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

Hepatitis C Clinical Trial

Official title:

Enhanced HCV Nonstructural Protein 3 (NS3) -Specific T Cell Proliferation,Interferon γ (IFNγ) and Interleukin-10 (IL-10) Secreting Clones, and Peripheral Blood Natural Killers T Cells ( NKT Cells) in Patients With Type I Gaucher Disease Infected With HCV : An Advantage in Anti Hepatitis Immunity?

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01274208
• Other study ID #: SZMC- 89/10
• Status: Recruiting
• Phase: N/A
• First received: January 10, 2011
• Last updated: November 18, 2014
• Start date: January 2011
• Est. completion date: April 2016

Study information

• Verified date: November 2014
• Source: Shaare Zedek Medical Center
• Contact: Bernardo Melamud, Dr.
• Phone: 972-508685845
• Email: dr.bernardo[@]gmail.com
• Is FDA regulated: No
• Health authority: Israel: Ethics Commission
• Study type: Observational

Clinical Trial Summary

Study objectives:

• Investigate the anti-HCV response in patients with Gaucher disease(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 C by potentiating the immune response of natural killer T cells and dendritic cells

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 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 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 C by potentiating the immune response of natural killer T cells and dendritic cells.

Statistical Analysis:

Data are presented as the mean ± standard deviation (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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: April 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

• Patients with Gaucher disease

• Patients with hepatitis C without Gaucher disease

• Individuals or patients without Gaucher disease and hepatitis 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. congestive heart failure

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

Amiodarone

• Patients who received treatment for hepatitis C such as: Interferon ,

Pegylated interferon , Ribavirin

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Gaucher Disease
• Hepatitis
• Hepatitis A
• Hepatitis C

Locations

Country	Name	City	State
Israel	Hadassah Medical Center	Jerusalem
Israel	Shaare Zedek , Medical Center	Jerusalem

Sponsors (1)

Lead Sponsor	Collaborator
Shaare Zedek Medical Center

Country where clinical trial is conducted

Israel, 

References & Publications (6)

Beutler E. Gaucher disease as a paradigm of current issues regarding single gene mutations of humans. Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5384-90. Review. — View Citation

Beutler E. Gaucher disease: multiple lessons from a single gene disorder. Acta Paediatr Suppl. 2006 Apr;95(451):103-9. Review. — View Citation

Butters TD. Gaucher disease. Curr Opin Chem Biol. 2007 Aug;11(4):412-8. Epub 2007 Jul 23. Review. — View Citation

Elstein D, Abrahamov A, Hadas-Halpern I, Zimran A. Gaucher's disease. Lancet. 2001 Jul 28;358(9278):324-7. — View Citation

Slatkin M. A population-genetic test of founder effects and implications for Ashkenazi Jewish diseases. Am J Hum Genet. 2004 Aug;75(2):282-93. Epub 2004 Jun 18. — View Citation

Zigmond E LG, Pappo O, Zangen S, Levy Sklair M, Hemed N, Rabbani E, Itamar R, Ilan Y, Margalit M. Treatment of non-alcoholic steatohepatitis by B-glucosylceramide: A phase I/II clinical study. Hepatology 2006;44 .180A, .

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Gaucher patients' immune system provide enhanced immunity against hepatitis c virus		6 months	No
Secondary	the role Glucocerebroside level have by enhanced immunity in patients with Gaucher disease		30 days	No

External Links

•   Shaare Zedek Medical Center site