Pro-Kids: Impact of Propionic Acid on Regulatory T Cell Function in Children With CKD
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
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 Design
Arms and Interventions
| 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.
|
Outcome Measures
Primary Outcome Measures
- Change in count of regulatory T-cells from baseline to week 4 [Baseline visit (week 0) in comparison to week 4]
Analysis of Treg counts in whole blood (absolute quantification) and peripheral blood mononuclear cells (PBMC; relative quantification) by flow cytometry.
Secondary Outcome Measures
- Propionic acid serum levels and targeted metabolomics [Baseline visit (week 0); Week 2; Week 4; Week 12]
Analysis of PA serum levels and other microbially-derived metabolites by GC-MS and LC-MS
- Immune cell phenotyping of peripheral blood mononuclear cells (PBMC) [Baseline visit (week 0); Week 2; Week 4; Week 12]
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).
- T regulatory cell (Treg) suppression assay [Baseline visit (week 0); Week 4]
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.
- Single cell RNA sequencing of immune cells [Baseline visit (week 0); Week 4]
Analysis of the transcriptome of immune cells using cellular indexing of transcriptomes and epitopes (CITEseq)
- Intestinal barrier function [Baseline visit (week 0); Week 2; Week 4; Week 12]
Analysis of biomarkers for intestinal barrier function, such as sCD14, zonulin-1 and LPS
- Taxonomy of the fecal microbiome [Baseline visit (week 0); Week 4]
The taxonomy of the fecal microbiome will be anayzed using 16S RNA amplicon sequencing.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Body weight: > 30kg
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CKD G5 treated with hemodialysis
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Continuous hemodialysis treatment for > 3 months
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Clinical stable condition
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Manifestation of CKD within childhood (<18 years)
Exclusion Criteria:
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Disease or dysfunctions, which disqualifies the patient
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Incapacity of contract or any other circumstances, which prohibit the patient or his legal guardians from understanding setup, meaning and entity of the study
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Acute infections
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Immunosuppressive therapy within the last 12 weeks before the start of the study
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Pre-/pro- or postbiotic or antibiotic therapy within the last 4 weeks before the start of the study
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Planned or unplanned hospitalization within in last 4 weeks before the start of the study or during study
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Malignant diseases
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Pregnancy
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chronic gastrointestinal or hepatic diseases (for example chronic inflammatory bowel disease
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alcohol- or drug abuse
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parallel participation on other interventional trials
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Charite University, Berlin, Germany
- University Hospital Heidelberg
- University Hospital, Essen
- University Hospital of Cologne
- Universitätsklinikum Hamburg-Eppendorf
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- EA2/195/22