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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

U

University of Indonesia (UI)

Status

Unknown

Conditions

End Stage Renal Disease on Dialysis
Constipation

Treatments

Other: Placebo
Dietary Supplement: Synbiotics containing Lactobacillus acidophilus & Bifidobacterium longum 5x10^9 CFU and FOS 60 mg

Study type

Interventional

Funder types

Other

Identifiers

NCT04527640
20-07-0796

Details and patient eligibility

About

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.

Full 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.

Enrollment

60 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Supportive Care

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Triple Blind

60 participants in 2 patient groups, including a placebo group

Synbiotic Arm
Experimental group
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
Treatment:
Dietary Supplement: Synbiotics containing Lactobacillus acidophilus & Bifidobacterium longum 5x10^9 CFU and FOS 60 mg
Placebo Arm
Placebo Comparator group
Description:
Patients receiving placebo capsules containing saccharum lactis (2 capsules/day for 60 days)
Treatment:
Other: Placebo

Trial contacts and locations

0

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Central trial contact

Tities Indra, MD; Aida Lydia, MD, PhD

Data sourced from clinicaltrials.gov

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