Metformin as Add-on to the Standard Therapy in Patients With Chronic Hepatitis B

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of metformin as add-on to entecavir therapy in patients with chronic hepatitis B.

Detailed Description
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This is a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of metformin as add-on to entecavir therapy in patients with chronic hepatitis B. Patients with chronic hepatitis B who met eligibility criteria were randomly assigned (1:1) to receive either metformin (1000 mg, oral, once a day) or placebo (oral, once a day) for 24 weeks in addition to their ongoing entecavir therapy. Patients and investigators were both blinded to group allocation. The primary outcome, serum HBsAg level (log IU/mL) at weeks 24 and 36, was analysed using a linear mixed-effect model. The intention-to-treat populations were included in primary and safety analyses.

Official Title
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Metformin as Add-on to the Standard Therapy in Patients With Chronic Hepatitis B: A Randomized, Double-Blind, Placebo-Controlled Trial

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: Metformin & Entecavir
* Drug: Placebo & Entecavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HBeAg-negative chronic hepatitis B Ongoing treatment with Entecavir for more than 12 months HBV DNA < 500 IU/mL Quantitative HBsAg < 3 log IU/mL ALT and AST < 2 × upper limit of normal (ULN) Agree to take contraceptive measures during participation for women of a fertile age Agree not to engage in other clinical trials during participation Understand and sign the informed consent form before taking any steps related to this study Exclusion Criteria: Diabetes mellitus Alcoholic liver disease Drug-induced liver damage Autoimmune liver disease Decompensated cirrhosis Liver cancer Liver transplantation Pregnant or lactating women Other conditions unsuitable for participation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combination Therapy<br>Metformin as add-on to entecavir therapy in patients with chronic hepatitis B | Drug: Metformin & Entecavir<br>* Adding sustained-release metformin hydrochloride (1000 mg, oral, once a day) for 24 weeks to the ongoing entecavir therapy (0.5 mg, oral, once a day)<br>* Other names: Combination Therapy;|
| Placebo Comparator: Standard Therapy<br>Entecavir monotherapy in patients with chronic hepatitis B | Drug: Placebo & Entecavir<br>* Adding placebo (oral, once a day) for 24 weeks to the ongoing entecavir therapy (0.5 mg, oral, once a day)<br>* Other names: Standard Therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum HBsAg level | log IU/mL | weeks 24 and 36 after adding metformin or a placebo | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| weight | kg | weeks 24 and 36 after adding metformin or a placebo | 
| body mass index | kg/m^2 | weeks 24 and 36 after adding metformin or a placebo | 
| fasting glucose | mmol/L | weeks 24 and 36 after adding metformin or a placebo | 
| HbA1c | percentage (%) | weeks 24 and 36 after adding metformin or a placebo | 
| triglycerides | mmol/L | weeks 24 and 36 after adding metformin or a placebo | 
| total cholesterol | mmol/L | weeks 24 and 36 after adding metformin or a placebo | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metformin, Entecavir, chronic hepatitis B, hepatitis B virus