-alpha. Further studies of low-dose ingested hrIFN-alpha in new-onset type 1 diabetes are needed to confirm this effect. [ABSTRACT FROM AUTHOR]