Indvirkning af propionsyre på regulatorisk T-cellefunktion hos raske voksne (Pro-Health) (Pro-Health)
Indvirkning af propionsyre på regulatorisk T-cellefunktion hos raske voksne.
Pro-Health is a single-center, double-blind, randomized and placebo-controlled intervention study in healthy adults. 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 healhty adults.
Studieoversigt
Status
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
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. Patients 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 increase the PA serum levels by oral PA food supplementation in healthy adults in order to perspectively intervene with the same strategy in patients with CKD in the near future, with the target to increase abundance and function of antiinflammatory cells.
Undersøgelsestype
Tilmelding (Anslået)
Fase
- Ikke anvendelig
Kontakter og lokationer
Studiesteder
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State of Berlin
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Berlin, State of Berlin, Tyskland, 13353
- Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charité-Universitätsmedizin Berlin
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
- 18 - 40 years old
- Body weight: > 30kg
Exclusion Criteria:
- Disease or dysfunctions, which disqualifies the patient
- Incapacity of contract or any other circumstances, which prohibit the patient 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
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Grundvidenskab
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Firedobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Placebo komparator: Placebo Intervention
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. |
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. |
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Eksperimentel: PA Intervention.
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 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.
Andre navne:
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Change in count of regulatory T-cells from baseline to week 4
Tidsramme: Baseline visit (week 0) in comparison to week 4
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Analysis of Treg counts in whole blood (absolute quantification) and peripheral blood |
Baseline visit (week 0) in comparison to week 4
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Single cell RNA sequencing of immune cells
Tidsramme: Baseline visit (week 0); Week 4
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Analysis of the transcriptome of immune cells using cellular indexing of transcriptomes and epitopes (CITEseq) |
Baseline visit (week 0); Week 4
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Taxonomy of the fecal microbiome
Tidsramme: Baseline visit (week 0); Week 4
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The taxonomy of the fecal microbiome will be anayzed using 16S RNA amplicon sequencing. |
Baseline visit (week 0); Week 4
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Propionic acid serum levels and targeted metabolomics
Tidsramme: Baseline visit (week 0); Week 2; Week 4
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Analysis of PA serum levels and other microbially-derived metabolites by GC-MS and LC-MS |
Baseline visit (week 0); Week 2; Week 4
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Relative abundance of different immune cell subsets with Immune cell phenotyping of peripheral blood mononuclear cells (PBMC)
Tidsramme: Baseline visit (week 0); Week 2; Week 4
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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
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Measuring the suppressive function of regulatory T cells (Tregs) as percentage of proliferated conventional CD4-positive T cells with an in vitro T regulatory cell (Treg) suppression assay
Tidsramme: Baseline visit (week 0); Week 4
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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
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Measuring the intestinal barrier function by measuring the concentration of different leaky gut markers
Tidsramme: Baseline visit (week 0); Week 2; Week 4
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Analysis of biomarkers for intestinal barrier function, such as sCD14, zonulin-1 and LPS |
Baseline visit (week 0); Week 2; Week 4
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Cardiovascular Phenothyping
Tidsramme: Baseline visit (week 0); Week 2; Week 4
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Analysis of heart rate over time. |
Baseline visit (week 0); Week 2; Week 4
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Cardiovascular Phenotyping
Tidsramme: Baseline visit (week 0); Week 2; Week 4
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Analysis of blood pressure over time. |
Baseline visit (week 0); Week 2; Week 4
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Cholesterol levels
Tidsramme: Baseline visit (week 0); Week 2; Week 4
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Cholestrol levels will be assessed using standard clinical lab values |
Baseline visit (week 0); Week 2; Week 4
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Samarbejdspartnere og efterforskere
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Faktiske)
Studieafslutning (Anslået)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- EA2/195/22 (2)
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
Studerer et amerikansk FDA-reguleret enhedsprodukt
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