NCT06582329

Effect of Alpha-1 Antitrypsin Supplementation on Alcohol-Associated Hepatitis

Effect of Alpha-1 Antitrypsin Supplementation on Alcohol-Associated Hepatitis - A Prospective Pilot Study

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 16 (estimated)
• Sponsor: Medical University Innsbruck · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The trial is designed as a prospective, single center, open label, randomized controlled pilot study evaluating the effect of A1AT (Alpha 1 Antitrypsin) on inflammation in patients with severe AAH (alcohol-associated hepatitis). The objective is to evaluate the safety and the effect of intravenous A1AT on the systemic inflammation in patients with severe AAH. The objectives also include the assessment of A1AT on clinical outcomes including the incidence of adverse events (AEs) and serious adverse events (SAEs) and the cytokine.

Detailed description

About 5-7 % of patients with alcohol-associated chronic liver disease transform into acute on chronic liver disease (ACLF) per year. In patients with underlying alcohol-associated liver disease (ALD) and active drinking, a sudden onset of jaundice, malaise, decompensated liver disease and coagulopathy i.e. alcohol-associated hepatitis (AAH) might develop. In its severe form, AAH is associated with development of ACLF and bacterial infections and this disease exhibits a high short-term mortality of 20 to 50% within 3 months. Treatment options are limited currently, for instance, the use of corticosteroids. Alpha-1 Antitrypsin (A1AT) acts as an anti-inflammatory protein by inhibiting the generation of pro-inflammatory cytokines. The investigators recently showed protective effects of A1AT in a pre-clinical experimental model of ALD, resulting in decreased levels of pro-inflammatory cytokines, less steatosis and hepatic injury. The investigators also have recently found that cirrhotic patients with A1AT concentrations less than 120 mg/dL had a significantly increased risk for death/liver transplantation in a cohort of 130 patients with ALD cirrhosis. This finding was not only significant, but also independent of the MELD-Na score, indicating that in ALD A1AT is not only a marker of reduced hepatic synthetic function. Further, significantly higher ferritin and lower transferrin in the cohort of patients with low A1AT also indicate more severe inflammation. An interventional analysis in an established mouse model of ALD showed that A1AT supplementation mitigated inflammation and histological changes further indicating that low AAT (Alpha 1 Antitrypsin) is a driver and not the consequence of tissue damage in ALD. These data support the use of A1AT in humans with severe AAH. As a pilot trial the study also aims to establish important preliminary data for future studies and design of larger trials aimed at formal evaluation of the effect of A1AT on clinical endpoints.

Conditions

• Alcohol-Associated Hepatitis

Interventions

Type	Name	Description
DRUG	Alfa1 Antitrypsin	Participants will be treated intravenously with A1AT 120 mg/kg bodyweight once a week for 4 weeks (4 total infusions).

Timeline

• Start date: 2025-04-01
• Primary completion: 2025-07-01
• Completion: 2026-12-01
• First posted: 2024-09-03
• Last updated: 2025-03-06

Locations

1 site across 1 country: Austria