Improving Fibrosis Outcomes With Metformin

NCT ID: NCT02306070

Last Updated: 2018-04-17

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2018-04-03

Brief 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.

Detailed 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.

Conditions

HIV Infection; Hepatitis C

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Metformin + lifestyle modification

Metformin + lifestyle modification pre, during and post HCV antiviral therapy

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

metformin treatment + standard of care dietary and exercise advice

No Metformin + Lifestyle modification

No metformin + lifestyle modification pre, during and post HCV antiviral therapy.

Group Type: PLACEBO_COMPARATOR

No metformin treatment

Intervention Type: DRUG

no metformin treatment + standard of care dietary and exercise advice

Interventions

Metformin

metformin treatment + standard of care dietary and exercise advice

Intervention Type: DRUG

No metformin treatment

no metformin treatment + standard of care dietary and exercise advice

Intervention Type: DRUG

Other Intervention Names

lifestyle modification; lifestyle modification

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CIHR Canadian HIV Trials Network

NETWORK

Sponsor Role: collaborator

Ottawa Hospital Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Curtis Cooper, MD

Role: PRINCIPAL_INVESTIGATOR

The Ottawa Hospital Division of Infectious Diseases

Locations

The Ottawa Hospital, General Campus

Ottawa, Ontario, Canada

Countries

Canada

References

Doyle MA, Singer J, Lee T, Muir M, Cooper C. Improving treatment and liver fibrosis outcomes with metformin in HCV-HIV co-infected and HCV mono-infected patients with insulin resistance: study protocol for a randomized controlled trial. Trials. 2016 Jul 20;17(1):331. doi: 10.1186/s13063-016-1454-6.

Reference Type: DERIVED

PMID: 27439433 (View on PubMed)

Related Links

http://www.hivnet.ubc.ca/home/

CIHR Canadian HIV Trials Network

Other Identifiers

CTNPT 019

Identifier Type: -

Identifier Source: org_study_id