NCT01304537

Study of the Safety and Efficacy of Intravenous Alpha-1 Antitrypsin in Type 1 Diabetes Mellitus

Open Label, Proof of Concept, Phase I/II Study of the Safety, Tolerability and Efficacy of Intravenous Alpha-1 Antitrypsin (AAT) [Trade Name Glassia™] in Type 1 Diabetes Mellitus

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 24 (actual)
• Sponsor: Kamada, Ltd. · Industry
• Sex: All
• Age: 10 Years – 25 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Type 1 Diabetes Mellitus

Interventions

Type	Name	Description
DRUG	Alpha-1 Antitrypsin 40mg (AAT, Glassia®)	Each study group will undergo 3 treatment periods:12 weeks, 8 weeks and 4 weeks.
DRUG	Alpha-1 Antitrypsin 60mg (AAT, Glassia®)	Each study group will undergo 3 treatment periods:12 weeks, 8 weeks and 4 weeks.
DRUG	Alpha-1 Antitrypsin 80mg (AAT, Glassia®)	Each study group will undergo 3 treatment periods:12 weeks, 8 weeks and 4 weeks.

Timeline

• Start date: 2011-06-01
• Primary completion: 2012-11-01
• Completion: 2012-11-01
• First posted: 2011-02-25
• Last updated: 2016-06-09

Locations

2 sites across 1 country: Israel