Improving Fibrosis Outcomes With Metformin

Ottawa Hospital Research Institute

Status and phase

Withdrawn

Phase 2

Conditions

Hepatitis C

HIV Infection

Treatments

Drug: No metformin treatment

Drug: Metformin

Study type

Interventional

Funder types

Other

NETWORK

Identifiers

NCT02306070

CTNPT 019

Details and patient eligibility

About

This study will evaluate the role of Metformin on liver fibrosis in HCV-HIV co-infected and HCV mono-infected patients with insulin resistance receiving DAA HCV treatment.

Full description

HCV antiviral therapy has evolved rapidly in recent years and access to these medications has improved. While SVR is associated with improved liver outcomes, the rate of liver fibrosis regression with SVR is variable and predictors of regression are not well established. In addition, achieving SVR in patients with cirrhosis does not necessarily prevent decompensation or eliminate the risk of HCC. A better understanding of the role insulin resistance and impaired glucose metabolism have on these outcomes in HCV patients who achieve SVR are needed.

Identifying and targeting potentially modifiable risk factors such as IR may be of significant importance in preventing progression of and promoting regression of liver fibrosis, reducing mortality and improving outcomes for HCV-HIV co-infected and HCV-mono-infected patients.

This proposed pilot study will be the first to evaluate the role of Metformin on liver fibrosis in HCV-HIV co-infected and HCV mono-infected patients with IR receiving DAA HCV treatment.

If Metformin is effective in reducing liver fibrosis in this patient population, this will represent a well-tolerated, easy to administer, inexpensive therapy that will protect against negative HCV outcomes. This study will also be an opportunity to evaluate the impact of insulin resistance and hyperglycemia have on viral clearance HCV-infected patients treated with interferon-free regimens. In addition, the study will further explore the relationship between HCV, insulin resistance and AFP levels.

Sex

All

Ages

18 to 79 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Male or female, 18 to 79 years old inclusive
Provision of informed consent
Documented history of chronic HCV RNA infection
Intending to start on any 8-12 week IFN-free HCV antiviral therapy
If HIV-infected and not on HIV antiretroviral therapy, a CD4 count at least > 200
Insulin resistance as determined by a HOMA-IR of > 2.0 at screening
Evidence of fibrosis on FibroScan® > 8.0 kPa, OR liver biopsy score > 2 (Batts-Ludwig System) [55] (within 2 years)

Exclusion criteria

Pregnant, suspected to be pregnant, planning to become pregnant or breastfeeding
Chronic HBV infection
HbA1c > 8.0
Use of immune suppressing medications
Active malignancy
Current or any previous treatment with Metformin, other oral diabetes medications,insulin
Pre-existing diabetes (type 1, type 2 or gestational diabetes)
Clinical evidence of decompensated cirrhosis (ascites, esophageal varices, hepatic encephalopathy, hepatocellular carcinoma)
Presence of renal impairment or when renal function is not known, and also in patients with serum creatinine levels above upper limit of normal range. Renal disease or renal dysfunction (e.g., as suggested by serum creatinine levels >= 136 umol/L (males), >= 124 umol/L (females) or abnormal creatinine clearance (60 mL/min))
History of congestive heart failure requiring pharmacologic therapy
Wilson's disease
Alpha-1 antitrypsin
Hemochromatosis
Biliary Cirrhosis
Alcohol consumption > 50 g / day on average (see Appendix B for conversion to volume)
Participation in other clinical investigations during the study
History of lactic acidosis, irrespective of precipitating factors

Active illicit drug use and stable health illness will not be exclusionary assuming it is unlikely to compromise study adherence to protocol and study drug. In HIV-infected participants, HIV antiretroviral use and suppressed HIV viral load will not be required for participation.

HCV antiviral therapy will not be withheld for any participant that is eligible and desires to start treatment. If HCV treatment is anticipated to be started during the 48-week period of assessment, then participants will not be enrolled.