CKDの小児における制御性T細胞機能に対するプロピオン酸の影響 (Pro-Kids)
慢性腎臓病の小児における制御性T細胞機能に対するプロピオン酸の影響
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.
調査の概要
詳細な説明
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.
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：Johannes Holle, Dr. med.
- 電話番号：004930450516012
- メール：johannes-benjamin.holle@charite.de
研究連絡先のバックアップ
- 名前：Nicola Wilck, Dr. med.
- 電話番号：004930450516012
- メール：nicola.wilck@charite.de
研究場所
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State of Berlin
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Berlin、State of Berlin、ドイツ、13353
- 募集
- Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charité-Universitätsmedizin Berlin
-
コンタクト：
- Johannes Holle, MD
-
コンタクト：
- Dominik Müller, MD
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-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：基礎科学
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：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. |
|
プラセボコンパレーター：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. |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Change in count of regulatory T-cells from baseline to week 4
時間枠：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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Propionic acid serum levels and targeted metabolomics
時間枠：Baseline visit (week 0); Week 2; Week 4; Week 12
|
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
|
|
Immune cell phenotyping of peripheral blood mononuclear cells (PBMC)
時間枠：Baseline visit (week 0); Week 2; Week 4; Week 12
|
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
|
|
T regulatory cell (Treg) suppression assay
時間枠：Baseline visit (week 0); Week 4
|
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
|
|
Single cell RNA sequencing of immune cells
時間枠：Baseline visit (week 0); Week 4
|
Analysis of the transcriptome of immune cells using cellular indexing of transcriptomes and epitopes (CITEseq) |
Baseline visit (week 0); Week 4
|
|
Intestinal barrier function
時間枠：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
|
|
Taxonomy of the fecal microbiome
時間枠：Baseline visit (week 0); Week 4
|
The taxonomy of the fecal microbiome will be anayzed using 16S RNA amplicon sequencing. |
Baseline visit (week 0); Week 4
|
|
Cardiovascular Phenotyping
時間枠：Baseline visit (week 0); Week 2; Week 4; Week 12
|
Analysis of heart rate over time. |
Baseline visit (week 0); Week 2; Week 4; Week 12
|
|
Cardiovascular Phenotyping
時間枠：Baseline visit (week 0); Week 2; Week 4; Week 12
|
Analysis of blood pressure over time. |
Baseline visit (week 0); Week 2; Week 4; Week 12
|
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Cholesterol levels
時間枠：Baseline visit (week 0); Week 2; Week 4; Week 12
|
Cholesterol levels will be assessed using standard clinical lab values. |
Baseline visit (week 0); Week 2; Week 4; Week 12
|
協力者と研究者
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- EA2/195/22
医薬品およびデバイス情報、研究文書
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米国FDA規制機器製品の研究
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。