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

NCT ID: NCT04182321

Last Updated: 2021-12-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-03-13

Study Completion Date

2021-09-13

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.

Conditions

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Chronic Hepatitis B

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Combination Therapy

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

Group Type EXPERIMENTAL

Metformin & Entecavir

Intervention Type DRUG

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)

Standard Therapy

Entecavir monotherapy in patients with chronic hepatitis B

Group Type PLACEBO_COMPARATOR

Placebo & Entecavir

Intervention Type DRUG

Adding placebo (oral, once a day) for 24 weeks to the ongoing entecavir therapy (0.5 mg, oral, once a day)

Interventions

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Metformin & Entecavir

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

Placebo & Entecavir

Adding placebo (oral, once a day) for 24 weeks to the ongoing entecavir therapy (0.5 mg, oral, once a day)

Intervention Type DRUG

Other Intervention Names

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Combination Therapy Standard Therapy

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Jinan Military General Hospital

OTHER

Sponsor Role collaborator

Fu-Sheng Wang

OTHER

Sponsor Role lead

Responsible Party

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Fu-Sheng Wang

Study Chair

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Fu-Sheng Wang

Role: STUDY_CHAIR

The Fifth Medical Center of Chinese PLA General Hospital (Beijing 302 Hospital)

Locations

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

Tai’an, Shandong, China

Site Status

Countries

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China

References

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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.

Reference Type BACKGROUND
PMID: 29599078 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30496103 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26563120 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28427875 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29405329 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24164660 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26621908 (View on PubMed)

Other Identifiers

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960-2019-84

Identifier Type: -

Identifier Source: org_study_id

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