Title
Transfer Factor Efficacy in the Management of Cirrhosis-associated Immune Dysfunction
Prospective Randomized Single-blind Study on Transfer-factor in Acute Decompensation of Advanced Chronic Liver Disease and Acute-on-chronic Liver Failure.
Phase
Phase 2/Phase 3Lead Sponsor
Pavol Jozef Safarik UniversityStudy Type
InterventionalStatus
WithdrawnIndication/Condition
Cirrhosis Liver FailureIntervention/Treatment
human transfer factor ...Study Participants
0This study is aimed to assess the efficacy of Human derived Transfer factor ( T-lymphocytes homogenate that contains small molecular weight (10 kDa) molecules: various IFNs, ILs, chemokines, endorfins, heat shock proteins) in decreasing rate and/or severity of infections in acute or chronic decompensations of liver cirrhosis and acute on chronic liver failure..
Most of mortality from advanced chronic liver disease (ACLD) is mediated by so- called specific complications of end-stage liver disease (ESLD); one of the most important is infection (25-30%). Infection is responsible for considerable proportion of ESLD-related mortality. Important in pathogenesis of infections in ESLD is CAIDS (cirrhosis - associated immune dysfunction syndrome), recently re-named to CAID (Cirrhosis-Associated Immune Deficit). TRANSFER FACTOR (TF) is supposed to act at several points in CAID - cascade. This gave rise to hypothesis, that TF could be of benefit in AD/ACLF.
Characteristics of TF It has been shown that transmission fo T-Lymphocyte reactivity is transmissible not only by T-cells alone, but also by hommogenate of peripheral white blood cells. Later it became clear that for the transmission of cellular immunity is responsible dialysable fraction of T-lymphocytes homogenate (with small molecular weight of 10 kDa; consists of amino acids, small peptides, nucleotides etc). This homogenate was named Transfer - factor (TF). One dose of lyophilized drug contains: Leucocyti dialysatum 200 x 10 6 (contains various IFNs, ILs, chemokines, endorfins, heat shock protein etc)
stimulates T H 1 response
induces production of IL-1, IL-2
activates chemotaxis of immunocompetent cells
increases fagocytic activity
activates antigen-presentation by APCs
The aim of this study is to assess the efficacy of transfer factor in decreasing rate and/or severity of infections in ACLF.
One dose (the content of one amp.) of lyophilised drug contains: Leucocyte dialysatum 200 x 10 to the power of 6 (Lyophilized dialysate from 200 million leukocytes) pH = 7.8 to 9 after reconstitution (dissolving) of drug To be administered subcutaneously as follows: 12 doses TF in total: 3 x TF in first week: day 1,3,5 2 x TF in week 2: day 8 , 11 1 xTF in week 3 and 4 : day 15, 22 1 x TF once a month up to 6 month
12 doses in total: 3 doses in first week: day 1,3,5 2 doses in week 2: day 8 , 11 1 dose in week 3 and 4 : day 15, 22 1 dose once a month up to 6 month
Drug: Human derived Transfer factor applied by subcutaneous injection in specified time points.
Aqua pro injectione 4 mL ampules for subcutaneous administration in the same time points as in the active arm
Inclusion Criteria: admission to hospital at participating liver units or ICUs or internal medicine wards with acute decompensation (AD) of advanced chronic liver disease or acute-on-chronic liver failure according to CLIF - C criteria ability to provide informed consent, Exclusion Criteria: disapproval lymphoproliferative disorders liver transplantation in the past pregnancy suspected. chronic infection in risk locations CNS peritoneum Known virus-related immune deficiency malignancy severe heart failure (NYHA >= III) severe lung disease (COPD, GOLD>3)
