NCT04182321

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
60

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Mar 2020

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 27, 2019

Completed
5 days until next milestone

First Posted

Study publicly available on registry

December 2, 2019

Completed
3 months until next milestone

Study Start

First participant enrolled

March 13, 2020

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 2, 2021

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 13, 2021

Completed
Last Updated

December 7, 2021

Status Verified

November 1, 2021

Enrollment Period

1.3 years

First QC Date

November 27, 2019

Last Update Submit

November 23, 2021

Conditions

Chronic Hepatitis B

Keywords

MetforminEntecavirchronic hepatitis Bhepatitis B virus

Outcome Measures

Primary Outcomes (1)

  • serum HBsAg level

    log IU/mL

    weeks 24 and 36 after adding metformin or a placebo

Secondary Outcomes (6)

  • weight

    weeks 24 and 36 after adding metformin or a placebo

  • body mass index

    weeks 24 and 36 after adding metformin or a placebo

  • fasting glucose

    weeks 24 and 36 after adding metformin or a placebo

  • HbA1c

    weeks 24 and 36 after adding metformin or a placebo

  • triglycerides

    weeks 24 and 36 after adding metformin or a placebo

  • +1 more secondary outcomes

Study Arms (2)

Combination Therapy

EXPERIMENTAL

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

Drug: Metformin & Entecavir

Standard Therapy

PLACEBO COMPARATOR

Entecavir monotherapy in patients with chronic hepatitis B

Drug: Placebo & Entecavir

Interventions

Metformin & EntecavirDRUG

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)

Also known as: Combination Therapy
Combination Therapy
Placebo & EntecavirDRUG

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

Also known as: Standard Therapy
Standard Therapy

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

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

Tai’an, Shandong, 271000, China

Location

Related Publications (7)

  • 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.

    PMID: 29599078BACKGROUND

  • 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.

    PMID: 30496103BACKGROUND

  • 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.

    PMID: 26563120BACKGROUND

  • 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.

    PMID: 28427875BACKGROUND

  • 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.

    PMID: 29405329BACKGROUND

  • 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.

    PMID: 24164660BACKGROUND

  • 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.

    PMID: 26621908BACKGROUND

MeSH Terms

Conditions

Hepatitis B, ChronicHepatitis B

Interventions

MetforminentecavirCombined Modality TherapyStandard of Care

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsHepadnaviridae InfectionsDNA Virus InfectionsVirus DiseasesHepatitis, Viral, HumanHepatitis, ChronicHepatitisLiver DiseasesDigestive System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

BiguanidesGuanidinesAmidinesOrganic ChemicalsTherapeuticsQuality Indicators, Health CareQuality of Health CareHealth Services AdministrationHealth Care Quality, Access, and Evaluation

Study Officials

  • Fu-Sheng Wang

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

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Study Chair

Study Record Dates

First Submitted

November 27, 2019

First Posted

December 2, 2019

Study Start

March 13, 2020

Primary Completion

July 2, 2021

Study Completion

September 13, 2021

Last Updated

December 7, 2021

Record last verified: 2021-11

Data Sharing

IPD Sharing
Will share

Deidentified individual participant data and full study protocol are available upon reasonable request. Researchers should send it to fswang302@163.com to gain access.

Shared Documents
STUDY PROTOCOL
Time Frame
After publication of the study results
Access Criteria
Researchers interested in our study

Locations

CN(1)