ArticlePediatric diabetes2018
Alpha-1 antitrypsin treatment of new-onset type 1 diabetes: An open-label, phase I clinical trial (RETAIN) to assess safety and pharmacokinetics.
Article in Pediatric diabetes, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05973734 (Clinical Islet Transplantation With Apheresis, Isolation and Reintroduction of Recipient Regulatory T Cells or Administration of Deceased Donor Vertebral Bone Marrow in Type 1 Diabetes), which is not on this map. Cited by 15 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Clinical Islet Transplantation With Apheresis, Isolation and Reintroduction of Recipient Regulatory T Cells or Administration of Deceased Donor Vertebral Bone Marrow in Type 1 Diabetes
Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Human plasma-derived alphaPediatric diabetes · 2021Trial
- A Phase II, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study Evaluating the Efficacy and Safety of Alpha-1 Antitrypsin (AAT) (GlassiaInternational journal of molecular sciences · 2019Trial
- Alpha-1 Antitrypsin Augmentation Therapy in Chronic Pancreatitis Patients Undergoing Total Pancreatectomy and Islet Autotransplantation: A Randomized, Controlled Study.Cell transplantationTrial
- Mechanisms Linking COPD to Type 1 and 2 Diabetes Mellitus: Is There a Relationship between Diabetes and COPD?Medicina (Kaunas, Lithuania) · 2022Review
- Role of IKKε in the Metabolic Diseases: Physiology, Pathophysiology, and Pharmacology.Frontiers in pharmacology · 2022Review
- Therapeutic Potential of Alpha-1 Antitrypsin in Type 1 and Type 2 Diabetes Mellitus.Medicina (Kaunas, Lithuania) · 2021Review
- Continuous-Flow Synthesis of ZIF-8 Biocomposites with Tunable Particle Size.Angewandte Chemie (International ed. in English) · 2020Article
- New Frontiers in the Treatment of Type 1 Diabetes.Cell metabolism · 2020Review
- Prediction and Prevention of Type 1 Diabetes.Frontiers in endocrinology · 2020Review
- Alpha-1 Antitrypsin Deficiency and Accelerated Aging: A New Model for an Old Disease?Drugs & aging · 2019Review
- Improving engraftment of hepatocyte transplantation using alpha-1 antitrypsin as an immune modulator.Journal of molecular medicine (Berlin, Germany) · 2019Article
- Alpha-1 Antitrypsin Therapy for Autoimmune Disorders.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2018Article
- Alpha-1 Antitrypsin Substitution for Extrapulmonary Conditions in Alpha-1 Antitrypsin Deficient Patients.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2018Article
- Immune Mechanisms and Pathways Targeted in Type 1 Diabetes.Current diabetes reports · 2018Review
- Changes in Serum Proteomic Profiles at Different Stages of Pregnancy Toxemia in Goats.Journal of veterinary internal medicineArticle
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
objectiveTo determine the safety and pharmacokinetics of alpha-1 antitrypsin (AAT) in adults and children. RESEARCH DESIGN AND
methodsShort-term AAT treatment restores euglycemia in the non-obese mouse model of type 1 diabetes. A phase I multicenter study in 16 subjects with new-onset type 1 diabetes studied the safety and pharmacokinetics of Aralast NP (AAT). This open-label, dose-escalation study enrolled 8 adults aged 16 to 35 years and 8 children aged 8 to 15 years within 100 days of diagnosis, to receive 12 infusions of AAT: a low dose of 45 mg/kg weekly for 6 weeks, followed by a higher dose of 90 mg/kg for 6 weeks.
resultsC-peptide secretion during a mixed meal, hemoglobin A1c (HbA1c), and insulin usage remained relatively stable during the treatment period. At 72 hours after infusion of 90 mg/kg, mean levels of AAT fell below 2.0 g/L for 7 of 15 subjects. To identify a plasma level of AAT likely to be therapeutic, pharmacodynamic ex vivo assays were performed on fresh whole blood from adult subjects. Polymerase chain reaction (PCR) analyses were performed on inhibitor of IKBKE, NOD1, TLR1, and TRAD gene expression, which are important for activation of nuclear factor-κB (NF-κB) and apoptosis pathways. AAT suppressed expression dose-dependently; 50% inhibition was achieved in the 2.5 to 5.0 mg/mL range.
conclusionsAAT was well tolerated and safe in subjects with new-onset type 1 diabetes. Weekly doses of AAT greater than 90 mg/kg may be necessary for an optimal therapeutic effect.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.