Clinical trial NCT02837939: Transfer Factor Efficacy in the Management of Cirrhosis-associated Immune Dysfunction
Official title: Prospective Randomized Single-blind Study on Transfer-factor in Acute Decompensation of Advanced Chronic Liver Disease and Acute-on-chronic Liver Failure.
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
PHASE3
Conditions: Cirrhosis
Liver Failure
Lead sponsor: Pavol Jozef Safarik University
Sponsor class: OTHER
Collaborators: name: F.D. Roosevelt Teaching Hospital with Policlinic Banska Bystrica
First posted: 2016-07-20
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This 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..

Detailed description: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Composite endpoint that includes the incidence specified infections:
timeFrame: Two years
Secondary outcomes:
measure: Length of hospital stay
timeFrame: Two years
measure: The usage of antibiotics required for treatment of a diagnosed infection
timeFrame: Two years
measure: The incidence of adverse effects
timeFrame: 2 years
Other outcomes:
measure: Change in the phagocytic activity of macrophages
timeFrame: 6 months
measure: Changes in the levels of imunoglobulins IgA, IgG, IgM, IgD, IgE
timeFrame: 6 months
measure: Changes in the capacity for oxidative burst in macrophages
timeFrame: 6 months
measure: Changes in the complement levels and activation pathways activity
timeFrame: 6 months
measure: Changes in lymphocyte subpopulations
timeFrame: 6 months
measure: Changes in the levels of immunomodulators - IL-6, TNF alpha
timeFrame: 6 months
Locations:
city: Banska Bystrica
country: Slovakia
facility: F.D.Roosevelt Teaching Hospital with policlinic Banska Bystrica
Study officials:
affiliation: F.D.Roosevelt Teaching Hospital with policlinic, Banska Bystrica, Slovakia, 97517
name: Lubomir Skladany, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: