Effect of Ingested Interferon-α on β-Cell Function in Children With New-Onset Type 1 Diabetes
- Kristina I. Rother, MD, MHSC1,
- Rebecca J. Brown, MD1,
- Miriam M. Morales, BS2,
- Elizabeth Wright, PHD, MPH1,
- Zhigang Duan, MS1,
- Carol Campbell, CRNP1,
- Dana S. Hardin, MD3,
- Jadranka Popovic, MD4,
- Robert C. McEvoy, MD5,
- David M. Harlan, MD1,
- Philip R. Orlander, MD6 and
- Staley A. Brod, MD2
- 1National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland;
- 2University of Texas Medical School, Department of Neurology, Houston, Texas;
- 3University of Texas Southwestern, Dallas, Texas;
- 4Children's Mercy Hospital & Clinics, Kansas City, Missouri;
- 5St. Paul Children's Hospital, St. Paul, Minnesota;
- 6University of Texas Medical School, Department of Internal Medicine, Houston, Texas.
- Corresponding author: Kristina I. Rother, .
OBJECTIVE To evaluate the safety and efficacy of ingested human recombinant interferon-α (hrIFN-α) for preservation of β-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-α 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-α 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-α was safe at the doses used. Patients in the 5,000-unit hrIFN-α treatment group maintained more β-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-α. Further studies of low-dose ingested hrIFN-α in new-onset type 1 diabetes are needed to confirm this effect.
A full list of investigators can be found in an online appendix.
Clinical trial reg. no. NCT00024518, clinicaltrials.gov.
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- Received November 11, 2008.
- Accepted March 25, 2009.
- © 2009 by the American Diabetes Association.
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