Effect of Probiotics on Immunosuppressive-drug-associated Diarrhea Among Renal Transplant Recipients

Study Overview
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Brief Summary
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The goal of this pilot project is to 1) examine whether oral administration of probiotics are helpful in reducing immunosuppressive drugs-associated diarrhea and adhering to the required dose of immunosuppressive drugs and 2) determine how this treatment works by examining fecal microbiome and immunological markers among living and deceased donor renal transplant recipients. The main questions it aims to answer are: Does low dose probiotics effective in reducing immunosuppressive drugs-associated diarrhea? Does probiotics effective in reducing inflammation? Is there any connection between fecal microbiome and immunological markers? Participants will receive one probiotics capsule or placebo capsule daily for 6 months from the onset of diarrhea post-surgically. Researchers will compare the data obtained through probiotics group and placebo group to answer the above mentioned research questions.

Official Title
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Effect of Probiotics on Immunosuppressive-drug-associated Diarrhea Among Renal Transplant Recipients

Conditions
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Renal Transplantation

Intervention / Treatment
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* Other: Florajen Digestion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Received living or deceased donor kidney, subjects will be monitored peri-operatively Presence of mild to severe diarrhea (> 3 times loose stools/day); include type 6 and 7 in the Bristol Stool Chart. Has been on adjusted and/or maintenance dose of calcineurin inhibitors, antimetabolites and steroid regimen. Treatment of rejection including administration of steroids, intravenous immunoglobulin/plasmapheresis, rituximab and anti- thymocytes are also acceptable in this research. Exclusion Criteria: Pregnant and lactating women Has been receiving probiotics treatment Recurrence of gastrointestinal diseases including inflammatory bowel diseases, diverticulosis, irritable bowel syndrome. Had past surgical history of gastric bypass. Diagnosed with cancer Presence of infectious diarrhea, fever and high white blood cells (WBC) count. Infectious diarrhea is defined by polymerase chain reaction (PCR) negative for community acquired diarrhea panel [positive for Sapo virus, Noro virus, Clostridium difficile (positive for toxin A and B), Yersinia enterocolitica [(positive for toxin A and B) and enteropathogenic E. coli (positive Shiga toxins)].

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomized, double-blinded, placebo-controlled, single-center pilot/exploratory trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Probiotics Group<br>Participants will receive one probiotics capsule daily for six months immediately after the onset of post-surgical non-infectious diarrhea. | Other: Florajen Digestion<br>* Florajen Digestion is a probiotics. One probiotics capsule contains 15 billion Colony Forming Unit (CFU) of live microorganisms. No live microorganisms are present in the placebo capsules.<br>* Other names: Placebo;|
| Placebo Comparator: Placebo Group<br>Participants will receive one placebo capsule daily for six months immediately after the onset of post-surgical non-infectious diarrhea. | Other: Florajen Digestion<br>* Florajen Digestion is a probiotics. One probiotics capsule contains 15 billion Colony Forming Unit (CFU) of live microorganisms. No live microorganisms are present in the placebo capsules.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in immunosuppressive drugs-associated diarrhea | Gastrointestinal (GI) questionnaire and Bristol Stool Chart will be used to measure this outcome through Chi-Square test. | GI questionnaire and Bristol Stool Chart will be collected daily for six months from the onset of post-surgical, non-infectious diarrhea. | 
| Analysis of inflammatory biomarkers | Inflammatory biomarkers including TNF (tumor necrosis factor) superfamily proteins, IFN (interferon) family proteins, Treg cytokines and matrix metalloproteinases (MMP) [processed through Bio-Rad's Multiplex System) will be analyzed through general linear model analysis of variance (GLM ANOVA). | Whole blood will be collected three times for six months: baseline (on the day of transplant), 3 month and six month from the onset of post-surgical, non-infectious diarrhea. three and six months | 
| Association between inflammatory markers and fecal microbiome | Fecal microbial DNA will be analyzed through 16S PCR followed by Next-Gen sequencing. Pearson correlation analysis will be performed. | Stool samples will be collected seven times for six months: baseline (on the day of transplant), then monthly once from the onset of post-surgical, non-infectious diarrhea. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Probiotics, Immunosuppressive Drugs, Renal Transplantation, Diarrhea, Living Donor, Deceased Donor