CKD (Chronic Kidney Disease) Stage 5D
Conditions
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.
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.
Interventions
DIETARY_SUPPLEMENTSodium 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.
OTHERPlacebo
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.
Sponsors
University Hospital Heidelberg
University Hospital, Essen
University Hospital of Cologne
Universitätsklinikum Hamburg-Eppendorf
Charite University, Berlin, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
randomized, double-blind, placebo-controlled
Eligibility
Sex/Gender
ALL
Age
12 Years to 20 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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 |
| 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. |
| Cardiovascular Phenotyping | Baseline visit (week 0); Week 2; Week 4; Week 12 | Analysis of heart rate over time. |
| Cholesterol levels | Baseline visit (week 0); Week 2; Week 4; Week 12 | Cholesterol levels will be assessed using standard clinical lab values. |
| 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 |
Countries
Germany
Contacts
Primary ContactJohannes Holle, Dr. med.
Backup ContactNicola Wilck, Dr. med.
Outcome results
None listed