Effects of Synbiotics Supplementation on the Uremic Toxin Indoxyl Sulfate Level and Constipation in End-stage Renal Disease Patients Undergoing Hemodialysis
Primary Purpose
Constipation, End Stage Renal Disease on Dialysis
Status
Unknown status
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Synbiotics containing Lactobacillus acidophilus & Bifidobacterium longum 5x10^9 CFU and FOS 60 mg
Placebo
Sponsored by
About this trial
This is an interventional supportive care trial for Constipation focused on measuring Synbiotics, Indoxyl Sulfate, Constipation, Quality of life, Dysbiosis, End-Stage Renal Disease, Hemodialysis
Eligibility Criteria
Inclusion Criteria:
- Aged more than 18 years old
- Had undergone hemodialysis twice a week for a minimum of 3 months, with each visit lasting 5 hours
- Had only undergone hemodialysis therapy (not peritoneal dialysis/kidney transplantation)
- No history of malignancy or undergoing chemotherapy/radiation therapy
- No history of autoimmune disease or consuming immunosuppressants
- No history of bowel resection
- Had never been diagnosed with Crohn's disease or ulcerative colitis
Exclusion Criteria:
- Patients whose hemodialysis schedule was changed from twice a week to three times a week
- Patients consuming prebiotics/probiotics/synbiotics within the past 3 weeks
- Patients experiencing infection or is consuming antibiotics
- Patients who are not willing to participate
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Synbiotic Arm
Placebo Arm
Arm Description
Patients receiving synbiotics: Lactobacillus acidophilus & Bifidobacterium longum 5x10^9 Colony Forming Unit (CFU) and Fructooligosaccharides (FOS) 60 mg, 2 capsules/day for 60 days
Patients receiving placebo capsules containing saccharum lactis (2 capsules/day for 60 days)
Outcomes
Primary Outcome Measures
Indoxyl Sulfate concentration
Concentration of indoxyl sulfates in the subjects' blood samples
Secondary Outcome Measures
Symptoms of constipation
Constipation-related symptoms as assessed using Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire. Score will be assessed at the start and at the end of the study. Symptoms will be considered improved if there is a reduction of total score by 1 or more point(s).
Constipation-related quality of life
Constipation-related quality of life as assessed using Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaire. Score will be assessed at the start and at the end of the study. Quality of life will be considered improved if there is a reduction of total score by 1 or more point(s).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04527640
Brief Title
Effects of Synbiotics Supplementation on the Uremic Toxin Indoxyl Sulfate Level and Constipation in End-stage Renal Disease Patients Undergoing Hemodialysis
Official Title
Effects of Synbiotics Supplementation on the Concentration of the Uremic Toxin Indoxyl Sulfate, Symptoms of Constipation, and Constipation-related Quality of Life in End-stage Renal Disease Patients Undergoing Hemodialysis
Study Type
Interventional
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Unknown status
Study Start Date
September 15, 2020 (Anticipated)
Primary Completion Date
January 31, 2021 (Anticipated)
Study Completion Date
February 28, 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Indonesia University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a double-blind, placebo-controlled, randomized clinical trial conducted to evaluate the effects of synbiotics supplementation on the level of the uremic toxin indoxyl sulfate, symptoms of constipation, and constipation-related quality of life in end-stage renal disease patients undergoing hemodialysis.
Detailed Description
One of the most common gastrointestinal symptoms in end-stage renal disease patients undergoing hemodialysis is constipation, which is one of the risk factors of microbiota dysbiosis. One effect of dysbiosis is the increased level of a uremic toxin known as indoxyl sulfate. The accumulated concentration of indoxyl sulfate in end-stage renal disease patients undergoing hemodialysis is associated with inflammation and oxidative stress, which in turn increases the risk of cardiovascular event. Constipation and an increased risk of cardiovascular event is associated with low quality of life in chronic kidney disease patients undergoing hemodialysis.
Synbiotics administrations had become one of the many ways to improve gut dysbiosis as it is expected to lower the level of indoxyl sulfate and improve the symptoms of constipation and constipation-related quality of life. Although studies had investigated the role of probiotics/prebiotics/synbiotics, the role of synbiotics in lowering the concentration of the uremic toxin indoxyl sulfate remains inconclusive. Therefore, this study is conducted to demonstrate the benefits of synbiotics administration in lowering the concentration of indoxyl sulfate in end-stage renal disease patients undergoing hemodialysis, This is the first study in Indonesia investigating the effects of synbiotics supplementation in end-stage renal disease patients undergoing hemodialysis.
This study is a double-blind, placebo-controlled, randomized clinical trial conducted on end-stage renal disease patients undergoing hemodialysis. Patients will be divided into two arms: synbiotics and placebo. The study will take place in the hemodialysis unit of Dr. Cipto Mangunkusumo General Hospital in September 2020 to February 2021. A total of 60 participants will be recruited for the study (30 in each arm), who will be randomized into the synbiotic arm or the placebo arm. Both investigators and patients will be blinded to the treatment, and blinding will be conducted by the pharmacy unit of Dr. Cipto Mangunkusumo General Hospital.
Patients who had consented to participate will be assessed for medical history and physical examination. Food recall evaluation will also be performed by a nutritionist. Blood samples will be collected from the patient for laboratory examinations, including haemoglobin, white blood cells (WBC), platelet, urea, creatinine, albumin, and indoxyl sulfate. Patients will also be asked to complete two questionnaires: the Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire to assess the symptoms of constipation and the Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaire to assess constipation-related quality of life. After this, patients will be randomized into one of the two study arms. The data will serve as baseline data.
Patients will receive 2 capsules containing either synbiotics or placebo per day for the next 30 days. Afterwards, the patients will undergo examination to evaluate food recall and side effects. After evaluation, the patients will once again receive 2 capsules containing either synbiotics or placebo per day for the next 30 days, and after a total 2 months of interventions, will undergo examinations similar to that done in baseline examination.
The primary outcome of this study is the concentration of indoxyl sulfate in end-stage renal disease patients undergoing hemodialysis. Secondary outcomes include the symptoms of constipation and constipation-related quality of life in end-stage renal disease patients undergoing hemodialysis.
This study will be done according to the principles detailed in Helsinki declaration, Guideline for Good Clinical Practice from ICH Tripartite Guideline (ICH-GCP), and had been approved by the Ethical Committee of the Faculty of Medicine of Indonesia University.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Constipation, End Stage Renal Disease on Dialysis
Keywords
Synbiotics, Indoxyl Sulfate, Constipation, Quality of life, Dysbiosis, End-Stage Renal Disease, Hemodialysis
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
This study is a double-blind, placebo-controlled, randomized clinical trial conducted on end-stage renal disease patients undergoing hemodialysis. Patients will be randomized into two arms: symbiotic and placebo. The study will take place in the hemodialysis unit of Dr. Cipto Mangunkusumo General Hospital in September 2020 to February 2021. A total of 60 participants will be recruited for the study (30 in each arm). Both investigators and patients will be blinded to the treatment, and blinding will be conducted by the pharmacy unit of Dr. Cipto Mangunkusumo General Hospital.
Masking
ParticipantCare ProviderInvestigator
Masking Description
Masking is done for participants, care provider, and investigator. Masking is assigned by the pharmacy unit of Dr. Cipto Mangunkusumo Hospital.
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Synbiotic Arm
Arm Type
Experimental
Arm Description
Patients receiving synbiotics: Lactobacillus acidophilus & Bifidobacterium longum 5x10^9 Colony Forming Unit (CFU) and Fructooligosaccharides (FOS) 60 mg, 2 capsules/day for 60 days
Arm Title
Placebo Arm
Arm Type
Placebo Comparator
Arm Description
Patients receiving placebo capsules containing saccharum lactis (2 capsules/day for 60 days)
Intervention Type
Dietary Supplement
Intervention Name(s)
Synbiotics containing Lactobacillus acidophilus & Bifidobacterium longum 5x10^9 CFU and FOS 60 mg
Intervention Description
Patients will undergo baseline examination including medical history and physical examination, blood samples will be collected for hemoglobin, WBC, platelet, urea, creatinine, albumin and indoxyl sulfate level. Patients will be asked to complete 2 questionnaires the PAC-SYM and PAC-QOL questionnaires, and will undergo food recall evaluations by a nutritionist. They will then be given 2 capsules of synbiotics per day for 30 days. After 1 month of intervention, the patients will be evaluated for food recall and side effects. Afterwards, the patients will receive 2 capsules of the same synbiotics per day for the next 30 days. After 2 months of intervention, the patients' history will be taken, they will be asked to complete the PAC-SYM and PAC-QOL questionnaires, undergo food recall examination, and side effects evaluation. Blood samples will be taken for indoxyl sulfate examination.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Patients will undergo baseline examination including medical history and physical examination, blood samples will be collected for hemoglobin, WBC, platelet, urea, creatinine, albumin and indoxyl sulfate level. Patients will be asked to complete 2 questionnaires the PAC-SYM and PAC-QOL questionnaires, and will undergo food recall evaluations by a nutritionist. They will then be given 2 capsules of placebo per day for 30 days. After 1 month of intervention, the patients will be evaluated for food recall and side effects. Afterwards, the patients will receive 2 capsules of the same placebo per day for the next 30 days. After 2 months of intervention, the patients' history will be taken, they will be asked to complete the PAC-SYM and PAC-QOL questionnaires, undergo food recall examination, and side effects evaluation. Blood samples will be taken for indoxyl sulfate examination.
Primary Outcome Measure Information:
Title
Indoxyl Sulfate concentration
Description
Concentration of indoxyl sulfates in the subjects' blood samples
Time Frame
Through study completion, an average of 60 days
Secondary Outcome Measure Information:
Title
Symptoms of constipation
Description
Constipation-related symptoms as assessed using Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire. Score will be assessed at the start and at the end of the study. Symptoms will be considered improved if there is a reduction of total score by 1 or more point(s).
Time Frame
Through study completion, an average of 60 days
Title
Constipation-related quality of life
Description
Constipation-related quality of life as assessed using Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaire. Score will be assessed at the start and at the end of the study. Quality of life will be considered improved if there is a reduction of total score by 1 or more point(s).
Time Frame
Through study completion, an average of 60 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Aged more than 18 years old
Had undergone hemodialysis twice a week for a minimum of 3 months, with each visit lasting 5 hours
Had only undergone hemodialysis therapy (not peritoneal dialysis/kidney transplantation)
No history of malignancy or undergoing chemotherapy/radiation therapy
No history of autoimmune disease or consuming immunosuppressants
No history of bowel resection
Had never been diagnosed with Crohn's disease or ulcerative colitis
Exclusion Criteria:
Patients whose hemodialysis schedule was changed from twice a week to three times a week
Patients consuming prebiotics/probiotics/synbiotics within the past 3 weeks
Patients experiencing infection or is consuming antibiotics
Patients who are not willing to participate
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Aida Lydia, MD, PhD
Phone
+62 812-102-8939
Email
draidalydia@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Tities Indra, MD
Phone
+62 8111-288-300
Email
drtities@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Aida Lydia, MD, PhD
Organizational Affiliation
Indonesia University
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
No plan to share individual participant data
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Effects of Synbiotics Supplementation on the Uremic Toxin Indoxyl Sulfate Level and Constipation in End-stage Renal Disease Patients Undergoing Hemodialysis
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