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| Name | Class |
|---|---|
| University Hospital Heidelberg | OTHER |
| University Hospital, Essen | OTHER |
| University Hospital of Cologne | OTHER |
| Universitätsklinikum Hamburg-Eppendorf |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PA Intervention | Experimental | 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. |
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| Placebo Intervention | Placebo Comparator | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sodium propionate | Dietary Supplement | 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. |
| 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 |
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Johannes Holle, Dr. med. | Contact | 004930450516012 | johannes-benjamin.holle@charite.de | |
| Nicola Wilck, Dr. med. | Contact | 004930450516012 | nicola.wilck@charite.de |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charité-Universitätsmedizin Berlin | Recruiting | Berlin | 13353 | Germany |
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| ID | Term |
|---|---|
| D051436 | Renal Insufficiency, Chronic |
| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
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| ID | Term |
|---|---|
| C514135 | sodium propionate |
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| OTHER |
randomized, double-blind, placebo-controlled
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| Placebo | Other | 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. |
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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 |
| D005261 |
| Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |