Alpha-1 antitrypsin therapy is safe and well tolerated in children and adolescents with recent onset type 1 diabetes mellitus
Background and objectives Alpha‐1 antitrypsin (AAT) has been shown to reduce pro‐inflammatory markers and protect pancreatic islets from autoimmune responses in recent studies. Our aim was to evaluate its safety and tolerability in three different doses, in a pediatric population with recent onset t...
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Published in | Pediatric diabetes Vol. 17; no. 5; pp. 351 - 359 |
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Main Authors | , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Former Munksgaard
John Wiley & Sons A/S
01.08.2016
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Subjects | |
Online Access | Get full text |
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Summary: | Background and objectives
Alpha‐1 antitrypsin (AAT) has been shown to reduce pro‐inflammatory markers and protect pancreatic islets from autoimmune responses in recent studies. Our aim was to evaluate its safety and tolerability in three different doses, in a pediatric population with recent onset type 1 diabetes mellitus (T1DM).
Methods
A 37‐wk prospective, open‐label, phase I/II interventional trial, comprised of 24 recently diagnosed subjects (12 males; age 12.9 ± 2.4 yr), who received 18 infusions of 40, 60, or 80 mg/kg/dose high‐purity, liquid, ready to use AAT over 28 wk (Glassia®; Kamada Ltd., Ness Ziona, Israel). Primary outcomes: safety and tolerability; secondary outcomes: glycemic control, C‐peptide reserve, and autoantibody levels. Possible responders were defined as individuals with peak C‐peptide that declined less than 7.5% below baseline.
Results
No serious adverse events, diabetic ketoacidosis (DKA), or severe hypoglycemic episodes were reported. Adverse events were dose‐independent and transient. Glycemic control parameters improved during the study in all groups, independent of dosage. Hemoglobin A1c (HbA1c) decreased from 8.43 to 7.09% (mean, p < 0.001). At the end of the study, 18 subjects (75%) had a peak C‐peptide ≥0.2 pmol/mL. Eight subjects (33.3%) were considered possible responders and were characterized by shorter duration of T1DM at screening (54.5 ± 34.3 vs. 95.9 ± 45.7 d, p = 0.036) and greater decrease in their HbA1c during the study period (−2.94 ± 1.55 vs.−0.95 ± 1.83%, p = 0.016).
Conclusions
AAT treatment was safe and well tolerated in pediatric subjects with recently diagnosed autoimmune diabetes. Placebo‐controlled studies with larger cohorts and dose range are warranted in order to assess efficacy in maintaining pancreatic beta cell reserve and glycemic control. |
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Bibliography: | Parts of this study were presented in abstract form at the 6th International Conference on Advanced Technologies and Treatment for Diabetes (ATTD), Paris, France February, 2013. Kamada Ltd istex:4A84A5520DD83CF1A897BE7687F6680E2EA888DF ArticleID:PEDI12283 ark:/67375/WNG-DKN75XFX-L ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Undefined-1 ObjectType-Feature-3 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 1399-543X 1399-5448 |
DOI: | 10.1111/pedi.12283 |