Beneficial Effect of Probiotics on Chronic Kidney Disease

• Sponsor: China Medical University Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01391468
• Collaborator: (none)
• Enrollment: 47
• Location: 1
• Arms: 2
• Duration (Months): 28
• Patients Per Site Per Month: 1.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Disease	Dietary Supplement: Probiotics; Dietary Supplement: Cornstarch	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 47 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Beneficial Effect of Probiotics on Chronic Kidney Disease
• Study Start Date: Aug 1, 2011
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo cornstarch	Dietary Supplement: Cornstarch; placebo will be given in 6 months
Experimental: Probiotics probiotics	Dietary Supplement: Probiotics; intervention group receives probiotics containing 10E9 CFU B. bifidum, B. catenulatum, B. longgim, and L. plantarm in 6 months observations

Outcome Measures

Primary Outcome Measures

1. the Occurrence of Cardiovascular Event and Peritonitis Events [6 month follow-up]

Secondary Outcome Measures

1. Change of Gastrointestinal Symptoms at 6 Months [6 months follow-up]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	China Medical University Hospital	Taichung		Taiwan	413

Sponsors and Collaborators

• China Medical University Hospital

Investigators

• Principal Investigator: I-Kuan Wang, M.D., China Medical University Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: I-Kuan Wang, China Medical University Hospital, China Medical University Hospital
• ClinicalTrials.gov Identifier: NCT01391468
• Other Study ID Numbers: DMR-99-IRB-308
• First Posted: Jul 12, 2011
• Last Update Posted: Nov 3, 2015
• Last Verified: Oct 1, 2015

• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic

Study Results

Participant Flow

Arm/Group Title	Placebo	Probiotics
Arm/Group Description	Cornstarch: placebo will be given in 6 months	Probiotics: intervention group receives probiotics containing 10E9 CFU B. bifidum, B. catenulatum, B. longgim, and L. plantarm in 6 months observations
Period Title: Overall Study
STARTED	24	23
COMPLETED	18	21
NOT COMPLETED	6	2

Baseline Characteristics

Arm/Group Title	Placebo	Probiotics	Total
Arm/Group Description	Cornstarch: placebo will be given in 6 months	Probiotics: intervention group receives probiotics containing 10E9 CFU B. bifidum, B. catenulatum, B. longgim, and L. plantarm in 6 months observations	Total of all reporting groups
Overall Participants	24	23	47
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	24 100%	23 100%	47 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	13 54.2%	12 52.2%	25 53.2%
Male	11 45.8%	11 47.8%	22 46.8%
Region of Enrollment (participants) [Number]
Taiwan	24 100%	23 100%	47 100%
IL-6 (pg/ml) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [pg/ml]	5.27 (12.78)	6.55 (10.72)	5.90 (11.71)

Outcome Measures

1. Primary Outcome

Title	the Occurrence of Cardiovascular Event and Peritonitis Events
Time Frame	6 month follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Probiotics
Arm/Group Description	Cornstarch: placebo will be given in 6 months	Probiotics: intervention group receives probiotics containing 10E9 CFU B. bifidum, B. catenulatum, B. longgim, and L. plantarm in 6 months observations
Measure Participants	18	21
Cardiovascular event	0 0%	0 0%
Peritonitis event	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Probiotics
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	Chi-squared
	Comments

2. Secondary Outcome

Title	Change of Gastrointestinal Symptoms at 6 Months
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Probiotics
Arm/Group Description	cornstarch Cornstarch: placebo will be given in 6 months	probiotics Probiotics: intervention group receives probiotics containing 10E9 CFU B. bifidum, B. catenulatum, B. longgim, and L. plantarm in 6 months observations
Measure Participants	18	21
Mean (Standard Deviation) [units on a scale]	-2.82 (5)	-1.38 (3.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Probiotics
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.744
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Post-Hoc Outcome

Title	Change of Serum Endotoxin Level at 6 Months
Description	endotoxin is a marker of inflammation in chronic kidney disease patients
Time Frame	6 months follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Probiotics	Placebo
Arm/Group Description	probiotics Probiotics: intervention group receives probiotics containing 10E9 CFU B. bifidum, B. catenulatum, B. longgim, and L. plantarm in 6 months observations	Placeo group received maltodextrin for 6 months
Measure Participants	21	18
Mean (Standard Deviation) [EU/ml]	-1.31 (1.61)	0.84 (2.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0042
	Comments	Only the probiotics group arrived at the reported p-value after 6 months
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Post-Hoc Outcome

Title	Change of Serum IL-10 Level at 6 Months
Description	IL-10 is an anti-inflammatory cytokine; The change of serum IL-10 level at 6 months was measured
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Probiotics	Placebo
Arm/Group Description	probiotics Probiotics: intervention group receives probiotics containing 10E9 CFU B. bifidum, B. catenulatum, B. longgim, and L. plantarm in 6 months observations	Plabeco group received maltodextrin for 6 months
Measure Participants	21	18
Mean (Standard Deviation) [pg/ml]	3.3 (6.37)	-2.09 (6.73)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0099
	Comments	Only the probiotics group arrived at the reported p-value after 6 months
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Time Frame	1 month
Arm/Group Title	Probiotics		Placebo
Arm/Group Description	Probiotics: intervention group receives probiotics containing 10E9 CFU B. bifidum, B. catenulatum, B. longgim, and L. plantarm in 6 months observations		Cornstarch: placebo will be given in 6 months
All Cause Mortality
	Probiotics		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Probiotics		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	Probiotics		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/24 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.