Impacto del ácido propiónico en la función de las células T reguladoras en niños con ERC (Pro-Kids)
Impacto del ácido propiónico en la función reguladora de las células T en niños con enfermedad renal crónica
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.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
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 estudio
Inscripción (Estimado)
Fase
- No aplica
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Johannes Holle, Dr. med.
- Número de teléfono: 004930450516012
- Correo electrónico: johannes-benjamin.holle@charite.de
Copia de seguridad de contactos de estudio
- Nombre: Nicola Wilck, Dr. med.
- Número de teléfono: 004930450516012
- Correo electrónico: nicola.wilck@charite.de
Ubicaciones de estudio
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State of Berlin
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Berlin, State of Berlin, Alemania, 13353
- Reclutamiento
- Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charité-Universitätsmedizin Berlin
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Contacto:
- Johannes Holle, MD
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Contacto:
- Dominik Müller, MD
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
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
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Ciencia básica
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Cuadruplicar
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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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 placebos: 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. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Change in count of regulatory T-cells from baseline to week 4
Periodo de tiempo: 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 resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Propionic acid serum levels and targeted metabolomics
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Enfermedades urogenitales
- Procesos Patológicos
- Enfermedades urogenitales masculinas
- Enfermedades Renales
- Enfermedades urológicas
- Enfermedades urogenitales femeninas
- Enfermedades urogenitales femeninas y complicaciones del embarazo
- Enfermedad crónica
- Atributos de la enfermedad
- Insuficiencia renal
- Condiciones Patológicas, Signos y Síntomas
- Insuficiencia Renal Crónica
- propionato de sodio
Otros números de identificación del estudio
- EA2/195/22
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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