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Chronic hepatitis B(CHB) is a common infectious disease affecting up to 2 billion people worldwide. Around 650 thousand people died of liver failure, cirrhosis and primary liver cancer caused by chronic hepatitis B every year. Age is the main factor affecting the chronicity of hepatitis B, while 90% and 25% to 30% of hepatitis b virus(HBV) infection in perinatal and infant period will develop into chronic infection respectively. Whereas the proportion in patients above 5 years old is only 5% to 10%. Intestinal microbiota plays an important role in maintaining normal physiological function of the intestine and the immune function of the body. It has been found that the disorder of intestinal microbiota is associated with numerous intestinal and parenteral diseases. Intestinal microbiota transplantation(IMT) is a significant method to reconstruct intestinal flora. Recently, the relationship between immune response and intestinal microbiota has been claimed. In a previous study using IMT to treat HBeAg positive chronic hepatitis B patients combined with antiviral therapy, 80% of them has reached HBeAg clearance. The investigators propose a randomised trial of IMT in patients with chronic hepatitis B combined with antiviral therapy. The investigators will assess the serum HBsAg, anti-HBs, HBeAg, anti-HBe, anti-hepatitis B core antigen, the relief of gastrointestinal symptoms, and the fecal microbiota before and after IMT. Patients will be randomized to either antiviral therapy or IMT combined antiviral therapy over a 26 weeks period.
A group of 60 chronic hepatitis B patients combined with antiviral therapy will be recruited for study, which involved a 6 times IMT with gastroduodenoscopy and the time interval is generally 2 weeks. All participants will keep their present antiviral therapy. All participants will be assessed at baseline, after 1 months, 3 months, 6 months from baseline in order to evaluate the possible changes in:(1)Decrease of serum hepatitis B virus surface antigen(HBsAg) levels(as measured in IU/mL) and hepatitis B virus e antigen(HBeAg) levels(as measured in S/CO); (2)Appearance of serum anti-hepatitis B virus surface antigen(anti-HBs) and anti-hepatitis B virus e antigen(anti-HBe); (3)Relief of gastrointestinal symptoms:The onset and duration of gastrointestinal symptoms will be assessed by "Evaluation Score Table of Gastrointestinal Symptoms"; (4)Changes of gut microbiota: The changes of gut microbiota will be assessed by High-throughput sequencing (16S rRNA) in fecal samples from recruited patients before and after IMT.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| IMT Combined with Antiviral Therapy | Experimental | 60 chronic hepatitis B patients ongoing antiviral therapy will be recruited for the study, which involved a 6 times intestinal microbiota transplant and the time interval is generally 2 weeks. Interventions: Procedure: Intestinal Microbiota Transplantation Procedure: antiviral therapy |
|
| Antiviral Agents | Other | 60 chronic hepatitis B patients ongoing antiviral therapy will be recruited for the study, which involved 12 months antiviral therapy. Interventions: Procedure: antiviral therapy |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| intestinal microbiota transplant | Other | Participants in experimental group take 6 times IMT with 2-week intervals. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change of serum hepatitis B virus e antigen(HBeAg) level | Serum hepatitis B virus e antigen(HBeAg) levels is measured in S/CO | 1 month, 3 months, 6months |
| Measure | Description | Time Frame |
|---|---|---|
| Change of serum hepatitis B virus surface antigen(HBsAg) level | Serum hepatitis B virus surface antigen(HBsAg) levels is measured in IU/mL . | 1 month, 3 months, 6months |
| Change of serum anti-hepatitis B virus e antigen(anti-HBe) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Fei Zhou | Contact | +8615396227038 | feiflyfei888@163.com | |
| Yurou Xie | Contact | +8618559620899 | 350951378@qq.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Zhongshan Hospital Affiliated to Xiamen University | Recruiting | Xiamen | Fujian | 361000 | China |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 28, 2017 | Feb 5, 2018 | Prot_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jun 28, 2017 | Feb 5, 2018 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D019694 | Hepatitis B, Chronic |
| ID | Term |
|---|---|
| D006509 | Hepatitis B |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D000069467 | Fecal Microbiota Transplantation |
| D000998 | Antiviral Agents |
| ID | Term |
|---|---|
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D000890 | Anti-Infective Agents |
| D045506 | Therapeutic Uses |
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an open label, parallel study
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| Antiviral Agents | Drug | All participants continue present antiviral therapy over 12 months. |
|
Appearance of serum anti-hepatitis B virus e antigen(anti-HBe) suggest the ability of body to resistant HBV.
| 1 month, 3 months, 6months |
| Change of serum anti-hepatitis B virus surface antigen(anti-HBs) | Appearance of serum anti-hepatitis B virus surface antigen(anti-HBs) suggest the ability of body to resistant HBV. | 1 month, 3 months, 6months |
| Changes of gut microbiota | Alpha and Beta diversity of GI microbiota by High-throughput sequencing (16S rRNA) on baseline line and1 month, 3 months, 6months after treatment | 1 month, 3 months, 6months |
| relief of constipation | The onset and duration of constipation will be assessed by "Evaluation Score Table of Gastrointestinal Symptoms". | 1 month, 3 months, 6months |
| relief of diarrhea | The onset and duration of diarrhea will be assessed by "Evaluation Score Table of Gastrointestinal Symptoms". | 1 month, 3 months, 6months |
| relief of abdominal pain | The onset and duration of abdominal pain will be assessed by "Evaluation Score Table of Gastrointestinal Symptoms". | 1 month, 3 months, 6months |
| D018347 |
| Hepadnaviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D006525 | Hepatitis, Viral, Human |
| D006521 | Hepatitis, Chronic |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D020228 |
| Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |