The Curative Effect of Entecavir Combined Resveratrol on HBV patients-a Multi-center, Random, Open Clinical Trial
Primary Purpose
Hepatitis
Status
Completed
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
entecavir+resveratrol
Entecavir
entecavir+thymosin α1
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis focused on measuring entecavir, resveratrol, thymosin, hepatitis B
Eligibility Criteria
Inclusion Criteria:
- Serologic evidence of chronic hepatitis B infection more than 6 months- HBeAg positive and HBeAb negative;
- HBV DNA≥20000 IU/ml (equals to 105 copy/ml);
- 2×ULN ≤ALT≤10×ULN,TBIL<2×ULN
Exclusion Criteria:
- Has history of decompensated liver diseases
- Has been treated with other anti-virus drugs, or anti-tumor drugs, immuno-suppression drugs
- Has a history of autoimmune hepatitis
- History of a severe seizure disorder or current anticonvulsant use
- History or other evidence of a medical condition associated with chronic liver disease other than HBV which would make the patient, in the opinion of the investigator, unsuitable for the study (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures)
- History of thyroid disease poorly controlled on prescribed medications, elevated thyroid stimulating hormone (TSH) concentrations with elevation of antibodies to thyroid peroxidase and any clinical manifestations of thyroid disease
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
entecavir
entecavir+resveratrol
entecavir+thymosin α1
Arm Description
drug:entecavir 0.5mg/day, one time/day,144weeks
entecavir 0.5mg/day, 144weeks intervention:resveratrol 1000mg/day, 48weeks
entecavir 0.5mg/day, 144weeks thymosin α1 2 times/week, 24weeks
Outcomes
Primary Outcome Measures
HBeAg seroconversion rate
HBeAg seroconversion rate
Secondary Outcome Measures
HBsAg loss rate, decline and seroconversion rate
HBsAg loss rate, decline and seroconversion rate
HBeAg seroconversion rate and loss rate
HBeAg seroconversion rate and loss rate
cccDNA decline level
cccDNA decline level
Full Information
NCT ID
NCT03509688
First Posted
May 2, 2017
Last Updated
April 25, 2018
Sponsor
The First Hospital of Jilin University
Collaborators
Chinese Academy of Sciences
1. Study Identification
Unique Protocol Identification Number
NCT03509688
Brief Title
The Curative Effect of Entecavir Combined Resveratrol on HBV patients-a Multi-center, Random, Open Clinical Trial
Official Title
The Curative Effect and Security of Entecavir Combined Thymosin or Resveratrol on HBeAg Positive Chronic Hepatitis B Patients - a Multi-center, Random, Control, Open Clinical Trial
Study Type
Interventional
2. Study Status
Record Verification Date
April 2018
Overall Recruitment Status
Completed
Study Start Date
November 2014 (Actual)
Primary Completion Date
December 2017 (Actual)
Study Completion Date
December 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The First Hospital of Jilin University
Collaborators
Chinese Academy of Sciences
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
The purpose of this study is to use entecavir combined with other drug such as resveratrol and thymosin to treat patients with hepatitis B, which may provide a novel therapy target hepatitis B.
Detailed Description
Hepatitis B virus (HBV) infections continue to be a major public health problem worldwide. More than 400 million people worldwide are currently infected with hepatitis B virus. Approximately 20% of HBV patients will develop chronic hepatitis, and are at significant risk of developing cirrhosis or liver hepatocarcinoma. HBV is the prototype of hepadnaviridae, a family of small enveloped hepatotropic DNA viruses that can infect the liver of human.
In recent years, researches on antiviral treatment of chronic hepatitis B has made remarkable progress, interferon and nucleoside analogues which are the synthetic reverse transcriptase inhibitors can attenuate liver inflammation and fibrosis. However, HBsAg and HBeAg seroconversion ratio is merely 7% and 21%, respectively. To completely clear HBsAg is very difficult, the main reason is that HBV cccDNA (a covalently closed circular form of the viral genome through DNA repair of the relaxed circular replicative HBV DNA inside the nuclei of hepatocytes in the HBV life cycle), the template for viral and pregenomic messenger RNA cannot be eliminated, lead to the continuous replication of the virus. Apart from that, none of these therapies are completely safe and effective. Although direct antiviral therapy could efficiently control chronic active hepatitis B, drug resistance or renal toxicity could develop progressively several months after the initiation of therapy. It is thus still urgently required to identify effective anti-HBV agents.
Pegylated IFN-α (pegIFN-α) is effective in achieving sustained virologic response, defined as HBeAg seroconversion and/or hepatitis B virus (HBV) DNA levels below 20,000 copies/mL at 6 months after completion of the therapy, in only 30% of hepatitis e antigen (HBeAg)-positive and 40% of HBeAg-negative cases. However, the pegIFN-α therapy does promote HBsAg clearance or seroconversion in a small, but significant fraction of treated patients. Hence, we should develop feasible antiviral therapeutics target cccDNA in liver cells to cure chronic hepatitis B.
Resveratrol, a grape polyphenol, is representative of a group of diet-derived putative cancer chemopreventive agents encompassing, among others, curcumin, tea polyphenols and apigenin, which have attracted a lot of interest in the cancer chemoprevention community. It has shown considerable promise as a therapeutic agent in the treatment of liver ailments. Recent study found that SITR1 activators can inhibit cccDNA, and resceratrol is a member of SIRT1 activator family. Apart from that, several studies have highlighted the hepatoprotective properties of resveratrol. Resveratrol has been shown to prevent hepatic damage because of free radicals and inflammatory cytokines, induce antioxidant enzymes and elevate glutathione content. Resveratrol has also been shown to modulate varied signal transduction pathways implicated in liver diseases. For instance, resveratrol can inhibit Th17 proliferation and function, and many researches found that increasing Th17 in patients with hepatitis B. Importantly, in vitro, we found that resveratrol can significantly reduce both HBsAg and HBeAg in a dose-depend manner.
Nowadays, increasing studies focus on natural materials in the application of the treatment, and there are many health care products used resveratrol as main ingredient. Report on trial of resveratrol in healthy volunteers after daily doses of up to 5g per day administered for 29 days suggests that it is safe, as borne out by the lack of serious adverse reactions detected by clinical, biochemical or hematological analyses during the study and study follow-up. Besides, in our country, the traditional Chinese medicine also used giant knotweed (main ingredients is resveratrol) to treat viral hepatitis and autoimmune hepatitis.
Therefore, We aim to use entecavir combined with other drug such as resveratrol and peg-interferon to treat patients with hepatitis B, which may provide a novel therapy target hepatitis B.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis
Keywords
entecavir, resveratrol, thymosin, hepatitis B
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
312 (Actual)
8. Arms, Groups, and Interventions
Arm Title
entecavir
Arm Type
Experimental
Arm Description
drug:entecavir 0.5mg/day, one time/day,144weeks
Arm Title
entecavir+resveratrol
Arm Type
Experimental
Arm Description
entecavir 0.5mg/day, 144weeks intervention:resveratrol 1000mg/day, 48weeks
Arm Title
entecavir+thymosin α1
Arm Type
Experimental
Arm Description
entecavir 0.5mg/day, 144weeks thymosin α1 2 times/week, 24weeks
Intervention Type
Drug
Intervention Name(s)
entecavir+resveratrol
Intervention Description
entecavir+resveratrol
Intervention Type
Drug
Intervention Name(s)
Entecavir
Intervention Description
Entecavir
Intervention Type
Drug
Intervention Name(s)
entecavir+thymosin α1
Intervention Description
entecavir+thymosin α1
Primary Outcome Measure Information:
Title
HBeAg seroconversion rate
Description
HBeAg seroconversion rate
Time Frame
48 weeks
Secondary Outcome Measure Information:
Title
HBsAg loss rate, decline and seroconversion rate
Description
HBsAg loss rate, decline and seroconversion rate
Time Frame
48 weeks
Title
HBeAg seroconversion rate and loss rate
Description
HBeAg seroconversion rate and loss rate
Time Frame
72 weeks
Title
cccDNA decline level
Description
cccDNA decline level
Time Frame
48 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Serologic evidence of chronic hepatitis B infection more than 6 months- HBeAg positive and HBeAb negative;
HBV DNA≥20000 IU/ml (equals to 105 copy/ml);
2×ULN ≤ALT≤10×ULN,TBIL<2×ULN
Exclusion Criteria:
Has history of decompensated liver diseases
Has been treated with other anti-virus drugs, or anti-tumor drugs, immuno-suppression drugs
Has a history of autoimmune hepatitis
History of a severe seizure disorder or current anticonvulsant use
History or other evidence of a medical condition associated with chronic liver disease other than HBV which would make the patient, in the opinion of the investigator, unsuitable for the study (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures)
History of thyroid disease poorly controlled on prescribed medications, elevated thyroid stimulating hormone (TSH) concentrations with elevation of antibodies to thyroid peroxidase and any clinical manifestations of thyroid disease
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Junqi Niu, PHD
Organizational Affiliation
The First Hospital of Jilin University
Official's Role
Study Chair
12. IPD Sharing Statement
Learn more about this trial
The Curative Effect of Entecavir Combined Resveratrol on HBV patients-a Multi-center, Random, Open Clinical Trial
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