Ignite Creation Date:
2024-10-26 @ 3:39 PM
Last Modification Date:
2024-10-26 @ 3:39 PM
Study NCT ID:
NCT06582329
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-07-31
Brief Title:
Effect of Alpha-1 Antitrypsin Supplementation on Alcohol-Associated Hepatitis
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Effect of Alpha-1 Antitrypsin Supplementation on Alcohol-Associated Hepatitis - a Prospective Pilot Study
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
EARTH
Brief 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
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 ie 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 mgdL had a significantly increased risk for deathliver 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
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 mgdL had a significantly increased risk for deathliver 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None