Transfer Factor Efficacy in the Management of Cirrhosis-associated Immune Dysfunction

NCT ID: NCT02837939

Last Updated: 2023-11-18

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2/PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-07-31
• Study Completion Date: 2025-07-31

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.

Conditions

Cirrhosis; Liver Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Active

Drug: Human derived Transfer factor applied by subcutaneous injection in specified time points.

Group Type: EXPERIMENTAL

Human derived Transfer factor

Intervention Type: DRUG

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

Control

Aqua pro injectione 4 mL ampules for subcutaneous administration in the same time points as in the active arm

Group Type: PLACEBO_COMPARATOR

Aqua pro injectione 4ml ampules for subcutaneous injection

Intervention Type: DRUG

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

Interventions

Human derived Transfer factor

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

Intervention Type: DRUG

Aqua pro injectione 4ml ampules for subcutaneous injection

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

Intervention Type: DRUG

Other Intervention Names

IMMODIN. Holder: IMUNA PHARM a.s. - GRIFOLS (SVK) Registration number: 59/0147/89-CS

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

F.D. Roosevelt Teaching Hospital with Policlinic Banska Bystrica

OTHER

Sponsor Role: collaborator

Martin Janičko

OTHER

Sponsor Role: lead

Responsible Party

Martin Janičko

Assistant Professor of Medicine, Faculty of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Lubomir Skladany, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

F.D.Roosevelt Teaching Hospital with policlinic, Banska Bystrica, Slovakia, 97517

Locations

F.D.Roosevelt Teaching Hospital with policlinic Banska Bystrica

Banská Bystrica, , Slovakia

Countries

Slovakia

Other Identifiers

IMUNO - HEGITO 7

Identifier Type: -

Identifier Source: org_study_id