Effect of ingested interferon-alpha on beta-cell function in children with new-onset type 1 diabetes

Kristina I Rother, Rebecca J Brown, Miriam M Morales, Elizabeth Wright, Zhigang Duan, Carol Campbell, Dana S Hardin, Jadranka Popovic, Robert C McEvoy, David M Harlan, Philip R Orlander, Staley A Brod, Kristina I Rother, Rebecca J Brown, Miriam M Morales, Elizabeth Wright, Zhigang Duan, Carol Campbell, Dana S Hardin, Jadranka Popovic, Robert C McEvoy, David M Harlan, Philip R Orlander, Staley A Brod

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00024518.

Figures

Figure 1
Figure 1
Patient flow diagram. ANA, anti-nuclear antibodies.
Figure 2
Figure 2
Changes over time in 88 subjects with new-onset type 1 diabetes who completed 12 months of treatment with either once-daily placebo (n = 30) or 5,000 units (n = 27) or 30,000 units (n = 31) ingested hrIFN-α. A: Percent change in C-peptide AUC after a mixed-meal test. B: C-peptide AUC after a mixed-meal test. C: A1C. D: Insulin dose.

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