A phase II, double-blind, randomized, placebo-controlled, multicenter study evaluating the efficacy and safety of alpha-1 antitrypsin (AAT) (glassia®) in the treatment of recent-onset type 1 diabetes

Yael Lebenthal, Avivit Brener, Eli Hershkovitz, Naim Shehadeh, Shlomit Shalitin, Eli C. Lewis, Dana Elias, Alon Haim, Galia Barash, Neta Loewenthal, Nehama Zuckerman-Levin, Michal Stein, Naveh Tov, Marianna Rachmiel

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11 Scopus citations

Abstract

Our aim was to assess the efficacy, safety, and tolerability of alpha-1 antitrypsin (AAT) as a therapeutic modality for β-cell preservation in patients with recent-onset type 1 diabetes. Seventy type 1 diabetes patients (37 males; mean age 13.1 ± 4.1years) were randomized to treatment with 22 infusions of AAT (Glassia®) (60 or 120 mg/kg) or placebo. The primary outcome was the area under the curve (AUC) of C-peptide from a 2-h mixed-meal tolerance test after 52 weeks. At week 52, Cpeptide was 0.9, 0.45, and 0.48 pmol/mL in the AAT-120, AAT-60, and placebo groups (p = 0.170 and p = 0.866 vs. placebo, respectively). The declines in C-peptide glycated hemoglobin (HbA1c) and the total insulin dose (U/kg) were similar across groups. Within the predefined 12–18-years subgroup, the C-peptide AUC decreased significantly in the placebo and AAT-60 groups (−0.34 and −0.54 pmol/mL, respectively, p < 0.01), with a borderline decrease in the AAT-120 group (−0.29 pmol/mL, p = 0.047). The mean HbA1c level was significantly lower in the AAT-120 group compared to the placebo (6.7% ± 0.9% vs. 8.2 ± 1.4%, p = 0.05), and a higher percentage of patients attained HbA1c ≤ 7% (75% vs. 25%, p = 0.05). AAT was tolerated well, with a similar safety profile between groups. The AAT intervention showed promise in the subgroup of adolescents with recent-onset type 1 diabetes. Further studies are warranted to determine the impact and proposed mechanism of action of AAT in β-cell preservation.

Original languageEnglish
Article number6032
JournalInternational Journal of Molecular Sciences
Volume20
Issue number23
DOIs
StatePublished - 1 Dec 2019

Keywords

  • Alpha-1 antitrypsin
  • Beta cell preservation
  • Children and adolescents
  • Type 1 diabetes

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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