Impact of Propionic Acid on Regulatory T Cell Function in Children With CKD (Pro-Kids)

Impact of Propionic Acid on Regulatory T Cell Function in Children With Chronic Kidney Disease

Pro-Kids is a multi-center, double-blind, randomized and placebo-controlled intervention study in children with chronic kidney disease. The investigators address the effect of a dietary food supplementation of propionic acid on the immune system and the function of the intestinal barrier in CKD patients treated with hemodialysis.

Study Overview

• Status: Recruiting
• Conditions: CKD (Chronic Kidney Disease) Stage 5D
• Intervention / Treatment: Dietary supplement: Sodium propionate; Other: Placebo

Detailed Description

Chronic inflammation is a major risk factor of cardiovascular disease progression in CKD, irrespective of confounding comorbidities. Based on current knowledge, microbially-derived metabolites such as short chain fatty acids (SCFA) play an important role in the regulation of chronic inflammatory processes in CKD patients. Children with CKD are known to have reduced serum levels of the SCFA propionic acid (PA), as a consequence of both gut microbial dysbiosis and reduced fiber intake. In animal and human studies the impact of PA on function and abundance of regulatory T cells (Treg) has been demonstrated. Consequently, the investigators aim to normalize the PA serum levels by oral PA food supplementation in hemodialysis patients in order to mitigate chronic inflammation.

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Johannes Holle, Dr. med.; Phone Number: 004930450516012; Email: johannes-benjamin.holle@charite.de
• Study Contact Backup: Name: Nicola Wilck, Dr. med.; Phone Number: 004930450516012; Email: nicola.wilck@charite.de

Study Locations

• Germany
  • Berlin, Germany, 13353
    • Recruiting
    • Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charité-Universitätsmedizin Berlin
    • Contact: Johannes Holle, MD
    • Contact: Dominik Müller, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Body weight: > 30kg
• CKD G5 treated with hemodialysis
• Continuous hemodialysis treatment for > 3 months
• Clinical stable condition
• Manifestation of CKD within childhood (<18 years)

Exclusion Criteria:

• Disease or dysfunctions, which disqualifies the patient
• Incapacity of contract or any other circumstances, which prohibit the patient or his legal guardians from understanding setup, meaning and entity of the study
• Acute infections
• Immunosuppressive therapy within the last 12 weeks before the start of the study
• Pre-/pro- or postbiotic or antibiotic therapy within the last 4 weeks before the start of the study
• Planned or unplanned hospitalization within in last 4 weeks before the start of the study or during study
• Malignant diseases
• Pregnancy
• chronic gastrointestinal or hepatic diseases (for example chronic inflammatory bowel disease
• alcohol- or drug abuse
• parallel participation on other interventional trials

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
Experimental: PA Intervention; The group which receives the PA as a dietary food supplement. A single capsule contains 500mg of sodiumpropionate, which is taken twice daily for 28 days.	Dietary supplement: Sodium propionate; The patients will be randomized to PA or placebo intervention (2:1 randomization). After the intervention of 28 days, we conduct an open-label study phase, where all patients are offered a dietary supplement of PA for overall 12 weeks (8 additional weeks for the intervention group and 12 weeks for the placebo group). By doing so we are giving every patient the opportunity to take PA and benefit from the possible positive impact on immunsystem and intestinal barrier function.
Placebo Comparator: Placebo Intervention; The control-group receives a placebo instead of propionate. The placebo contains maltodextrin and the same amount of sodium chloride as compared to the PA intervention. The placebo is taken twice per day for 28 days.	Other: Placebo; The patients will be randomized to PA or placebo intervention (2:1 randomization). After the intervention of 28 days, we conduct an open-label study phase, where all patients are offered a dietary supplement of PA for overall 12 weeks (8 additional weeks for the intervention group and 12 weeks for the placebo group). By doing so we are giving every patient the opportunity to take PA and benefit from the possible positive impact on immunsystem and intestinal barrier function.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in count of regulatory T-cells from baseline to week 4	Analysis of Treg counts in whole blood (absolute quantification) and peripheral blood mononuclear cells (PBMC; relative quantification) by flow cytometry.	Baseline visit (week 0) in comparison to week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Propionic acid serum levels and targeted metabolomics	Analysis of PA serum levels and other microbially-derived metabolites by GC-MS and LC-MS	Baseline visit (week 0); Week 2; Week 4; Week 12
Immune cell phenotyping of peripheral blood mononuclear cells (PBMC)	Patients PBMC will be thawed and immune cells we be analyzed using multicolor flow cytometry and mass cytometry. By using a broad range of different antibodies combined in several panels the investigators will analyse distinct T cell subtypes including markers of activation, but also other immune cells (including B cells, dendritic cells, monocytes, natural killer cells). Data will reported in relation to parent populations (e.g. T heller cells in % of T cells).	Baseline visit (week 0); Week 2; Week 4; Week 12
T regulatory cell (Treg) suppression assay	The suppressive capacity of patients Treg will be analyzed by co-cultivation with conventional, stimulated T cells (Tconv) in different proportions (Treg:Tconv). The proliferation of Tconv will be reported.	Baseline visit (week 0); Week 4
Single cell RNA sequencing of immune cells	Analysis of the transcriptome of immune cells using cellular indexing of transcriptomes and epitopes (CITEseq)	Baseline visit (week 0); Week 4
Intestinal barrier function	Analysis of biomarkers for intestinal barrier function, such as sCD14, zonulin-1 and LPS	Baseline visit (week 0); Week 2; Week 4; Week 12
Taxonomy of the fecal microbiome	The taxonomy of the fecal microbiome will be anayzed using 16S RNA amplicon sequencing.	Baseline visit (week 0); Week 4
Cardiovascular Phenotyping	Analysis of heart rate over time.	Baseline visit (week 0); Week 2; Week 4; Week 12
Cardiovascular Phenotyping	Analysis of blood pressure over time.	Baseline visit (week 0); Week 2; Week 4; Week 12
Cholesterol levels	Cholesterol levels will be assessed using standard clinical lab values.	Baseline visit (week 0); Week 2; Week 4; Week 12

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Collaborators: University Hospital, Essen; University Hospital Heidelberg; Universitätsklinikum Hamburg-Eppendorf; University Hospital of Cologne

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2024
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: April 25, 2023
• First Submitted That Met QC Criteria: May 4, 2023
• First Posted (Actual): May 15, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 14, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: EA2/195/22

Drug and device information, study documents

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