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

  title={A Phase II, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study Evaluating the Efficacy and Safety of Alpha-1 Antitrypsin (AAT) (Glassia{\textregistered}) in the Treatment of Recent-Onset Type 1 Diabetes},
  author={Yael Lebenthal and Avivit Brener and Eli Hershkovitz and Naim Shehadeh and Shlomit Shalitin and Eli C. Lewis and Dana Elias and Alon Haim and Galia Barash and Neta Loewenthal and Nehama Zuckerman-Levin and Michal Stein and Naveh Tov and Marianna Rachmiel},
  journal={International Journal of Molecular Sciences},
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… 
Therapeutic Potential of Alpha-1 Antitrypsin in Type 1 and Type 2 Diabetes Mellitus
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Distinct anti-inflammatory properties of alpha1-antitrypsin and corticosteroids reveal unique underlying mechanisms of action.
AAT may represent a distinct endogenous anti-inflammatory, resolution-promoting agent that may improve tissue well-being while preventing undesired corticostroids side effects.
A mutant α1antitrypsin in complex with heat shock proteins as the primary antigen in type 1 diabetes in silico investigation
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The Role of Proteases and Serpin Protease Inhibitors in β-Cell Biology and Diabetes
Regulation of the equilibrium between proteases and their inhibitors is fundamental to health maintenance. Consequently, developing a means of targeting protease activity to promote tissue
Endogenous α1‐antitrypsin levels in the perilymphatic fluid correlates with severity of hearing loss
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  • Medicine
    Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery
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To determine the levels of endogenous α1‐antitrypsin in the perilymph of patients undergoing cochlear implant (CI), and its reverse association with the severity of hearing loss, data are drawn on patients undergoing CI.
From friend to foe: Pro-apoptotic action of nuclear ARC in diabetes.
Apoptosis repressor with caspase recruitment domain can assume potent pro-apoptotic effects in β cells of the endocrine pancreas via translocation to the nucleus, according to McKimpson et al.


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This prospective, open-label Phase I/II extension study demonstrated that the administration of multiple repeated AAT infusions to AAT-sufficient pediatric T1D patients is safe and well-tolerated.
α1-Antitrypsin therapy downregulates toll-like receptor-induced IL-1β responses in monocytes and myeloid dendritic cells and may improve islet function in recently diagnosed patients with type 1 diabetes.
It is hypothesize that AAT may have a beneficial effect on T1D in recently diagnosed patients that is associated with downmodulation of IL-1β.
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    Annals of internal medicine
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As in the entire DCCT cohort, intensively treated responders had a reduced risk for retinopathy progression and development of microalbuminuria and a higher risk for severe hypoglycemia compared with conventionally treated responders.
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    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
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Findings show that AAT is well tolerated and has efficacy in the treatment of steroid-refractory severe acute GVHD, and further studies are warranted.
Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus.
Treatment with hOKT3gamma1(Ala-Ala) mitigates the deterioration in insulin production and improves metabolic control during the first year of type 1 diabetes mellitus in the majority of patients.
Exploration of α1-Antitrypsin Treatment Protocol for Islet Transplantation: Dosing Plan and Route of Administration
Results indicate that dividing the commonly prescribed 60mg/kg i.p. dose to three 20 mg/kg injections is superior in affording islet graft survival; in addition, a short dynamic descending dose protocol is comparable in outcomes to indefinite 60 mg/ kg injections.
Fall in C-Peptide During First 2 Years From Diagnosis
The natural history of β-cell function from shortly after diagnosis through 2 years post study randomization is described, the degree of variability between patients is assessed, and factors that may be related to C-peptide preservation or loss are investigated.
Intradermal α1-antitrypsin therapy avoids fatal anaphylaxis, prevents type 1 diabetes and reverses hyperglycaemia in the NOD mouse model of the disease
Intradermal hAAT prevents and reverses disease in a NOD mouse model of type 1 diabetes without inducing anaphylaxis and allows evaluation of hA AT’s potential for diabetes prevention and reversal.
Effect of Intensive Therapy on Residual -Cell Function in Patients with Type 1 Diabetes in the Diabetes Control and Complications Trial
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At clinical onset of type 1 diabetes mellitus, most patients retain some insulin secretory capacity, as exemplified by the so-called honeymoon phase of the disease. During this period, patients often
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Even in a restricted geographical area and narrow age range (<18 years), the natural course of Type 1 diabetes is heterogeneous, and this should be considered in clinical trials.