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Open AccessArticle

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

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The Jesse Z. and Sara Lea Shafer Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider Children’s Medical Center, Petah-Tikva affiliated with Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
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Pediatric Diabetes Unit, Soroka Medical Center, Beer-Sheva affiliated with Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel
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Pediatric Diabetes Unit, Meyer Children’s Hospital, Rambam Medical Center, Haifa affiliated with Bruce Rappaport Faculty of Medicine, Technion, Haifa 319601, Israel
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Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva 8410501, Israel
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Kamada Ltd., 2 Holzman St., Science Park, Rehovot 7670402, Israel
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Pediatric Endocrinology Unit, Assaf Harofeh Medical Center, Zerifin, Israel affiliated with Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(23), 6032; https://doi.org/10.3390/ijms20236032
Received: 3 November 2019 / Revised: 25 November 2019 / Accepted: 27 November 2019 / Published: 29 November 2019
(This article belongs to the Special Issue Advances in Immunotherapeutic Approaches to Type 1 Diabetes)
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, C-peptide 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. View Full-Text
Keywords: alpha-1 antitrypsin; type 1 diabetes; children and adolescents; beta cell preservation alpha-1 antitrypsin; type 1 diabetes; children and adolescents; beta cell preservation
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Lebenthal, Y.; Brener, A.; Hershkovitz, E.; Shehadeh, N.; Shalitin, S.; Lewis, E.C.; Elias, D.; Haim, A.; Barash, G.; Loewenthal, N.; Zuckerman-Levin, N.; Stein, M.; Tov, N.; Rachmiel, M. 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. Int. J. Mol. Sci. 2019, 20, 6032.

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