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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Пищевая добавка Sodium propionate
  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.
• Другое Placebo
  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.

Первичные конечные точки

• Change in count of regulatory T-cells from baseline to week 4 [Срок оценки: Baseline visit (week 0) in comparison to week 4]

Вторичные конечные точки (9)

• Propionic acid serum levels and targeted metabolomics [Срок оценки: Baseline visit (week 0); Week 2; Week 4; Week 12]
• Immune cell phenotyping of peripheral blood mononuclear cells (PBMC) [Срок оценки: Baseline visit (week 0); Week 2; Week 4; Week 12]
• T regulatory cell (Treg) suppression assay [Срок оценки: Baseline visit (week 0); Week 4]
• Single cell RNA sequencing of immune cells [Срок оценки: Baseline visit (week 0); Week 4]
• Intestinal barrier function [Срок оценки: Baseline visit (week 0); Week 2; Week 4; Week 12]
• Taxonomy of the fecal microbiome [Срок оценки: Baseline visit (week 0); Week 4]
• Cardiovascular Phenotyping [Срок оценки: Baseline visit (week 0); Week 2; Week 4; Week 12]
• Cardiovascular Phenotyping [Срок оценки: Baseline visit (week 0); Week 2; Week 4; Week 12]
• Cholesterol levels [Срок оценки: Baseline visit (week 0); Week 2; Week 4; Week 12]

Критерии участия

Критерии включения

• Body weight: > 30kg
• CKD G5 treated with hemodialysis
• Continuous hemodialysis treatment for > 3 months
• Clinical stable condition
• Manifestation of CKD within childhood (<18 years)

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Фундаментальное исследование

Центры проведения

Германия · 1 центр

• Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charité-Unive — Berlin

Идентификаторы

NCT: NCT05858437 · EA2/195/22

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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