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Trial record 1 of 47 for:    Improving outcomes with Metformin
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Improving Fibrosis Outcomes With Metformin

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ClinicalTrials.gov Identifier: NCT02306070
Recruitment Status : Withdrawn (insufficient funding)
First Posted : December 3, 2014
Last Update Posted : April 17, 2018
Sponsor:
Collaborator:
CIHR Canadian HIV Trials Network
Information provided by (Responsible Party):
Ottawa Hospital Research Institute

Study Description
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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.

Condition or disease Intervention/treatment Phase
HIV Infection Hepatitis C Drug: Metformin Drug: No metformin treatment Phase 2

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Improving Treatment and Liver Fibrosis Outcomes With Metformin in HCV-HIV Co-infected and HCV Mono-infected Patients With Insulin Resistance.
Study Start Date : January 2016
Actual Primary Completion Date : September 30, 2017
Estimated Study Completion Date : April 3, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arms and Interventions
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Arm Intervention/treatment
Experimental: Metformin + lifestyle modification
Metformin + lifestyle modification pre, during and post HCV antiviral therapy
 Drug: Metformin
metformin treatment + standard of care dietary and exercise advice
Other Name: lifestyle modification
Placebo Comparator: No Metformin + Lifestyle modification
No metformin + lifestyle modification pre, during and post HCV antiviral therapy.
 Drug: No metformin treatment
no metformin treatment + standard of care dietary and exercise advice
Other Name: lifestyle modification


Outcome Measures
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Primary Outcome Measures :
  1. Change in FibroScan® score (kPa) from baseline to week 12 (start of HCV treatment), compared between treatment groups. [ Time Frame: 12 weeks ]
    liver elastography score (kPa)


Secondary Outcome Measures :
  1. Virological response rates (SVR 12 weeks post HCV antiviral therapy) between treatment groups. [ Time Frame: 12 weeks ]
    HCV RNA level (IU/mL)

  2. Change in APRI measurements from baseline compared between treatment groups. [ Time Frame: 12, 24, 48weeks ]
    calculated APRI

  3. Change from baseline in glucose metabolism (HOMA-IR, fasting insulin, glucose levels) [ Time Frame: 4, 8, 12, 24, 36, 48 weeks ]
    fasting glucose and insulin

  4. Changes from baseline in lipid levels [ Time Frame: 12, 36, 48 weeks ]
    fasting total cholesterol, LDL-c, HDL-c, triglycerides

  5. Changes from baseline in anthropometric measures [ Time Frame: 4, 8, 12, 24, 36, 48 weeks ]
    waist circumference, body weight and BMI

  6. Changes from baseline in liver-related inflammatory markers [ Time Frame: 4, 8, 12, 24, 36 weeks ]
    IL-6, IL-8, TNF-alpha, TGF-beta, C-reactive protein

  7. Changes in AFP levels from baseline [ Time Frame: 12, 24, 36, 48 weeks ]
    AFP

  8. Participant acceptability to study medication dosing (in Arm 1 only) [ Time Frame: 8, 24, 48 weeks ]
    Participant acceptability will be evaluated in Arm 1 only using the Treatment Satisfaction Questionnaire for Medication (TSQM), Version 1.4

  9. Changes from baseline in diet [ Time Frame: 24, 48 weeks ]
    Changes in diet from baseline will be captured using the International Physical Activity Questionnaire short-form (IPAQ-sf)

  10. Changes from baseline in physical exercise parameters [ Time Frame: 24, 48 weeks ]
    Changes in physical activity from baseline will be captured using the International Physical Activity Questionnaire short-form (IPAQ-sf)


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 79 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02306070


Locations
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Canada, Ontario
The Ottawa Hospital, General Campus
Ottawa, Ontario, Canada
Sponsors and Collaborators
Ottawa Hospital Research Institute
CIHR Canadian HIV Trials Network
Investigators
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Principal Investigator: Curtis Cooper, MD The Ottawa Hospital Division of Infectious Diseases
More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier: NCT02306070    
Other Study ID Numbers: CTNPT 019
First Posted: December 3, 2014    Key Record Dates
Last Update Posted: April 17, 2018
Last Verified: September 2017
Additional relevant MeSH terms:
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Metformin
Hepatitis C
Hepatitis
Liver Diseases
Digestive System Diseases
Blood-Borne Infections
Communicable Diseases
 Infections
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Hypoglycemic Agents
Physiological Effects of Drugs