Back to resultsImproving Fibrosis Outcomes With Metformin
Primary Purpose
HIV Infection, Hepatitis C
Status
Withdrawn
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Metformin
No metformin treatment
Sponsored by
About this trial
This is an interventional treatment trial for HIV Infection
Eligibility Criteria
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.
Sites / Locations
- The Ottawa Hospital, General Campus
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Metformin + lifestyle modification
No Metformin + Lifestyle modification
Arm Description
Metformin + lifestyle modification pre, during and post HCV antiviral therapy
No metformin + lifestyle modification pre, during and post HCV antiviral therapy.
Outcomes
Primary Outcome Measures
Change in FibroScan® score (kPa) from baseline to week 12 (start of HCV treatment), compared between treatment groups.
liver elastography score (kPa)
Secondary Outcome Measures
Virological response rates (SVR 12 weeks post HCV antiviral therapy) between treatment groups.
HCV RNA level (IU/mL)
Change in APRI measurements from baseline compared between treatment groups.
calculated APRI
Change from baseline in glucose metabolism (HOMA-IR, fasting insulin, glucose levels)
fasting glucose and insulin
Changes from baseline in lipid levels
fasting total cholesterol, LDL-c, HDL-c, triglycerides
Changes from baseline in anthropometric measures
waist circumference, body weight and BMI
Changes from baseline in liver-related inflammatory markers
IL-6, IL-8, TNF-alpha, TGF-beta, C-reactive protein
Changes in AFP levels from baseline
AFP
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
Changes from baseline in diet
Changes in diet from baseline will be captured using the International Physical Activity Questionnaire short-form (IPAQ-sf)
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)
Full Information
NCT ID
NCT02306070
First Posted
November 2, 2014
Last Updated
April 13, 2018
Sponsor
Ottawa Hospital Research Institute
Collaborators
CIHR Canadian HIV Trials Network
1. Study Identification
Unique Protocol Identification Number
NCT02306070
Brief Title
Improving Fibrosis Outcomes With Metformin
Official Title
Improving Treatment and Liver Fibrosis Outcomes With Metformin in HCV-HIV Co-infected and HCV Mono-infected Patients With Insulin Resistance.
Study Type
Interventional
2. Study Status
Record Verification Date
September 2017
Overall Recruitment Status
Withdrawn
Why Stopped
insufficient funding
Study Start Date
January 2016 (undefined)
Primary Completion Date
September 30, 2017 (Actual)
Study Completion Date
April 3, 2018 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ottawa Hospital Research Institute
Collaborators
CIHR Canadian HIV Trials Network
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infection, Hepatitis C
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Metformin + lifestyle modification
Arm Type
Experimental
Arm Description
Metformin + lifestyle modification pre, during and post HCV antiviral therapy
Arm Title
No Metformin + Lifestyle modification
Arm Type
Placebo Comparator
Arm Description
No metformin + lifestyle modification pre, during and post HCV antiviral therapy.
Intervention Type
Drug
Intervention Name(s)
Metformin
Other Intervention Name(s)
lifestyle modification
Intervention Description
metformin treatment + standard of care dietary and exercise advice
Intervention Type
Drug
Intervention Name(s)
No metformin treatment
Other Intervention Name(s)
lifestyle modification
Intervention Description
no metformin treatment + standard of care dietary and exercise advice
Primary Outcome Measure Information:
Title
Change in FibroScan® score (kPa) from baseline to week 12 (start of HCV treatment), compared between treatment groups.
Description
liver elastography score (kPa)
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Virological response rates (SVR 12 weeks post HCV antiviral therapy) between treatment groups.
Description
HCV RNA level (IU/mL)
Time Frame
12 weeks
Title
Change in APRI measurements from baseline compared between treatment groups.
Description
calculated APRI
Time Frame
12, 24, 48weeks
Title
Change from baseline in glucose metabolism (HOMA-IR, fasting insulin, glucose levels)
Description
fasting glucose and insulin
Time Frame
4, 8, 12, 24, 36, 48 weeks
Title
Changes from baseline in lipid levels
Description
fasting total cholesterol, LDL-c, HDL-c, triglycerides
Time Frame
12, 36, 48 weeks
Title
Changes from baseline in anthropometric measures
Description
waist circumference, body weight and BMI
Time Frame
4, 8, 12, 24, 36, 48 weeks
Title
Changes from baseline in liver-related inflammatory markers
Description
IL-6, IL-8, TNF-alpha, TGF-beta, C-reactive protein
Time Frame
4, 8, 12, 24, 36 weeks
Title
Changes in AFP levels from baseline
Description
AFP
Time Frame
12, 24, 36, 48 weeks
Title
Participant acceptability to study medication dosing (in Arm 1 only)
Description
Participant acceptability will be evaluated in Arm 1 only using the Treatment Satisfaction Questionnaire for Medication (TSQM), Version 1.4
Time Frame
8, 24, 48 weeks
Title
Changes from baseline in diet
Description
Changes in diet from baseline will be captured using the International Physical Activity Questionnaire short-form (IPAQ-sf)
Time Frame
24, 48 weeks
Title
Changes from baseline in physical exercise parameters
Description
Changes in physical activity from baseline will be captured using the International Physical Activity Questionnaire short-form (IPAQ-sf)
Time Frame
24, 48 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Curtis Cooper, MD
Organizational Affiliation
The Ottawa Hospital Division of Infectious Diseases
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Ottawa Hospital, General Campus
City
Ottawa
State/Province
Ontario
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
27439433
Citation
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.
Results Reference
derived
Links:
URL
http://www.hivnet.ubc.ca/home/
Description
CIHR Canadian HIV Trials Network
Learn more about this trial
Improving Fibrosis Outcomes With Metformin
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