Clinical trial NCT05858437: Impact of Propionic Acid on Regulatory T Cell Function in Children With CKD
Official title: Impact of Propionic Acid on Regulatory T Cell Function in Children With Chronic Kidney Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: CKD (Chronic Kidney Disease) Stage 5D
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: University Hospital Heidelberg
name: University Hospital, Essen
name: University Hospital of Cologne
name: Universitätsklinikum Hamburg-Eppendorf
First posted: 2023-05-15
Enrollment: 16
Sex: ALL
Minimum age (years): 12
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized, double-blind, placebo-controlled
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in count of regulatory T-cells from baseline to week 4
timeFrame: Baseline visit (week 0) in comparison to week 4
Secondary outcomes:
measure: Propionic acid serum levels and targeted metabolomics
timeFrame: Baseline visit (week 0); Week 2; Week 4; Week 12
measure: Immune cell phenotyping of peripheral blood mononuclear cells (PBMC)
timeFrame: Baseline visit (week 0); Week 2; Week 4; Week 12
measure: T regulatory cell (Treg) suppression assay
timeFrame: Baseline visit (week 0); Week 4
measure: Single cell RNA sequencing of immune cells
timeFrame: Baseline visit (week 0); Week 4
measure: Intestinal barrier function
timeFrame: Baseline visit (week 0); Week 2; Week 4; Week 12
measure: Taxonomy of the fecal microbiome
timeFrame: Baseline visit (week 0); Week 4
measure: Cardiovascular Phenotyping
timeFrame: Baseline visit (week 0); Week 2; Week 4; Week 12
measure: Cardiovascular Phenotyping
timeFrame: Baseline visit (week 0); Week 2; Week 4; Week 12
measure: Cholesterol levels
timeFrame: Baseline visit (week 0); Week 2; Week 4; Week 12
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charité-Universitätsmedizin Berlin
Study officials:
References: