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Impact of Propionic Acid on Regulatory T Cell Function in Children With CKD (Pro-Kids)

Primary Purpose

CKD (Chronic Kidney Disease) Stage 5D

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Sodium propionate
Placebo
Sponsored by
Charite University, Berlin, Germany
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for CKD (Chronic Kidney Disease) Stage 5D

Eligibility Criteria

12 Years - 20 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    PA Intervention

    Placebo Intervention

    Arm Description

    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.

    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.

    Outcomes

    Primary Outcome Measures

    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.

    Secondary Outcome Measures

    Propionic acid serum levels and targeted metabolomics
    Analysis of PA serum levels and other microbially-derived metabolites by GC-MS and LC-MS
    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).
    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.
    Single cell RNA sequencing of immune cells
    Analysis of the transcriptome of immune cells using cellular indexing of transcriptomes and epitopes (CITEseq)
    Intestinal barrier function
    Analysis of biomarkers for intestinal barrier function, such as sCD14, zonulin-1 and LPS
    Taxonomy of the fecal microbiome
    The taxonomy of the fecal microbiome will be anayzed using 16S RNA amplicon sequencing.

    Full Information

    First Posted
    April 25, 2023
    Last Updated
    August 29, 2023
    Sponsor
    Charite University, Berlin, Germany
    Collaborators
    University Hospital Heidelberg, University Hospital, Essen, University Hospital of Cologne, Universitätsklinikum Hamburg-Eppendorf
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05858437
    Brief Title
    Impact of Propionic Acid on Regulatory T Cell Function in Children With CKD
    Acronym
    Pro-Kids
    Official Title
    Impact of Propionic Acid on Regulatory T Cell Function in Children With Chronic Kidney Disease
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 1, 2023 (Anticipated)
    Primary Completion Date
    June 2024 (Anticipated)
    Study Completion Date
    September 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Charite University, Berlin, Germany
    Collaborators
    University Hospital Heidelberg, University Hospital, Essen, University Hospital of Cologne, Universitätsklinikum Hamburg-Eppendorf

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    CKD (Chronic Kidney Disease) Stage 5D

    7. Study Design

    Primary Purpose
    Basic Science
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Model Description
    randomized, double-blind, placebo-controlled
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    16 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    PA Intervention
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    Placebo Intervention
    Arm Type
    Placebo Comparator
    Arm Description
    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.
    Intervention Type
    Dietary Supplement
    Intervention Name(s)
    Sodium propionate
    Intervention Description
    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.
    Intervention Type
    Other
    Intervention Name(s)
    Placebo
    Intervention Description
    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 Outcome Measure Information:
    Title
    Change in count of regulatory T-cells from baseline to week 4
    Description
    Analysis of Treg counts in whole blood (absolute quantification) and peripheral blood mononuclear cells (PBMC; relative quantification) by flow cytometry.
    Time Frame
    Baseline visit (week 0) in comparison to week 4
    Secondary Outcome Measure Information:
    Title
    Propionic acid serum levels and targeted metabolomics
    Description
    Analysis of PA serum levels and other microbially-derived metabolites by GC-MS and LC-MS
    Time Frame
    Baseline visit (week 0); Week 2; Week 4; Week 12
    Title
    Immune cell phenotyping of peripheral blood mononuclear cells (PBMC)
    Description
    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).
    Time Frame
    Baseline visit (week 0); Week 2; Week 4; Week 12
    Title
    T regulatory cell (Treg) suppression assay
    Description
    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.
    Time Frame
    Baseline visit (week 0); Week 4
    Title
    Single cell RNA sequencing of immune cells
    Description
    Analysis of the transcriptome of immune cells using cellular indexing of transcriptomes and epitopes (CITEseq)
    Time Frame
    Baseline visit (week 0); Week 4
    Title
    Intestinal barrier function
    Description
    Analysis of biomarkers for intestinal barrier function, such as sCD14, zonulin-1 and LPS
    Time Frame
    Baseline visit (week 0); Week 2; Week 4; Week 12
    Title
    Taxonomy of the fecal microbiome
    Description
    The taxonomy of the fecal microbiome will be anayzed using 16S RNA amplicon sequencing.
    Time Frame
    Baseline visit (week 0); Week 4

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    12 Years
    Maximum Age & Unit of Time
    20 Years
    Accepts Healthy Volunteers
    No
    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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Johannes Holle, Dr. med.
    Phone
    004930450516012
    Email
    johannes-benjamin.holle@charite.de
    First Name & Middle Initial & Last Name or Official Title & Degree
    Nicola Wilck, Dr. med.
    Phone
    004930450516012
    Email
    nicola.wilck@charite.de

    12. IPD Sharing Statement

    Learn more about this trial

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

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