Clinical trial NCT04182321: 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
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Hepatitis B
Keywords: Metformin
Entecavir
chronic hepatitis B
hepatitis B virus
Lead sponsor: Beijing 302 Hospital
Sponsor class: OTHER
Collaborators: name: Jinan Military General Hospital
First posted: 2019-12-02
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: serum HBsAg level
timeFrame: weeks 24 and 36 after adding metformin or a placebo
Secondary outcomes:
measure: weight
timeFrame: weeks 24 and 36 after adding metformin or a placebo
measure: body mass index
timeFrame: weeks 24 and 36 after adding metformin or a placebo
measure: fasting glucose
timeFrame: weeks 24 and 36 after adding metformin or a placebo
measure: HbA1c
timeFrame: weeks 24 and 36 after adding metformin or a placebo
measure: triglycerides
timeFrame: weeks 24 and 36 after adding metformin or a placebo
measure: total cholesterol
timeFrame: weeks 24 and 36 after adding metformin or a placebo
Other outcomes:
Locations:
city: Tai'an
country: China
facility: The 960th Hospital of Chinese PLA Joint Logistics Support Force (Jinan Military General Hospital)
state: Shandong
Study officials:
affiliation: The Fifth Medical Center of Chinese PLA General Hospital (Beijing 302 Hospital)
name: Fu-Sheng Wang
role: STUDY_CHAIR
References:
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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.
citation: 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.
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.
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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