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NCT Number: NCT05858437

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

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.

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Key information

Conditions

CKD (Chronic Kidney Disease) Stage 5D Chronic Disease Disease Attributes Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Kidney Diseases Male Urogenital Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Renal Insufficiency Renal Insufficiency, Chronic Urogenital Diseases Urologic Diseases

Age range

12 year–20 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charité-Universitätsmedizin Berlin

Berlin, 13353, Germany

Location status: Recruiting

Location contact

Dominik Müller, MD

CONTACT

Johannes Holle, MD

CONTACT

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

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.

Primary outcomes

  1. Change in count of regulatory T-cells from baseline to week 4

    Time frame: 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 outcomes

  1. Propionic acid serum levels and targeted metabolomics

    Time frame: 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

  2. Immune cell phenotyping of peripheral blood mononuclear cells (PBMC)

    Time frame: 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).

  3. T regulatory cell (Treg) suppression assay

    Time frame: 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.

  4. Single cell RNA sequencing of immune cells

    Time frame: Baseline visit (week 0); Week 4

    Analysis of the transcriptome of immune cells using cellular indexing of transcriptomes and epitopes (CITEseq)

  5. Intestinal barrier function

    Time frame: Baseline visit (week 0); Week 2; Week 4; Week 12

    Analysis of biomarkers for intestinal barrier function, such as sCD14, zonulin-1 and LPS

  6. Taxonomy of the fecal microbiome

    Time frame: Baseline visit (week 0); Week 4

    The taxonomy of the fecal microbiome will be anayzed using 16S RNA amplicon sequencing.

  7. Cardiovascular Phenotyping

    Time frame: Baseline visit (week 0); Week 2; Week 4; Week 12

    Analysis of heart rate over time.

  8. Cardiovascular Phenotyping

    Time frame: Baseline visit (week 0); Week 2; Week 4; Week 12

    Analysis of blood pressure over time.

  9. Cholesterol levels

    Time frame: Baseline visit (week 0); Week 2; Week 4; Week 12

    Cholesterol levels will be assessed using standard clinical lab values.

Study contacts

Contact information is provided by the study sponsor or research team.

Johannes Holle, Dr. med.

CONTACT

[email protected]

004930450516012

Nicola Wilck, Dr. med.

CONTACT

[email protected]

004930450516012

Sponsors and collaborators

Lead sponsor

Charite University, Berlin, Germany

Other

Collaborators

  • University Hospital Heidelberg
  • University Hospital of Cologne
  • University Hospital, Essen
  • Universitätsklinikum Hamburg-Eppendorf

Registry information

Official study title

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

Acronym: Pro-Kids

Important dates

Study start
2024
Primary completion
2025
Study completion
2026
First posted
May 15, 2023
Registry last updated
Feb 18, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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