Examining the Immune Response in Patients With Gaucher Disease and Hepatitis B or C

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2011 by Shaare Zedek Medical Center.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Shaare Zedek Medical Center
ClinicalTrials.gov Identifier:
NCT01274208
First received: January 10, 2011
Last updated: NA
Last verified: January 2011
History: No changes posted
  Purpose

Study objectives:

  • Investigate the anti-HCV or HBV immune response in patients with GD
  • Define the potential role of high levels of Glucocerebroside in the immune system

Study hypothesis:

High levels of Glucocerebroside can be used as a tool in the antiviral treatment of hepatitis B or C by potentiating the immune response of natural killer T cells and dendritic cells


Condition
Gaucher Disease
Hepatitis B
Hepatitis C

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Enhanced HCV NS3-specific T Cell Proliferation, IFNγ and IL-10 Secreting Clones, and Peripheral Blood NKT Cells in Patients With Type I Gaucher Disease Infected With HCV or HBV: An Advantage in Anti Hepatitis Immunity?

Resource links provided by NLM:


Further study details as provided by Shaare Zedek Medical Center:

Primary Outcome Measures:
  • The anti-HCV or HBV immune response in patients with Gaucher Disease [ Time Frame: 30 days ] [ Designated as safety issue: No ]

    the immune response will be measured by:

    1. Enhanced HCV NS3-specific T cell proliferation
    2. IFNγ and IL-10 secreting clones by ELISPOT assay
    3. Peripheral blood NKT cells(CD3+,CD56+)by FACS analysis
    4. Measurement of serum IL-2, IL-6, IL-10, and TGFβ levels infected with HCV or HBV


Secondary Outcome Measures:
  • the role Glucocerebroside level have by enhanced immunity in patients with Gaucher disease [ Time Frame: 30 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 80
Study Start Date: January 2011
Estimated Study Completion Date: April 2011
Estimated Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts
Gaucher Disease with Hepatitis B or C

Detailed Description:

Gaucher disease is the most common glycolipid storage disorder, caused by reduced activity of the lysosomal enzyme glucocerebrosidase, which leads to the accumulation of the substrate, glucocerebroside (GC), in the cells of the reticulo-endothelial system.

One of the hallmarks of GD is its great phenotypic heterogeneity with variable presentations and symptoms, beginning with a lethal variant of infants dying at or near birth with hydrops fetalis and ichthyoids at one extreme and totally asymptomatic individuals without any physical or laboratory abnormalities at the other extreme.

This autosomal recessive disease is pan-ethnic, but it is especially prevalent among Ashkenazi Jews. From over 300 different mutations reported in the glucocerebrosidase gene, five account for 98% of the disease-producing alleles. Of these mutations, N370S (or 1226G) occurs in 1 out of 17 Ashkenazi individuals, leading to a disease frequency of 1:850 in this ethnic group.

The high prevalence of more than a single mutation among Ashkenazi Jews and the existence of two additional rare inherited lysosomal glycolipid storage diseases, Tay Sachs and Nieman Pick, at a higher prevalence within the same ethnic group is believed to be caused by selective advantage.

Available genetic data are consistent with a founder effect(4) whereas the nature of such an advantage has not been identified.

The aim of this study was to investigate the anti-HCV or HBV immune response in patients with GD in an attempt to define the potential role of high levels of GC in the immune system and antiviral immunity.

Study importance:

The host metabolic background exerts a profound effect on antiviral immunity, which may influence the clinical course of chronic HCV or HBV infection The accumulation of GC in patients with GD may provide a selective evolutionary advantage to these patients.

Glucocerebroside was recently tested in human trials and shown to be effective in altering NKT- dependent metabolic pathways, insulin resistance, and associated liver injury.

The present study examine the capability of Glucocerebroside to be be used as a tool in the antiviral treatment of hepatitis B or C by potentiating the immune response of natural killer T cells and dendritic cells.

Statistical Analysis:

Data are presented as the mean ± SD. The Kruskal Wallis non-parametric ANOVA test was used to identify differences between the study groups.

The student t-test and non-parametric Mann-Whitney test were used to compare quantitative variables between the study groups as appropriate; P <0.05 was considered to be significant.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

Patients with Gaucher Disease were recruited from the Sha'are Zedek Gaucher disease clinic, a national referral center for the disease.

Criteria

Inclusion Criteria:

  • Patients with Gaucher disease
  • Patients with hepatitis B or C without Gaucher disease
  • Individuals or patients without Gaucher disease and hepatitis B or C
  • Individuals or patients who signed an approval for the research
  • Men and women 18< years of age , pregnant women

Exclusion Criteria:

  • Inabillity to give an approval for the research
  • Acute liver disease that can alter the lab results , such as: Rt. CHF ,

severe infection ,inflammation, medication such as : Statins , Isoniazid ,

Amiodarone

- Patients who received treatment for hepatitis B or C such as: Interferon ,

Pegylated interferon , Ribavirin , Adenovir, Entecavir .

-

  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: NCT01274208

Contacts
Contact: Bernardo Melamud, Dr. 972-508685845 dr.bernardo@gmail.com
Contact: Ari Zimran, Prof. 972-2-65555143 azimran@gmail.com

Locations
Israel
Hadassah Medical Center Recruiting
Jerusalem, Israel
Contact: Yaron Ilan, Prof.    972 2 6778231    ilan@hadassah.org.il   
Sub-Investigator: Yaron Ilan, Prof.         
Shaare Zedek , Medical Center Recruiting
Jerusalem, Israel, 91120
Contact: Melamud       dr.bernardo@gmail.com   
Contact: zimran, Prof.       azimran@gmail.com   
Principal Investigator: Bernardo Melamud, Dr.         
Sub-Investigator: Ari Zimran, Prof.         
Sponsors and Collaborators
Shaare Zedek Medical Center
Investigators
Principal Investigator: Bernardo Melamud, Dr. Gaucher Clinic , Shaare zedek Hospital
  More Information

Additional Information:
Publications:
Responsible Party: Dr. Bernardo Melamud, Prof' Ari Zimran , Gaucher Clinic , Shaare Zedek Hospital
ClinicalTrials.gov Identifier: NCT01274208     History of Changes
Other Study ID Numbers: SZMC- 89/10
Study First Received: January 10, 2011
Last Updated: January 10, 2011
Health Authority: Israel: Ethics Commission

Keywords provided by Shaare Zedek Medical Center:
Gaucher disease Hepatitis Glucocerebroside immunity

Additional relevant MeSH terms:
Brain Diseases, Metabolic, Inborn
Gaucher Disease
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis C
Brain Diseases
Brain Diseases, Metabolic
Central Nervous System Diseases
Digestive System Diseases
DNA Virus Infections
Enterovirus Infections
Flaviviridae Infections
Genetic Diseases, Inborn
Hepadnaviridae Infections
Hepatitis, Viral, Human
Lipid Metabolism Disorders
Lipid Metabolism, Inborn Errors
Lipidoses
Liver Diseases
Lysosomal Storage Diseases
Lysosomal Storage Diseases, Nervous System
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases
Picornaviridae Infections
RNA Virus Infections
Sphingolipidoses
Virus Diseases

ClinicalTrials.gov processed this record on October 21, 2014