Improved Prevention of Perinatal Hepatitis B Transmission

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2010 by Hadassah Medical Organization.
Recruitment status was  Not yet recruiting
Sponsor:
Information provided by:
Hadassah Medical Organization
ClinicalTrials.gov Identifier:
NCT01133184
First received: May 25, 2010
Last updated: June 16, 2010
Last verified: January 2010
  Purpose

Impaired activity of Natural Killer (NK) cells has been proposed as a mechanism contributing to viral persistence in Hepatitis C Virus (HCV) infection. NK cells display anti-fibrotic activities by killing activated hepatic stellate cells (HSCs) that have lost the self-recognition marker; Major Histocompatibility (MHC) class I. Determining the down-expressed genes on NK cells necessary for their anti-fibrotic activity was never studied previously. This will allow us to study their role fully in phagocytosis process as well as their interaction of HSCs and therefore manipulating these genes using molecular techniques. Exploring the cellular functions of these genes will highlight their involvement in the progression of liver fibrosis and could be used as a therapeutic tool for preventing the disease.


Condition Intervention Phase
Liver Fibrosis
Biological: Sci B vac
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-availability Study
Intervention Model: Factorial Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Prevention
Official Title: The Employing of the Bio-Hep-B PreS1/PreS2/S Hepatitis B Virus (HBV) Vaccine in New Born Babies From HBV Positive Palestinian Mothers

Resource links provided by NLM:


Further study details as provided by Hadassah Medical Organization:

Primary Outcome Measures:
  • Co-infection with Hepatitis D and HIV. [ Time Frame: 3 month ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 6343
Study Start Date: September 2010
Estimated Study Completion Date: September 2013
Estimated Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: Sci B vac
    Sci B vac
Detailed Description:

Lymphocyte/Hepatic stellate cells (HSCs) interactions via adhesion and phagocytosis are mediated as well as affected among others by Leptin, Endocannabinoids (CB) receptors, adiponectin, progesterone as well as by number of CD8 and NK related adhesion/phagocytosis candidate genes. Those pathways may explain the impaired activity of NK cells in Hepatitis C Virus (HCV)cirrhotic cases.

In this perspective, we propose the following specific aims:

  1. To confirm by repeated gene arrays the pro/anti-fibrotic genes expressed by NK and CD8 lymphocyte-subsets in human healthy volunteers and patients with HCV cirrhosis. Then to explore the same issue of lymphocyte gene array (NK and CD8 cells) in naïve and carbon tetrachloride fibrosis model in mice. Then to support results by the Real Time PCR and conduct bio-informatics assessments of results.
  2. Evaluate the role of Leptin, CB receptors and adiponectin in the lymphocyte/HSCs phagocytosis process. This would be tested both by in-vitro and in-vivo settings using cell cultures and knock-out mice (CB2-/-, Adiponectin-/- and leptin-/-Ob/Ob). The use of lymphocyte adoptive transfer model with immune manipulations will guide us for a specific functional role of each target gene in the specific lymphocyte subset.
  3. To evaluate how lymphocyte/HSC phagocytosis process affected by other CD8 and NK related gene candidates extrapolated from the results of earlier aims (see preliminary data). Suggested genes are including: Immune synapse genes (CHST13 and NLGN4X) to obtain the expected anti-fibrotic response. Genes with HSCs phagocytotic activity that is providing possible pathways for the HCV related escape from the expected anti-fibrotic response and eventually pro- fibrotic consequences (AIF1, CHST13, hnRPL). Killer cell lectin-like receptor subfamily C, member 2 (NKG2C; CD159c) is down expressed over HCV related CD8 cells suggesting a decrease of HSCs killing by the CD8 cells. Progestin & adipoQ receptor family member IV (PAQR4): Progesterone and adipoQ receptors are down-expressed over HCV related CD8 cells. Adiponectin is anti-fibrogenic mediator and is a candidate as PAQR4 ligand. When PAQR4 receptor is down- regulated in CD8 cells, it is suggested that this would be a mechanism for immune impairment. Also, Moreover, Progesterone and adipoQ receptors down- expression is supporting our mice animal model results that pregnancy caused progression of hepatic fibrogenesis associated with increased CD8 subsets and NK-T cells. We are going to evaluate the specific effect in the phagocytosis process.
  4. To evaluate if HCV by itself or HCV related proteins are directly responsible for the NK related impairment. Transgenic mice for the HCV envelop proteins will be used to assess alterations of lymphocyte subsets and phagocytosis ability.

The expected results will extend the knowledge of hepatic fibrogenesis in particular but may provide more application in general immunology. Therefore, expected results will be potentially a new target for anti-fibrotic designs and possibly in other medical conditions. Not only liver cirrhosis will be potentially prevented following anti-fibrotic therapies but also the hepatocellular carcinoma

  Eligibility

Ages Eligible for Study:   up to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • All Hepatitis B s Antigen (HBsAg) positive pregnant women attending the centers will be suggested to participate in the study and therefore provided with all information needed

Exclusion Criteria:

  • Co-infection with HIV
  • Mothers with immune suppression
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01133184

Contacts
Contact: Rifaat Safadi, M.D +972 2 6777337 Safadi@hadassah.org.il
Contact: Dieter Glebe, Ph.D +49 (0)641 9941246 dieter.glebe@viro.med.uni-giessen.de

Locations
Israel
Hadassah Medical Center
Jerusalem, Israel, 91120
Sponsors and Collaborators
Hadassah Medical Organization
Investigators
Principal Investigator: Rifaat Safadi, M.D Hadassah Medical Center
  More Information

No publications provided

Responsible Party: Dr. Rifaat Safadi, Hadassah Medical Center
ClinicalTrials.gov Identifier: NCT01133184     History of Changes
Other Study ID Numbers: 0509-08-HMO
Study First Received: May 25, 2010
Last Updated: June 16, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Hadassah Medical Organization:
HBV transmission PreS1/PreS2/S HBV vaccine

Additional relevant MeSH terms:
Fibrosis
Hepatitis
Hepatitis A
Hepatitis B
Liver Cirrhosis
Pathologic Processes
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections

ClinicalTrials.gov processed this record on August 26, 2014