Impacto do ácido propiônico na função reguladora das células T em crianças com DRC (Pro-Kids)
Impacto do ácido propiônico na função reguladora das células T em crianças com doença renal crônica
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.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
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.
Tipo de estudo
Inscrição (Estimado)
Estágio
- Não aplicável
Contactos e Locais
Contato de estudo
- Nome: Johannes Holle, Dr. med.
- Número de telefone: 004930450516012
- E-mail: johannes-benjamin.holle@charite.de
Estude backup de contato
- Nome: Nicola Wilck, Dr. med.
- Número de telefone: 004930450516012
- E-mail: nicola.wilck@charite.de
Locais de estudo
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State of Berlin
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Berlin, State of Berlin, Alemanha, 13353
- Recrutamento
- Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charité-Universitätsmedizin Berlin
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Contato:
- Johannes Holle, MD
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Contato:
- Dominik Müller, MD
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
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
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Ciência básica
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Quadruplicar
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Experimental: 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. |
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Comparador de Placebo: 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. |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Change in count of regulatory T-cells from baseline to week 4
Prazo: 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 mononuclear cells (PBMC; relative quantification) by flow cytometry. |
Baseline visit (week 0) in comparison to week 4
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Propionic acid serum levels and targeted metabolomics
Prazo: Baseline visit (week 0); Week 2; Week 4; Week 12
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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; Week 12
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Immune cell phenotyping of peripheral blood mononuclear cells (PBMC)
Prazo: Baseline visit (week 0); Week 2; Week 4; Week 12
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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; Week 12
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T regulatory cell (Treg) suppression assay
Prazo: 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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Single cell RNA sequencing of immune cells
Prazo: 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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Intestinal barrier function
Prazo: Baseline visit (week 0); Week 2; Week 4; Week 12
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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; Week 12
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Taxonomy of the fecal microbiome
Prazo: 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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Cardiovascular Phenotyping
Prazo: Baseline visit (week 0); Week 2; Week 4; Week 12
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Analysis of heart rate over time. |
Baseline visit (week 0); Week 2; Week 4; Week 12
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Cardiovascular Phenotyping
Prazo: Baseline visit (week 0); Week 2; Week 4; Week 12
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Analysis of blood pressure over time. |
Baseline visit (week 0); Week 2; Week 4; Week 12
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Cholesterol levels
Prazo: Baseline visit (week 0); Week 2; Week 4; Week 12
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Cholesterol levels will be assessed using standard clinical lab values. |
Baseline visit (week 0); Week 2; Week 4; Week 12
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Colaboradores e Investigadores
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Real)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
- Doenças urogenitais
- Processos Patológicos
- Doenças Urogenitais Masculinas
- Doenças renais
- Doenças Urológicas
- Doenças Urogenitais Femininas
- Doenças urogenitais femininas e complicações na gravidez
- Doença crônica
- Atributos da doença
- Insuficiência renal
- Condições Patológicas, Sinais e Sintomas
- Insuficiência Renal Crônica
- Propionato de sódio
Outros números de identificação do estudo
- EA2/195/22
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