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

Chronic Hepatitis B Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04182321
• Other study ID #: 960-2019-84
• Status: Completed
• Phase: N/A
• Start date: March 13, 2020
• Est. completion date: September 13, 2021

Study information

• Verified date: November 2021
• Source: Beijing 302 Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: September 13, 2021
• Est. primary completion date: July 2, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• 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)
• Placebo & Entecavir
Adding placebo (oral, once a day) for 24 weeks to the ongoing entecavir therapy (0.5 mg, oral, once a day)

Locations

Country	Name	City	State
China	The 960th Hospital of Chinese PLA Joint Logistics Support Force (Jinan Military General Hospital)	Tai'an	Shandong

Sponsors (2)

Lead Sponsor	Collaborator
Fu-Sheng Wang	Jinan Military General Hospital

Country where clinical trial is conducted

China, 

References & Publications (7)

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. — View 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. — View 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. — View 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. Review. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	serum HBsAg level	log IU/mL	weeks 24 and 36 after adding metformin or a placebo
Secondary	weight	kg	weeks 24 and 36 after adding metformin or a placebo
Secondary	body mass index	kg/m^2	weeks 24 and 36 after adding metformin or a placebo
Secondary	fasting glucose	mmol/L	weeks 24 and 36 after adding metformin or a placebo
Secondary	HbA1c	percentage (%)	weeks 24 and 36 after adding metformin or a placebo
Secondary	triglycerides	mmol/L	weeks 24 and 36 after adding metformin or a placebo
Secondary	total cholesterol	mmol/L	weeks 24 and 36 after adding metformin or a placebo