Effect of Inulin on Gut Microbiota and Gut Barrier in Chronic Kidney Disease

Study Overview
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Brief Summary
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An adequate fiber intake is crucial for a well-balanced diet and reduces the risk of chronic diseases. However, nutritional recommendations for chronic kidney disease patients lead to an insufficient fiber intake with possible maladaptive effects on the gut microbiome. Therefore, we want to study the effects of a 35-day inulin supplementation on the gut microbiome, gut barrier function, bacterial metabolites and immune cell states in chronic kidney disease patients.

Official Title
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Investigating the Effect of Inulin on Gut Microbiota and Gut Barrier in Advanced Chronic Kidney Disease - a Randomised, Placebo-controlled Trial

Conditions
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Chronic Kidney Disease 5D

Intervention / Treatment
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* Dietary Supplement: Inulin
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women in a ratio of 1:1 Age 18-75 years Body mass index 25.0 - 39.9 kg/m^2 End-stage kidney disease, which has been treated regularly with hemodialysis for at least 3 months Exclusion Criteria: Malignant diseases Recent or current hospitalization Postoperative phase Acute infections Malnutrition Antibiotic treatment within the last 4 weeks Regular intake of probiotics and/or prebiotics Change of body weight of more than 2 kg in the month prior to study entry Known drug or alcohol abuse Changes applied in July 2022 according to amendment no. 1: Two inclusion criteria were changed to improve recruitment Age range was changed from 18-70 to 18-75 years BMI range was changed from 18.5 - 34.9 to 25.0 - 39.9 kg/m^2 The intervention scheme was adapted to increase patient adherence A 7-day adaption phase with half of the dose (15 grams per day) at the start of the intervention was introduced, changing treatment duration from 28 to 35 days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Inulin<br>15 grams inulin per day for 7 days, followed by 30 grams inulin per day for 28 days | Dietary Supplement: Inulin<br>* 1 sachet à 15 grams daily for 7 days, followed by 2 sachets à 15 grams daily for 28 days<br>|
| Placebo Comparator: Placebo<br>15 grams maltodextrin per day for 7 days, followed by 30 grams maltodextrin per day for 28 days | Dietary Supplement: Placebo<br>* 1 sachet à 15 grams daily for 7 days, followed by 2 sachets à 15 grams daily for 28 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration of Zonulin-1 | Measured by ELISA [ng/ml] | After 35 days compared to placebo | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration of soluble CD14 | Measured by ELISA [ng/ml] | After 35 days compared to placebo | 
| Short-chain fatty acid-associated bacterial gene expression | Measured by quantitative PCR | After 35 days compared to placebo and adjusted for baseline | 
| Short-chain fatty acid-associated gene expression in immune cells | Measured by quantitative PCR | After 35 days compared to placebo | 
| Indole-associated bacterial gene expression | Measured by quantitative PCR | After 35 days compared to placebo | 
| Indole-associated gene expression in immune cells | Measured by quantitative PCR | After 35 days compared to placebo | 
| Fecal metabolome | Measured by mass spectrometry | After 35 days compared to placebo and adjusted for baseline | 
| Serum metabolome | Measured by mass spectrometry | After 35 days compared to placebo | 
| Serum concentration of Trimethylamine-N-Oxide (TMAO) | Measured by LC-MS [µM] | After 35 days compared to placebo | 
| Fecal microbiome taxonomy | Measured by 16S amplicon sequencing | After 35 days compared to placebo | 
| Activation potential of aryl hydrocarbon receptor (AhR) in serum | Measured by cell-based luciferase reporter assay (delta luminescence) | After 35 days compared to placebo and adjusted for baseline | 
| Frequency of circulating T-cell subtypes | Measured by flow cytometry (%) | After 35 days compared to placebo | 
| Office systolic blood pressure | Mean of five consecutive blood pressure measurements (mmHg) | After 35 days compared to placebo | 
| Office diastolic blood pressure | Mean of five consecutive blood pressure measurements (mmHg) | After 35 days compared to placebo | 
| Plasma concentration of IL-1 | Measured by ELISA [pg/ml] | After 35 days compared to placebo | 
| Plasma concentration of IL-6 | Measured by ELISA [pg/ml] | After 35 days compared to placebo | 
| Plasma concentration of TNF-alpha | Measured by ELISA [pg/ml] | After 35 days compared to placebo | 
| Creatinine | Creatine serum concentration | After 35 days compared to placebo | 
| Cystatin c | Cystatin c serum concentration | After 35 days compared to placebo | 
| Creatinine / cystatin c ratio | Measured in serum | After 35 days compared to placebo | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemodialysis, Fiber, Zonulin, Short chain fatty acids, Dietary analysis