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Beneficial Effect of Probiotics on Chronic Kidney Disease

Beneficial Effect of Probiotics on Chronic Kidney Disease

Status
Completed
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01391468
Enrollment
47
Registered
2011-07-12
Start date
2011-08-31
Completion date
2013-12-31
Last updated
2015-11-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Kidney Disease

Brief summary

This is a randomized double blinded placebo control studies are performed in Chronic Kidney Disease (CKD) patients. After informed consent, intervention group receives probiotics containing 109 CFU B. bifidum, B.catenulatum, B. longum, and L.plantarm), while placebo group receives corn starch. In the first year the investigators examine the 60 peritoneal dialysis (PD) patients, in the second year the investigators do the 60 hemodialysis (HD) patients, and in the third year the investigators do the 60 stage 3 and 4 CKD patients. Primary endpoint is cardiovascular event, gastrointestinal symptoms, peritonitis in PD patients, and progression of stage 3 and 4 CKD. Values are compared between the groups by unpaired t test. X2 testis used to compare proportions between the groups. Relative risk and the number needed to treat, both with 95% CI, are used to describe the treatment effect of probiotics. A p value less than 0•05 is regarded as statistically significant.

Detailed description

Chronic kidney disease (CKD) is a global health issue that has a substantial impact on affected individuals. The prognosis of dialysis patients is poor with 30 to 50 percent 5 year survival in nondiabetic patients and 25 percent in diabetics. Cardiovascular disease accounts for approximately half of death of dialysis patients Chronic inflammation, which is widely seen in long-term dialysis patients, is associated with malnutrition, atherosclerosis and an increased mortality risk. Inflammatory markers such as C-reactive protein (CRP),IL-6, Il-18 and TNF-α, are elevated in dialysis and can predict cardiovascular event and all-cause mortality. Probiotics are microorganisms that have beneficial properties for the host. Three described benefits include suppression of growth or epithelial binding/invasion by pathogenic bacteria, improvement of intestinal barrier function and modulation the immune systems. Several probiotics preparations induce protective cytokines, including IL-10, and suppress proinflammatory cytokines, such as TNF-α and IL-6. Intestinal microflora is deranged in hemodialysis (HD) patients as an increase in aerobic bacteria such as E. coli and a decrease in anaerobic bacteria such as Bifidobacterium. One study reported that oral administration of ifidobacterium longum in a gastroresistant seamless capsule decreases the the pre-HD serum levels of homocysteine and indoxyl sulfate. Another small-scale study from Japan showed that synbiotics containing lactobacilli and can reduce serum level of p-Cresol in HD patients. High-serum p-cresyl sulfate and indoxyl sulfate levels were associated with renal progression. Serum concentrations of p-cresol are independently associated with overall mortality and cardiovascular disease in HD patients. The aim of the study is 1. to evaluate the difference of intestinal microflora between CKD patients and healthy controls; 2. to evaluate whether the investigators can reduce cardiovascular events in CKD patients, and peritonitis in peritoneal dialysis (PD) patients, retard the progression of stage 3 and 4 CKD patients, and decrease circulating inflammatory markers(CRP, IL-6,IL-18, TNF-α), indoxyl sulfate, p-cresol and homocysteine after probiotics treatment. Randomized double blinded placebo control studies are performed in CKD patients. After informed consent, intervention group receives probiotics containing 109 CFU B. bifidum, B.catenulatum, B. longum, and L.plantarm), while placebo group receives corn starch. In the first year the investigators examine the 60 PD patients, in the second year the investigators do the 60 HD patients,and in the third year the investigators do the 60 stage 3 and 4 CKD patients. Primary endpoint is cardiovascular event, gastrointestinal symptoms, peritonitis in PD patients, and progression of stage 3 and 4 CKD. Values are compared between the groups by unpaired t test. X2 testis used to compare proportions between the groups. Relative risk and the number needed to treat, both with 95% CI, are used to describe the treatment effect of probiotics. A p value less than 0·05 is regarded as statistically significant.

Interventions

DIETARY_SUPPLEMENTProbiotics

intervention group receives probiotics containing 10E9 CFU B. bifidum, B. catenulatum, B. longgim, and L. plantarm in 6 months observations

DIETARY_SUPPLEMENTCornstarch

placebo will be given in 6 months

Sponsors

China Medical University Hospital
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes

Inclusion criteria

1. receiving peritoneal dialysis for more than 3 months, at least 18 years of age, and GFR \< 15 ml/min. 2. receiving hemodialysis dialysis for more than 3 months, at least 18 years of age, and GFR \< 15 ml/min. 3. Stage 3 and 4 CKD patients

Exclusion criteria

* active infectious conditions within the last 30 days, * pregnancy for female, * autoimmune disease e.g. SLE., * cardiovascular events before.

Design outcomes

Primary

MeasureTime frame
the Occurrence of Cardiovascular Event and Peritonitis Events6 month follow-up

Secondary

MeasureTime frameDescription
Change of Gastrointestinal Symptoms at 6 Months6 months follow-upThe change in gastrointestinal symptom rating scale (min and maximum scores 0-45) after treatment. The total score is reported. The higher scale represents a worse outcome.

Countries

Taiwan

Participant flow

Participants by arm

ArmCount
Placebo
Cornstarch: placebo will be given in 6 months
24
Probiotics
Probiotics: intervention group receives probiotics containing 10E9 CFU B. bifidum, B. catenulatum, B. longgim, and L. plantarm in 6 months observations
23
Total47

Baseline characteristics

CharacteristicPlaceboProbioticsTotal
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
0 Participants0 Participants0 Participants
Age, Categorical
Between 18 and 65 years
24 Participants23 Participants47 Participants
IL-65.27 pg/ml
STANDARD_DEVIATION 12.78
6.55 pg/ml
STANDARD_DEVIATION 10.72
5.90 pg/ml
STANDARD_DEVIATION 11.71
Region of Enrollment
Taiwan
24 participants23 participants47 participants
Sex: Female, Male
Female
13 Participants12 Participants25 Participants
Sex: Female, Male
Male
11 Participants11 Participants22 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
0 / 230 / 24
serious
Total, serious adverse events
0 / 230 / 24

Outcome results

Primary

the Occurrence of Cardiovascular Event and Peritonitis Events

Time frame: 6 month follow-up

ArmMeasureGroupValue (NUMBER)
Placebothe Occurrence of Cardiovascular Event and Peritonitis EventsCardiovascular event0 participants
Placebothe Occurrence of Cardiovascular Event and Peritonitis EventsPeritonitis event0 participants
Probioticsthe Occurrence of Cardiovascular Event and Peritonitis EventsCardiovascular event0 participants
Probioticsthe Occurrence of Cardiovascular Event and Peritonitis EventsPeritonitis event0 participants
p-value: >0.05Chi-squared
Secondary

Change of Gastrointestinal Symptoms at 6 Months

The change in gastrointestinal symptom rating scale (min and maximum scores 0-45) after treatment. The total score is reported. The higher scale represents a worse outcome.

Time frame: 6 months follow-up

ArmMeasureValue (MEAN)Dispersion
PlaceboChange of Gastrointestinal Symptoms at 6 Months-2.82 units on a scaleStandard Deviation 5
ProbioticsChange of Gastrointestinal Symptoms at 6 Months-1.38 units on a scaleStandard Deviation 3.25
p-value: 0.744Wilcoxon (Mann-Whitney)
Post Hoc

Change of Serum Endotoxin Level at 6 Months

endotoxin is a marker of inflammation in chronic kidney disease patients

Time frame: 6 months follow-up

ArmMeasureValue (MEAN)Dispersion
PlaceboChange of Serum Endotoxin Level at 6 Months-1.31 EU/mlStandard Deviation 1.61
ProbioticsChange of Serum Endotoxin Level at 6 Months0.84 EU/mlStandard Deviation 2.27
p-value: 0.0042Wilcoxon (Mann-Whitney)
Post Hoc

Change of Serum IL-10 Level at 6 Months

IL-10 is an anti-inflammatory cytokine; The change of serum IL-10 level at 6 months was measured

Time frame: 6 months

ArmMeasureValue (MEAN)Dispersion
PlaceboChange of Serum IL-10 Level at 6 Months3.3 pg/mlStandard Deviation 6.37
ProbioticsChange of Serum IL-10 Level at 6 Months-2.09 pg/mlStandard Deviation 6.73
p-value: 0.0099Wilcoxon (Mann-Whitney)

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026