Clinical trial NCT00322179: Microarray Analysis of IFN-Induced Gene Expression in Obese and Non-Obese Patients With Chronic Hepatitis C
Official title: Microarray Analysis of IFN-Induced Gene Expression in Obese and Non-Obese Patients With Chronic Hepatitis C
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Chronic Hepatitis C
Obesity
Keywords: Microarray Analysis
Obesity
Chronic Hepatitis C
Lead sponsor: Palo Alto Veterans Institute for Research
Sponsor class: OTHER
Collaborators: name: Hoffmann-La Roche
First posted: 2006-05-05
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: OTHER
Study population: Inclusion Criteria:

* obese (weight \> 85kg and BMI\>30) or non-obese patients (\<75kg and BMI \<25) with chronic Hepatitis C
* Chronic Hepatitis C infection with documented HCV RNA
* Body habitat either as obese or non-obese as defined above
* Currently not under IFN therapy
* Non-African American

Brief summary: The response rate to interferon-based anti-viral therapy for chronic hepatitis C is lower in patients who are obese. However, it is not clear whether this is related to suboptimal dosing of the medication or alterated response in obese patients. Alterated immune response had been reported in obese patients. The goal of current study is to determine the immune response to interferon in obese compared to non-obese chronic hepatitis C in an tissue culture system.

Detailed description: To examine our hypothesis, we will incubate PBMC samples from obese and nonobese patients with IFN, followed by microarray analysis to compare the IFN response patterns in both groups of patients and to identify genes differentially regulated between these two groups. Identification of such genes will provide important insight to the mechanism of the antiviral effect of HCV. The identified genes will have the potential of serving as targets for pharmaceutical intervention aiming at enhancing the efficacy of IFN therapy for obese patients.

This is an open-label study. Ten obese and 10 nonobese patients with chronic hepatitis C will be recruited. For the purpose of this study, obese is defined as body weight \>85 kg and BMI \>30, and nonobese as body weight \<75 kg and BMI\<25.

Eligibility criteria: Inclusion Criteria:

* obese (weight \> 85kg and BMI\>30) or non-obese patients (\<75kg and BMI \<25) with chronic Hepatitis C
* Chronic Hepatitis C infection with documented HCV RNA
* Body habitat either as obese or non-obese as defined above
* Currently not under IFN therapy
* Non-African American

Exclusion Criteria:

* Body habitat neither obese or non-obese as defined for the purpose of this study
* Unable to give consent
* On immunomodulatory agents such as prednisone
* Active infection other than Hepatitis C
* Co-infection with HBV or HIV
* Active or excessive alcohol use
* Other cause of chronic Hepatitis

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: VA Palo Alto Health Care System
state: California
Study officials:
affiliation: VA Palo Alto Health Care System
name: Ramsey Cheung, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bressler BL, Guindi M, Tomlinson G, Heathcote J. High body mass index is an independent risk factor for nonresponse to antiviral treatment in chronic hepatitis C. Hepatology. 2003 Sep;38(3):639-44. doi: 10.1053/jhep.2003.50350.
citation: Camps J, Crisostomo S, Garcia-Granero M, Riezu-Boj JI, Civeira MP, Prieto J. Prediction of the response of chronic hepatitis C to interferon alfa: a statistical analysis of pretreatment variables. Gut. 1993 Dec;34(12):1714-7. doi: 10.1136/gut.34.12.1714.
citation: Farooqi IS, Matarese G, Lord GM, Keogh JM, Lawrence E, Agwu C, Sanna V, Jebb SA, Perna F, Fontana S, Lechler RI, DePaoli AM, O'Rahilly S. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest. 2002 Oct;110(8):1093-103. doi: 10.1172/JCI15693.
citation: Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, Haussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002 Sep 26;347(13):975-82. doi: 10.1056/NEJMoa020047.
citation: Ji X, Cheung R, Cooper S, Li Q, Greenberg HB, He XS. Interferon alfa regulated gene expression in patients initiating interferon treatment for chronic hepatitis C. Hepatology. 2003 Mar;37(3):610-21. doi: 10.1053/jhep.2003.50105.