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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Kidney Disease 5D
• Intervention / Treatment: Dietary supplement: Inulin; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Victoria McParland, PhD; Phone Number: +49 30 450 540 464; Email: victoria.mcparland@charite.de

Study Locations

• Germany
  • Berlin, Germany, 13125
    • Recruiting
    • Experimental and Clinical Research Center
    • Contact: Victoria McParland, PhD; Phone Number: +4930450540464; Email: victoria.mcparland@charite.de
    • Contact: Nicola Wilck, MD; Phone Number: +4930450540459; Email: nicola.wilck@charite.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Changes applied in January 2024 according to amendment no. 2:

• One inclusion criteria was changed to improve recruitment

  • BMI range was changed from 25 - 39,9 to 18,5 - 39,9 kg/m²
• Last visit was brought foward by 4 weeks.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Inulin; 15 grams inulin per day for 7 days, followed by 30 grams inulin per day for 28 days	Dietary supplement: Inulin; 1 sachet à 15 grams daily for 7 days, followed by 2 sachets à 15 grams daily for 28 days
Placebo Comparator: Placebo; 15 grams maltodextrin per day for 7 days, followed by 30 grams maltodextrin per day for 28 days	Dietary supplement: Placebo; 1 sachet à 15 grams daily for 7 days, followed by 2 sachets à 15 grams daily for 28 days

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Investigators: Principal Investigator: Anja Mähler, PhD, Charite University, Berlin, Germany; Principal Investigator: Nicola Wilck, MD, Charite University, Berlin, Germany; Principal Investigator: Victoria McParland, PhD, Charite University, Berlin, Germany; Principal Investigator: Johannes Holle, MD, Charite University, Berlin, Germany

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2022
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: September 16, 2021
• First Submitted That Met QC Criteria: September 27, 2021
• First Posted (Actual): October 8, 2021

Study Record Updates

• Last Update Posted (Actual): June 25, 2024
• Last Update Submitted That Met QC Criteria: June 24, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Fiber; Hemodialysis; Short chain fatty acids; Zonulin; Dietary analysis
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: RESTORE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results of reported articles (text, tables, figures, supplemental data) will be shared after deidentification.
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication.
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No