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

NCT ID: NCT01274208

Last Updated: 2014-11-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

80 participants

Study Classification

OBSERVATIONAL

Study Start Date

2011-01-31

Study Completion Date

2016-04-30

Brief Summary

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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

Detailed Description

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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.

Conditions

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Gaucher Disease Hepatitis C

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Gaucher Disease with Hepatitis C

No interventions assigned to this group

Eligibility Criteria

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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

\-
Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Shaare Zedek Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Ari Zimran

Prof. Ari Zimran

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Bernardo Melamud, Dr.

Role: PRINCIPAL_INVESTIGATOR

Gaucher Clinic , Shaare zedek Hospital

Locations

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Shaare Zedek , Medical Center

Jerusalem, , Israel

Site Status RECRUITING

Hadassah Medical Center

Jerusalem, , Israel

Site Status RECRUITING

Countries

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Israel

Central Contacts

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Bernardo Melamud, Dr.

Role: CONTACT

972-508685845

Ari Zimran, Prof.

Role: CONTACT

972-2-65555143

Facility Contacts

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Melamud

Role: primary

zimran, Prof.

Role: backup

Yaron Ilan, Prof.

Role: primary

972 2 6778231

References

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Elstein D, Abrahamov A, Hadas-Halpern I, Zimran A. Gaucher's disease. Lancet. 2001 Jul 28;358(9278):324-7. doi: 10.1016/S0140-6736(01)05490-3. No abstract available.

Reference Type BACKGROUND
PMID: 11498237 (View on PubMed)

Butters TD. Gaucher disease. Curr Opin Chem Biol. 2007 Aug;11(4):412-8. doi: 10.1016/j.cbpa.2007.05.035. Epub 2007 Jul 23.

Reference Type BACKGROUND
PMID: 17644022 (View on PubMed)

Beutler E. Gaucher disease: multiple lessons from a single gene disorder. Acta Paediatr Suppl. 2006 Apr;95(451):103-9. doi: 10.1111/j.1651-2227.2006.tb02398.x.

Reference Type BACKGROUND
PMID: 16720474 (View on PubMed)

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. doi: 10.1086/423146. Epub 2004 Jun 18.

Reference Type BACKGROUND
PMID: 15208782 (View on PubMed)

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. doi: 10.1073/pnas.90.12.5384.

Reference Type BACKGROUND
PMID: 8516282 (View on PubMed)

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, .

Reference Type RESULT

Other Identifiers

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SZMC- 89/10

Identifier Type: -

Identifier Source: org_study_id