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The Curative Effect and Security of Interferon Combined Resveratrol on HBeAg Positive Chronic Hepatitis B Patients

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ClinicalTrials.gov Identifier: NCT03546530
Recruitment Status : Completed
First Posted : June 5, 2018
Last Update Posted : June 5, 2018
Sponsor:
Information provided by (Responsible Party):
First Hospital of Jilin University

Brief Summary:
The purpose of this study is to use Interferon Combined Resveratrol to treat patients with hepatitis B, which may provide a novel therapy target hepatitis B.

Condition or disease Intervention/treatment Phase
Hepatitis B Drug: Interferon Drug: Interferon+resveratrol Not Applicable

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 228 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Curative Effect and Security of Interferon Combined Resveratrol on HBeAg Positive Chronic Hepatitis B Patients - a Multi-center, Random, Control, Open Clinical Trial.
Actual Study Start Date : June 1, 2016
Actual Primary Completion Date : January 2017
Actual Study Completion Date : January 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Interferon
Interferon 1.5ug/kg/week, 48weeks
Drug: Interferon
Interferon

Experimental: Interferon+resveratrol
Interferon 1.5ug/kg/week,resveratrol 1000mg/day, 48weeks
Drug: Interferon+resveratrol
Interferon+resveratrol




Primary Outcome Measures :
  1. HBeAg seroconversion rate [ Time Frame: 48week ]
    HBeAg seroconversion rate



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03546530


Sponsors and Collaborators
First Hospital of Jilin University
Investigators
Principal Investigator: Junqi Niu, PHD First Hospital of Jilin University

Responsible Party: First Hospital of Jilin University
ClinicalTrials.gov Identifier: NCT03546530     History of Changes
Other Study ID Numbers: 2014ZX10002002
First Posted: June 5, 2018    Key Record Dates
Last Update Posted: June 5, 2018
Last Verified: May 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis B
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Resveratrol
Interferons
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Antioxidants
Molecular Mechanisms of Pharmacological Action