Alpha-1 Antitrypsin (AAT), trade name (Glassia ®), is being explored in this phase I/II trial as a potential disease modifying agent in Type 1 Diabetes Mellitus (T1DM) based on its anti-inflammatory properties. AAT is an acute stress reactant protein that increases during inflammation. In T1DM inflammation serves a major role in disease progression.
AAT is a protein produced by the human liver and secreted into the blood circulation. AAT, which belongs to a group of serine protease inhibitors (SERPINS) is an acute stress reactant protein that increases during stress conditions, including inflammation. AAT blocks serine proteases that enhance pro-inflammatory mediators (i.e. IL-1 alpha, IL-6, IL-8, TNFalpha) as well as induces production of anti-inflammatory mediators (i.e. IL-10 and IL-1-receptor antagonist). In Type 1 Diabetes Mellitus (T1DM) inflammation serves a major role in disease progression. The inflammatory signature pattern in these patients appears to have been present years before clinical onset. Although circulating levels of AAT in T1DM are normal, in majority of cases, the activity of AAT is severely compromised by non-enzymatic glycations, supporting the conclusion that serum protease inhibitory capacity is reduced in T1DM. It has been shown in different studies, including in vivo and in vitro that AAT has a protective affect on pancreatic islets. This has been demonstrated in both decrease in progression of diabetes in the non-obese diabetic (NOD) mouse as well as during transplantation of islets which presented viability and activity (insulin production) in the presence of AAT. More specifically, islet cells are protected by human AAT from apoptosis, as shown by reduced caspase-3 activity after the addition of human AAT to islet culture media. Based on the mentioned anti-inflammatory properties of AAT sided to in vivo and in vitro studied indicating that AAT may serve as a disease modifying agent in T1DM, the presented study is suggested.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Each study group will undergo 3 treatment periods:12 weeks, 8 weeks and 4 weeks.
Each study group will undergo 3 treatment periods:12 weeks, 8 weeks and 4 weeks.
Each study group will undergo 3 treatment periods:12 weeks, 8 weeks and 4 weeks.
Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes at Schneider Children's Medical Center of Israel
Petah Tikva, Israel, Israel
Assaf Haroffeh Medical Center
Ẕerifin, Israel, Israel
Safety and Tolerability
Safety and Tolerability: assessed by vital signs(systolic/diastolic blood pressure and heart rate), physical examination, routine safety lab tests, AEs and SAEs.
Time frame: Approximately 1 year
Efficacy
Pancreatic beta cell function ; External Insulin dose requirements; Glycosylated hemoglobin (HbA1c) levels.
Time frame: Approximately 1 year
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.