Gut Microbiome and p-Inulin in CKD - TarGut CKD Study

Study Overview
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Brief Summary
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The purpose of this Phase 1, 3-period crossover with repeated measures feasibility study is to characterize the gut microbiome of individuals with chronic kidney disease, and to explore effects of p-inulin on the gut microbiome. The nature of the study will provide information about the feasibility of stool sample collection for future multicenter studies of the gut microbiome.

Detailed Description
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The overarching hypothesis motivating this exploratory study of variability is that treatment with oligofructose-enriched inulin (p-inulin) will alter the composition and/or function of the gut microbiome, and thereby reduce the generation of gut-derived uremic toxins, improve gut barrier function and attenuate systemic inflammation in CKD patients. In order to design a future clinical trial the following parameters from CKD subjects are needed: Intra-patient variability in the composition and function of the gut microbiome Inter-patient variability in the composition and function of the gut microbiome Impact of p-inulin on the composition and function of the gut microbiome Tolerability of p-inulin administration Feasibility of collecting stool samples in this patient population

Official Title
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Gut Microbiome and p-Inulin in CKD TarGut CKD Study

Conditions
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Chronic Kidney Diseases

Intervention / Treatment
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* Dietary Supplement: Oligofructose-enriched inulin (p-inulin)
* Other: No treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with eGFR 15.0 to 50.0 ml/min/1.73 m2 as estimated by the CKD-EPI equation Albuminuria greater than 300 mg/g creatinine (by spot urine test) if eGFR is ≥45 ml/min/1.73 m2 Age ≥ 18 years For women of childbearing potential, willingness to use a highly effective method of birth control for up to 4 weeks after the last dose to study drug. See Section 4.2.1 for definition of childbearing potential and acceptable methods of birth control Ability to provide informed consent Exclusion Criteria: Use of pre- or pro-biotics during the past 2 months Consumption of probiotic yogurt during the past 2 weeks Use of antibiotics within the past 3 months if the patient received a single course of antibiotic. If the patient received more than one course of antibiotic treatment, we will wait for 6 months prior to inclusion. Presence of HIV infection, chronic wound infection and osteomyelitis Presence of or treatment for periodontal infection Inflammatory bowel disease, chronic diarrhea, current C. difficile infection Cirrhosis or chronic active hepatitis Treatment with immunosuppressive medications in the past 6 months or more than a week of treatment with prednisone >10 mg in the last 3 months Treatment with proton pump inhibitors within the last one month Anticipated initiation of dialysis or kidney transplant within 9 months Acute on chronic kidney disease Expected survival < 9 months Do not disclose or use except as authorized by the Pilot Clinical Trials in CKD Consortium. Pregnancy, anticipated pregnancy, or breastfeeding Incarceration Participation in another intervention study Severe anemia defined as hemoglobin <9.0 g/dl any time during the last 3 months Patients in whom frequent blood sampling may be difficult

Ages Eligible for Study
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Minimum Age: 18 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: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: This is a 28 week study. Participants take no treatment for 8 weeks, followed by 12 weeks on the pre-biotic p-inulin, followed by no treatment for 8 weeks. The treatment arms are no treatment and the pre-biotic p-inulin. Inulin is derived from chicory root fiber.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oligofructose-enriched inulin (p-inulin)<br>Participants are on no treatment for 8 weeks, then the pre-biotic p-inulin for 12 weeks, then no treatment for 8 weeks. Inulin is derived from chicory root fiber. The dose is 16 grams of p-inulin powder per day. | Dietary Supplement: Oligofructose-enriched inulin (p-inulin)<br> <br> Other: No treatment<br>* Patients do not take a supplement during the first 8 weeks or the last 8 weeks of the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbial composition of stool | Microbial taxonomy will be assigned using Ribosomal Database Project (RDP) for 16S, augmented by analysis of specific sequences using BLAST. The 16S tag sequences will be collected into operational taxonomic units (OTUs) with 97% sequence identity. | Stool is collected weekly for 28 weeks | 
| Adherence to p inulin prescription | Proportion of packets taken vs packets prescribed by packet count | Packets are counted every four weeks during the 12 weeks when the patient is taking p inulin | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| butyrate | captured by untargeted metabolomics, short chain fatty acid in stool blood and urine | Collected weekly for 28 weeks | 
| propionate | captured by untargeted metabolomics, short chain fatty acid in stool blood and urine | Collected weekly for 28 weeks | 
| acetate | captured by untargeted metabolomics, short chain fatty acid measured in stool blood and urine | Collected weekly for 28 weeks | 
| Trimethylamine N oxide | captured by untargeted metabolomics in stool blood and urine | Collected weekly for 28 weeks | 
| Choline | captured by untargeted metabolomics in stool blood and urine | Collected weekly for 28 weeks | 
| Betaine | captured by untargeted metabolomics in stool blood and urine | Collected weekly for 28 weeks | 
| Indoles | Indoxyl sulfate Indoxyl glucuronide 5-hydroxyindole Indole-3-prioonic acid Indole-3-acetic acid captured by untargeted metabolomics in stool blood and urine | collected weekly for 28 weeks | 
| Phenols | p-cresol sulfate p-Cresol glucuronide Phenyl sulfate Phenyl glucuronide α-N-phenylacetyl-L-glutamine Phenylpropionylglycine Hippuric acid 4-hydroxybenzoate Phenylacetylglycine * captured by untargeted metabolomics and quantitated by targeted metabolomics in stool blood urine | collected weekly for 28 weeks | 
| polyamines | captured by untargeted metabolomics in stool blood and urine | collected weekly for 28 weeks | 
| metabolites of urea and creatinine metabolism | captured by untargeted metabolomics in stool blood and urine | collected weekly for 28 weeks | 
| Allantoin | captured by untargeted metabolomics in stool blood and urine | collected weekly for 28 weeks | 
| Fructose | captured by untargeted metabolomics in stool blood and urine | collected weekly for 28 weeks | 
| Cytokines | IL-1β IL-2 IL-4 IL-6 IL-10 IL-17 IL-22 TNFα measured by standard ELISA in stool | collected weekly for 28 weeks | 
| endotoxin | measured by standard ELISA in stool | collected weekly for 28 weeks | 
| Myeloperoxdase (MPO) | measured by standard ELISA in stool | collected weekly for 28 weeks | 
| hsCRP | measured by standard ELISA in stool | collected weekly for 28 weeks | 
| HMGB1 | measured by standard ELISA in stool | collected weekly for 28 weeks | 
| TNF-R1 | measured by standard ELISA in stool | collected weekly for 28 weeks | 
| TNF-R2 | measured by standard ELISA in stool | collected weekly for 28 weeks | 
| Lipopolysaccharide binding protein (LBP) | measured by standard ELISA in stool | collected weekly for 28 weeks | 
| sCD14 | measured by standard ELISA in stool | collected weekly for 28 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Microbiome, p-inulin