Impact of Propionic Acid on Regulatory T Cell Function in Children With CKD

CKD (Chronic Kidney Disease) Stage 5D Clinical Trial

— Pro-Kids  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05858437
• Other study ID #: EA2/195/22
• Status: Recruiting
• Phase: N/A
• Start date: January 15, 2024
• Est. completion date: September 2024

Study information

• Verified date: March 2024
• Source: Charite University, Berlin, Germany
• Contact: Johannes Holle, Dr. med.
• Phone: 004930450516012
• Email: johannes-benjamin.holle[@]charite.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 16
• Est. completion date: September 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 20 Years

Eligibility

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

Related Conditions & MeSH terms

• CKD (Chronic Kidney Disease) Stage 5D
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

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.

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.

Locations

Country	Name	City	State
Germany	Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charité-Universitätsmedizin Berlin	Berlin

Sponsors (5)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany	Universitätsklinikum Hamburg-Eppendorf, University Hospital Heidelberg, University Hospital of Cologne, University Hospital, Essen

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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