Clinical trial NCT03429439: Study on Effect of Intestinal Microbiota Transplantation in Chronic Hepatitis B
Official title: A Randomised Study on Intestinal Microbiota Transplantation for Chronic Hepatitis B Combined With Antiviral Therapy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Chronic Hepatitis b
Keywords: chronic hepatitis B
intestinal microbiota transplantation
microbiota
antiviral therapy
Lead sponsor: Zhongshan Hospital Xiamen University
Sponsor class: OTHER
First posted: 2018-02-12
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: an open label, parallel study
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Written informed consent/assent as appropriate
* 18 to 65 years of age
* No alcohol consumption or alcohol consumption \<140g per week in men, and \<70g per ween in women
* Been diagnosed with chronic hepatitis B

Exclusion Criteria:

* Alcoholic liver disease (ALD), chronic hepatitis C, autoimmune liver disease, Wilson's disease
* Drug treatment (tamoxifen, amiodarone, sodium valproate, methotrexate, glucocorticoids, etc.), total parenteral nutrition, inflammatory bowel disease, hypothyroidism, Cushing's syndrome, beta lipoprotein deficiency, insulin resistance related syndromes (lipid wasting diabetes mellitus, Mauriac syndrome), gastrointestinal surgery
* Hepatocellular carcinoma (HCC), biliary tract diseases and taking or taking chinese and western medicines that can lead liver enzymes elevation in the near future.
* Moderate and severe renal injury(serum creatinine\>2mg/dL or 177mmol/L), moderate and severe chronic obstructive pulmonary disease, severe hypertension, cerebrovascular accident, congestive heart failure, unstable angina pectoris.
* Antibiotics treatment in 7 days before recruited and unwilling to stop it, long-term lipid-lowering drugs, antidiabetic drugs and other liver protecting drugs treatment
* Antibiotics, other probiotics, gastrointestinal motility drugs and other preparation that may influence intestinal microbiota treatment
* Other serious diseases that may interfere the recruitment or affect the survival, such as cancer or acquired immune deficiency syndrome
* Mentally or legally disabled person
* Preparing for pregnancy
* Medical or social condition which in the opinion of the principal investigator would interfere with or prevent regular follow up
* Participating in other clinical trials.

Primary outcomes:
measure: Change of serum hepatitis B virus e antigen(HBeAg) level
timeFrame: 1 month, 3 months, 6months
Secondary outcomes:
measure: Change of serum hepatitis B virus surface antigen(HBsAg) level
timeFrame: 1 month, 3 months, 6months
measure: Change of serum anti-hepatitis B virus e antigen(anti-HBe)
timeFrame: 1 month, 3 months, 6months
measure: Change of serum anti-hepatitis B virus surface antigen(anti-HBs)
timeFrame: 1 month, 3 months, 6months
measure: Changes of gut microbiota
timeFrame: 1 month, 3 months, 6months
measure: relief of constipation
timeFrame: 1 month, 3 months, 6months
measure: relief of diarrhea
timeFrame: 1 month, 3 months, 6months
measure: relief of abdominal pain
timeFrame: 1 month, 3 months, 6months
Other outcomes:
Locations:
city: Xiamen
country: China
facility: Zhongshan Hospital Affiliated to Xiamen University
state: Fujian
Study officials:
References: