Insulin Resistance in HCV Infection

Insulin Resistance Clinical Trial

Official title:

Impact of Hepatitis C on Insulin Sensitivity and Insulin Secretion in Latinos

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01858012
• Other study ID #: UCSF 10-00922
• Status: Active, not recruiting
• Start date: January 1, 2008
• Est. completion date: December 31, 2026

Study information

• Verified date: January 2024
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The study hypothesis is that the means by which HCV induces glucose intolerance is through impairment of B-cell function and compensatory hyperinsulinemia in predisposed Latinos with insulin resistance and that HCV eradication improves these abnormalities. It is also hypothesized that moderate alcohol consumption impact insulin sensitivity and secretion with Latinos with or without HCV infection.

Description:

The study hypothesis is that the means by which HCV induces glucose intolerance is through impairment of B-cell function and compensatory hyperinsulinemia in predisposed Latinos with insulin resistance and that HCV eradication improves these abnormalities. This study addresses changes in the metabolic parameters over time. In addition, it is hypothesized that moderate alcohol consumption impacts insulin resistance and secretion and 30 patients with or without HCV who drink alcohol moderately will have discontinuation of alcohol use for 6 weeks and have metabolic testing before and after alcohol discontinuation.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 250
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion criteria for HCV participants:

• Male or female patients between 18 and 60 years of age

• Body mass index (BMI) > 20 Kg/m2

• Serologic evidence of hepatitis C infection by anti-HCV antibody

• Detectable plasma HCV-RNA

• Compensated liver disease with the following minimum biochemical parameters:

prothrombin time < 2 seconds prolonged compared to control and bilirubin < 3 mg/dL

• Willingness to provide informed consent

Inclusion criteria for healthy Latino volunteers (without HCV infection):

-Same inclusion criteria as above except no evidence of HCV infection (anti-HCV antibody negative)

Inclusion criteria for participation in 6-week alcohol abstinence follow-up testing:

-Latinos who are moderate1 alcohol drinkers (1NIAAA definition: female: no more than 3 drinks on any day & no more than 7 drinks per week; male: no more than 4 drinks on any day and no more than 14 drinks per week).

Steady-State Plasma Glucose < 180 mg/dL

Exclusion criteria:

• Hepatitis B or HIV infection

• Subjects with liver disease other than that caused by HCV

• Known history of diabetes, or fasting plasma glucose concentration >126 mg/dl

• Known history of cirrhosis of the liver, as well as individuals with decompensated liver disease such as those with ascites, variceal bleeding, and encephalopathy

• Known history of pancreatitis

• Prior or current treatment for HCV

• Heavy alcohol use (>80 g/d)

• Subjects of lipid lowering agents, steroid/ anabolic therapy

• Significant medical illness that would interfere with the completion of the study

Exclusion criteria for healthy (non HCV) Latino volunteers:

-Same as above, including subjects with HCV infection

Related Conditions & MeSH terms

• Insulin Resistance

Intervention

Behavioral:
• Moderate alcohol cessation
patients will have moderate alcohol use discontinued for 6 weeks and have before and after alcohol cessation clinical and metabolic assessment and also patients with hepatitis C who have undergo therapy for hepatitis C may have repeat clinical and metabolic assessement

Locations

Country	Name	City	State
United States	University of california San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Francisco

Country where clinical trial is conducted

United States, 

References & Publications (10)

Brandman D, Bacchetti P, Ayala CE, Maher JJ, Khalili M. Impact of insulin resistance on HCV treatment response and impact of HCV treatment on insulin sensitivity using direct measurements of insulin action. Diabetes Care. 2012 May;35(5):1090-4. doi: 10.23 — View Citation

Burman BE, Bacchetti P, Ayala CE, Gelman N, Melgar J, Khalili M. Liver inflammation is a risk factor for prediabetes in at-risk latinos with and without hepatitis C infection. Liver Int. 2015 Jan;35(1):101-7. doi: 10.1111/liv.12676. Epub 2014 Sep 20. — View Citation

Burman BE, Bacchetti P, Khalili M. Moderate Alcohol Use and Insulin Action in Chronic Hepatitis C Infection. Dig Dis Sci. 2016 Aug;61(8):2417-2425. doi: 10.1007/s10620-016-4119-0. Epub 2016 Mar 23. — View Citation

Gonzales CA, Bacchetti P, Khalili M. Impact of gender and menopausal status on metabolic parameters in chronic hepatitis C infection. J Viral Hepat. 2016 Mar;23(3):232-9. doi: 10.1111/jvh.12487. Epub 2015 Nov 10. — View Citation

Kim RG, Kramer-Feldman J, Bacchetti P, Grimes B, Burchard E, Eng C, Hu D, Hellerstein M, Khalili M. Disentangling the impact of alcohol use and hepatitis C on insulin action in Latino individuals. Alcohol Clin Exp Res. 2022 Jan;46(1):87-99. doi: 10.1111/a — View Citation

Lam KD, Bacchetti P, Abbasi F, Ayala CE, Loeb SM, Shah V, Wen MJ, Reaven GM, Maher JJ, Khalili M. Comparison of surrogate and direct measurement of insulin resistance in chronic hepatitis C virus infection: impact of obesity and ethnicity. Hepatology. 201 — View Citation

Mukhtar NA, Ayala C, Maher JJ, Khalili M. Assessment of factors associated with pre-diabetes in HCV infection including direct and dynamic measurements of insulin action. J Viral Hepat. 2012 Jul;19(7):480-7. doi: 10.1111/j.1365-2893.2011.01568.x. Epub 201 — View Citation

Mukhtar NA, Bacchetti P, Ayala CE, Melgar J, Christensen S, Maher JJ, Khalili M. Insulin sensitivity and variability in hepatitis C virus infection using direct measurement. Dig Dis Sci. 2013 Apr;58(4):1141-8. doi: 10.1007/s10620-012-2438-3. Epub 2012 Oct — View Citation

Shah SC, Kornak J, Khalili M. Depression is not associated with peripheral insulin resistance in patients with chronic hepatitis C infection. J Viral Hepat. 2015 Mar;22(3):272-80. doi: 10.1111/jvh.12306. Epub 2014 Sep 8. — View Citation

Uribe LA, Bacchetti P, Gelman N, Burchard E, Fitch M, Hellerstein M, Khalili M. Impact of Moderate Alcohol Discontinuation on Insulin Action and Secretion in Latinos With and Without Hepatitis C. Alcohol Clin Exp Res. 2018 Mar;42(3):492-499. doi: 10.1111/ — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	insulin resistance	steady state plasma glucose level (mg/dL)	baseline, 6 weeks and 18 months
Secondary	Insulin secretion	insulin secretion rate area under the curve (pmol/min)	baseline, 6 weeks and 18 months