Clinical trial NCT04527640: 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
Overall status: UNKNOWN
Phase: NA
Conditions: Constipation
End Stage Renal Disease on Dialysis
Keywords: Synbiotics
Indoxyl Sulfate
Constipation
Quality of life
Dysbiosis
End-Stage Renal Disease
Hemodialysis
Lead sponsor: Indonesia University
Sponsor class: OTHER
First posted: 2020-08-26
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: SUPPORTIVE_CARE

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.

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

Primary outcomes:
measure: Indoxyl Sulfate concentration
timeFrame: Through study completion, an average of 60 days
Secondary outcomes:
measure: Symptoms of constipation
timeFrame: Through study completion, an average of 60 days
measure: Constipation-related quality of life
timeFrame: Through study completion, an average of 60 days
Other outcomes:
Locations:
Study officials:
affiliation: Indonesia University
name: Aida Lydia, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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