Clinical trial NCT02929225: Effectiveness of Probiotics to Treat End Stage Renal Disease
Official title: Effect of Probiotics on Modulating the Bacterial Translocation and Improving Micro-inflammation in Hemodialysis Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Kidney Failure, Chronic
Keywords: bacterial translocation;micro-inflammation;hemodialysis
Lead sponsor: First Affiliated Hospital Xi'an Jiaotong University
Sponsor class: OTHER
First posted: 2016-10-11
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

* maintenance hemodialysis patients(MHP),dialysis age\>3 months;
* signed informed consent.

Exclusion Criteria:

* intolerance to whole milk and dairy products;
* patients with kidney transplant, with severe infections, sever heart disease and liver disease, malignancy, autoimmune disorders, severe malnutrition, or clinical conditions requiring artificial feeding;
* pregnant or nursing women;
* patients with known gastro-intestinal disease (i.e.,inflammatory bowel disease,crohn's disease,ulcerative colitis),receiving or have received radiation to the bowel or large bowel resection;
* use of antibiotics, prebiotics or probiotics in the past 4 weeks;

Primary outcomes:
measure: Gut microbiota
timeFrame: Change from Baseline in faeces bacterial genomic DNA at 6 months
Secondary outcomes:
measure: plasma detection of bacterial genomic DNA,plasma and fecal metabolomics
timeFrame: Change from Baseline in faeces bacterial genomic DNA at 6 months, fecal and plasma metabolomics at baseline and 6 months
measure: plasma concentrations of inflammatory biomarkers(hs-C reactive protein,Interleukin(IL)-6,tumor necrosis factor(TNF)-α,endotoxin)
timeFrame: baseline,3 months and 6 months
measure: Gastrointestinal Symptom Rating Scale (GSRS),SF-36
timeFrame: baseline，3 and 6 months
Other outcomes:
Locations:
city: Xi'an
country: China
facility: First Affiliated Hospital of Xi'an Jiaotong University
state: Shanxi
Study officials:
affiliation: First Affiliated Hospital Xi'an Jiaotong University
name: Hongli Jiang, professor
role: STUDY_CHAIR
References:
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