Improving Fibrosis Outcomes With Metformin

Hepatitis C Clinical Trial

Official title:

Improving Treatment and Liver Fibrosis Outcomes With Metformin in HCV-HIV Co-infected and HCV Mono-infected Patients With Insulin Resistance.

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02306070
• Other study ID #: CTNPT 019
• Status: Withdrawn
• Phase: Phase 2
• First received: November 2, 2014
• Last updated: April 13, 2018
• Start date: January 2016
• Est. completion date: April 3, 2018

Study information

• Verified date: September 2017
• Source: Ottawa Hospital Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: April 3, 2018
• Est. primary completion date: September 30, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

Inclusion Criteria:

1. Male or female, 18 to 79 years old inclusive

2. Provision of informed consent

3. Documented history of chronic HCV RNA infection

4. Intending to start on any 8-12 week IFN-free HCV antiviral therapy

5. If HIV-infected and not on HIV antiretroviral therapy, a CD4 count at least > 200

6. Insulin resistance as determined by a HOMA-IR of > 2.0 at screening

7. Evidence of fibrosis on FibroScan® > 8.0 kPa, OR liver biopsy score > 2 (Batts-Ludwig System) [55] (within 2 years)

Exclusion Criteria:

1. Pregnant, suspected to be pregnant, planning to become pregnant or breastfeeding

2. Chronic HBV infection

3. HbA1c > 8.0

4. Use of immune suppressing medications

5. Active malignancy

6. Current or any previous treatment with Metformin, other oral diabetes medications,insulin

7. Pre-existing diabetes (type 1, type 2 or gestational diabetes)

8. Clinical evidence of decompensated cirrhosis (ascites, esophageal varices, hepatic encephalopathy, hepatocellular carcinoma)

9. 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))

10. History of congestive heart failure requiring pharmacologic therapy

11. Wilson's disease

12. Alpha-1 antitrypsin

13. Hemochromatosis

14. Biliary Cirrhosis

15. Alcohol consumption > 50 g / day on average (see Appendix B for conversion to volume)

16. Participation in other clinical investigations during the study

17. 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.

Related Conditions & MeSH terms

• Hepatitis C
• HIV Infection
• HIV Infections

Intervention

Drug:
• Metformin
metformin treatment + standard of care dietary and exercise advice
• No metformin treatment
no metformin treatment + standard of care dietary and exercise advice

Locations

Country	Name	City	State
Canada	The Ottawa Hospital, General Campus	Ottawa	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Ottawa Hospital Research Institute	CIHR Canadian HIV Trials Network

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in FibroScan® score (kPa) from baseline to week 12 (start of HCV treatment), compared between treatment groups.	liver elastography score (kPa)	12 weeks
Secondary	Virological response rates (SVR 12 weeks post HCV antiviral therapy) between treatment groups.	HCV RNA level (IU/mL)	12 weeks
Secondary	Change in APRI measurements from baseline compared between treatment groups.	calculated APRI	12, 24, 48weeks
Secondary	Change from baseline in glucose metabolism (HOMA-IR, fasting insulin, glucose levels)	fasting glucose and insulin	4, 8, 12, 24, 36, 48 weeks
Secondary	Changes from baseline in lipid levels	fasting total cholesterol, LDL-c, HDL-c, triglycerides	12, 36, 48 weeks
Secondary	Changes from baseline in anthropometric measures	waist circumference, body weight and BMI	4, 8, 12, 24, 36, 48 weeks
Secondary	Changes from baseline in liver-related inflammatory markers	IL-6, IL-8, TNF-alpha, TGF-beta, C-reactive protein	4, 8, 12, 24, 36 weeks
Secondary	Changes in AFP levels from baseline	AFP	12, 24, 36, 48 weeks
Secondary	Participant acceptability to study medication dosing (in Arm 1 only)	Participant acceptability will be evaluated in Arm 1 only using the Treatment Satisfaction Questionnaire for Medication (TSQM), Version 1.4	8, 24, 48 weeks
Secondary	Changes from baseline in diet	Changes in diet from baseline will be captured using the International Physical Activity Questionnaire short-form (IPAQ-sf)	24, 48 weeks
Secondary	Changes from baseline in physical exercise parameters	Changes in physical activity from baseline will be captured using the International Physical Activity Questionnaire short-form (IPAQ-sf)	24, 48 weeks

External Links

•   CIHR Canadian HIV Trials Network