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

Primary Purpose

Chronic Hepatitis B

Status
Completed
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Metformin & Entecavir
Placebo & Entecavir
Sponsored by
Fu-Sheng Wang
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis B focused on measuring Metformin, Entecavir, chronic hepatitis B, hepatitis B virus

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • The 960th Hospital of Chinese PLA Joint Logistics Support Force (Jinan Military General Hospital)

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Combination Therapy

Standard Therapy

Arm Description

Metformin as add-on to entecavir therapy in patients with chronic hepatitis B

Entecavir monotherapy in patients with chronic hepatitis B

Outcomes

Primary Outcome Measures

serum HBsAg level
log IU/mL

Secondary Outcome Measures

weight
kg
body mass index
kg/m^2
fasting glucose
mmol/L
HbA1c
percentage (%)
triglycerides
mmol/L
total cholesterol
mmol/L

Full Information

First Posted
November 27, 2019
Last Updated
November 23, 2021
Sponsor
Fu-Sheng Wang
Collaborators
Jinan Military General Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04182321
Brief Title
Metformin as Add-on to the Standard Therapy in Patients With Chronic Hepatitis B
Official Title
Metformin as Add-on to the Standard Therapy in Patients With Chronic Hepatitis B: A Randomized, Double-Blind, Placebo-Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
March 13, 2020 (Actual)
Primary Completion Date
July 2, 2021 (Actual)
Study Completion Date
September 13, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Fu-Sheng Wang
Collaborators
Jinan Military General Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis B
Keywords
Metformin, Entecavir, chronic hepatitis B, hepatitis B virus

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Combination Therapy
Arm Type
Experimental
Arm Description
Metformin as add-on to entecavir therapy in patients with chronic hepatitis B
Arm Title
Standard Therapy
Arm Type
Placebo Comparator
Arm Description
Entecavir monotherapy in patients with chronic hepatitis B
Intervention Type
Drug
Intervention Name(s)
Metformin & Entecavir
Other Intervention Name(s)
Combination Therapy
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Placebo & Entecavir
Other Intervention Name(s)
Standard Therapy
Intervention Description
Adding placebo (oral, once a day) for 24 weeks to the ongoing entecavir therapy (0.5 mg, oral, once a day)
Primary Outcome Measure Information:
Title
serum HBsAg level
Description
log IU/mL
Time Frame
weeks 24 and 36 after adding metformin or a placebo
Secondary Outcome Measure Information:
Title
weight
Description
kg
Time Frame
weeks 24 and 36 after adding metformin or a placebo
Title
body mass index
Description
kg/m^2
Time Frame
weeks 24 and 36 after adding metformin or a placebo
Title
fasting glucose
Description
mmol/L
Time Frame
weeks 24 and 36 after adding metformin or a placebo
Title
HbA1c
Description
percentage (%)
Time Frame
weeks 24 and 36 after adding metformin or a placebo
Title
triglycerides
Description
mmol/L
Time Frame
weeks 24 and 36 after adding metformin or a placebo
Title
total cholesterol
Description
mmol/L
Time Frame
weeks 24 and 36 after adding metformin or a placebo

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fu-Sheng Wang
Organizational Affiliation
The Fifth Medical Center of Chinese PLA General Hospital (Beijing 302 Hospital)
Official's Role
Study Chair
Facility Information:
Facility Name
The 960th Hospital of Chinese PLA Joint Logistics Support Force (Jinan Military General Hospital)
City
Tai'an
State/Province
Shandong
ZIP/Postal Code
271000
Country
China

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Deidentified individual participant data and full study protocol are available upon reasonable request. Researchers should send it to fswang302@163.com to gain access.
IPD Sharing Time Frame
After publication of the study results
IPD Sharing Access Criteria
Researchers interested in our study
Citations:
PubMed Identifier
29599078
Citation
Polaris Observatory Collaborators. Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study. Lancet Gastroenterol Hepatol. 2018 Jun;3(6):383-403. doi: 10.1016/S2468-1253(18)30056-6. Epub 2018 Mar 27.
Results Reference
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PubMed Identifier
30496103
Citation
GBD 2017 Causes of Death Collaborators. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018 Nov 10;392(10159):1736-1788. doi: 10.1016/S0140-6736(18)32203-7. Epub 2018 Nov 8. Erratum In: Lancet. 2019 Jun 22;393(10190):e44. Lancet. 2018 Nov 17;392(10160):2170.
Results Reference
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PubMed Identifier
26563120
Citation
Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, Chen DS, Chen HL, Chen PJ, Chien RN, Dokmeci AK, Gane E, Hou JL, Jafri W, Jia J, Kim JH, Lai CL, Lee HC, Lim SG, Liu CJ, Locarnini S, Al Mahtab M, Mohamed R, Omata M, Park J, Piratvisuth T, Sharma BC, Sollano J, Wang FS, Wei L, Yuen MF, Zheng SS, Kao JH. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016 Jan;10(1):1-98. doi: 10.1007/s12072-015-9675-4. Epub 2015 Nov 13.
Results Reference
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PubMed Identifier
28427875
Citation
European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017 Aug;67(2):370-398. doi: 10.1016/j.jhep.2017.03.021. Epub 2017 Apr 18.
Results Reference
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PubMed Identifier
29405329
Citation
Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, Brown RS Jr, Bzowej NH, Wong JB. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018 Apr;67(4):1560-1599. doi: 10.1002/hep.29800. No abstract available.
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PubMed Identifier
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Citation
Xun YH, Zhang YJ, Pan QC, Mao RC, Qin YL, Liu HY, Zhang YM, Yu YS, Tang ZH, Lu MJ, Zang GQ, Zhang JM. Metformin inhibits hepatitis B virus protein production and replication in human hepatoma cells. J Viral Hepat. 2014 Aug;21(8):597-603. doi: 10.1111/jvh.12187. Epub 2013 Oct 24.
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Citation
Honda M, Shirasaki T, Terashima T, Kawaguchi K, Nakamura M, Oishi N, Wang X, Shimakami T, Okada H, Arai K, Yamashita T, Sakai Y, Yamashita T, Mizukoshi E, Kaneko S. Hepatitis B Virus (HBV) Core-Related Antigen During Nucleos(t)ide Analog Therapy Is Related to Intra-hepatic HBV Replication and Development of Hepatocellular Carcinoma. J Infect Dis. 2016 Apr 1;213(7):1096-106. doi: 10.1093/infdis/jiv572. Epub 2015 Nov 29.
Results Reference
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Metformin as Add-on to the Standard Therapy in Patients With Chronic Hepatitis B

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