Effectiveness of Probiotics to Treat End Stage Renal Disease
Condition: Kidney Failure, Chronic
MeSH terms: Renal Insufficiency; Kidney Failure, Chronic
Study type: Interventional
Phase: Early Phase 1

Summary: 
      Intestinal microbiota has recently emerged as an important player in the progression and
      complications of chronic kidney disease(CKD). And drug therapy which selects the gut as a
      target has raised lots of concern. It has been reported that the composition of intestinal
      flora has changed in uremic patients. Specifically, imbalanced ecosystem has higher number of
      pathogens such as Clostridia, Enterobacteria,and lower number of beneficial microbes such as
      Lactobacilli and Bifidobacteria. This modification of intestinal flora can strongly increase
      transformation of amino acids into Uremic Retention solutes, e.g., indoxyl-sulfate (IS),
      p-cresyl sulfate (PCS), which are so called gut-derived uremic toxins. The dysbiosis also
      contributes to an increase in intestinal permeability by disrupting the colonic epithelial
      tight junction,which may subsequently lead to translocation of endotoxin and bacteria into
      the host's internal environment,resulting in systemic micro-inflammation.Also all of these
      can promote the progression of renal failure and the incidence of cardiovascular
      complications,renal osteodystrophy and anemia.Probiotics is defined by the World Health
      Organization as 'live microorganisms that, when administered in adequate amounts, confer a
      health benefit on the host'. Probiotics are being increasingly used for various pathologic
      conditions.It is said that probiotics have a therapeutic role in maintaining a metabolically
      balanced gastrointestinal tract (GIT).And in our previous study,the investigators found that
      in uremic rats,lactobacillus acidophilus can relieve bacterial translocation and decrease the
      level of inflammatory markers.So our study is mainly designed to investigate whether
      probiotics can modulate the balance of intestinal ecosystem, prevent the bacterial
      translocation from gut and alleviate the systemic inflammation in hemodialysis(HD) patients.
    

Detailed description: 
      This study is a single-centre, double-blind, placebo-controlled, randomised trial.
      Participants will undergo a 2 week run-in period, followed by randomisation to either
      probiotics supplements or placebo for 6 months. The study population are hemodialysis
      patients from Dialysis Department in First Affiliated Hospital of Xi'an Jiaotong University.
      The Dialysis Department have 400 patients who regularly come to receive dialysis therapy
      three times a week.It's relatively easy for us to follow up and collect data.Patients who
      meet the criteria and are able to provide informed consent will be recruited.Then
      computer-generated randomisation of participants to treatment order will be undertaken by an
      external statistical consultant. This process of allocation will conceal the randomisation
      order to researchers and participants. In addition, the supplements will be packed off-site
      with a generic label.

      After randomization,baseline data will be collected and all participants will undergo
      face-to-face dietary education with a dietitian, incorporating standard hemodialysis
      education during the first week of run-in.In the week following, and throughout the
      intervention, patients will be encouraged to maintain stable protein and fibre intakes, with
      specific attention to maintaining the same sources of these nutrients.Participants' dietary
      intakes during the study will be assessed every month using a semi-quantitative food
      frequency questionnaire. And when the trial starts, questionnaires and biological samples
      will be performed and collected at the corresponding time. All serious adverse events will be
      reported to the ethics committee, whether deemed to be intervention related or not. Adherence
      to supplements will be measured by pill count every two weeks.

      This study is an explorative clinical trial.And in the absence of any data about the effect
      of probiotics on hemodialysis patients intestinal and serum microbiota,sample size can't be
      calculated.Data will be reported as s mean±SD if normally distributed and as median(25-75%
      percentiles) if not. The Shapiro-Wilk test is performed to assess whether data are normally
      distributed. Statistical comparisons of normally distributed data are performed using
      Student's t-test. Mann-Whitney U-test is used to compare the rank variables measuring
      gastrointestinal symptoms in probiotics and placebo groups. The threshold for statistical
      significance is at p values <0.05. And an external statistical consultant from our Clinical
      Research Center will be involved in the data validation and analysis activities.
    

Intervention name(s): Bifid Triple Viable Capsules; placebo
Intervention type(s): Drug; Other
Intervention description(s): BIFICO is prescribed as a dose of 4 capsules twice daily in half hours after meals.; placebo is also prescribed as a dose of 4 capsules twice daily
Other intervention name(s): BIFICO,S10950032; placebo(Shanghai Sine Pharmaceutical Laboratories Co.Ltd)
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: bacterial translocation;micro-inflammation;hemodialysis