Methionine Metabolism in Parenterally Fed Pediatric Sepsis
Methionine Metabolism in Parenterally Fed Critically Ill Children
Critically ill children have abnormal utilization of nutrients such as glucose, lipids and protein. Protein synthesis is increased mainly in the form of immune and signaling proteins, while synthesis of muscle and structural proteins is decreased. The metabolism of sulfur amino acids and specifically methionine and cysteine have not been investigated in critically ill septic children, despite that sulfur amino acids have important roles on thiol, antioxidant and epigenetic reactions, as well as precursor of glutathione (GSH). Methionine metabolism in critically ill children will be influenced by its rate of utilization through the transmethylation, remethylation and transsulfuration pathways, which are the major pathways of methionine metabolism.
The investigators study aims to investigate the metabolism of methionine and cysteine in parenterally fed critically ill septic children. The investigators aim to determine the rates of transmethylation, remethylation, transsulfuration and GSH synthesis rates in critically ill septic children, to determine in vivo, whole body sulfur amino acid metabolism when sulfur amino acids are supplied by the parenteral route. The objective is to determine whether current parenteral intakes support GSH synthesis and if methionine metabolism differs when supplied by the parenteral versus the enteral route. Methionine parenteral requirements will be also studied by using the indicator amino acid oxidation and balance technique.
調査の概要
詳細な説明
This is a prospective, translational study on whole body methionine metabolism and requirements when administered by the parenteral route in critically ill septic children. The study size will include 45 critically ill septic, pediatric patients (15 infants at 1 month-3 years of age, 15 children at 4-12 years of age and 15 adolescent at 13-19 years of age, male and females admitted to the pediatric intensive care unit (PICU) at Children's Medical Center, Dallas. The minimal subject's weight will be 4 kg. The number of subjects includes an expected drop out rate of about 20%, in order to obtain 12 patients with complete data in each group. Patients will receive nutritional support as per standard care. This study will yield important knowledge and may lead in the future to changes in the current practice on the management of critically ill pediatric patients in the PICU.
Study Aim#1: Determine the parenteral requirements of methionine, in the presence of cysteine, in critically ill septic patients' required extended use of TPN, by using the indicator amino acid oxidation and balance technique.
Study Aim#2: Determine methionine metabolism through the rates of transmethylation, transsulfuration and remethylation at the current standard intakes of methionine of 120 mg.kg.d. with negligible amounts of cysteine.
研究の種類
入学 (実際)
連絡先と場所
研究場所
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Ohio
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Cleveland、Ohio、アメリカ、44195
- Cleveland Clinic
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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
サンプリング方法
調査対象母集団
説明
Inclusion Criteria:
- Age 1 month-19 years
Diagnosis of severe sepsis diagnosed as clinical sepsis syndrome (requires two of the following criteria):
- Source of infection
- Fever or Hypothermia
- Leukocytosis or Leucopenia
- Poor organ perfusion (such as delayed capillary refill or decreased urine output or hypotension)
- Bacteremic sepsis demonstrated by positive blood culture
- Weight greater or equal to 4 kg
- Need for parenteral nutrition
- Presence of central and/or arterial venous access as per clinical indication
Exclusion Criteria:
- Patients with metabolic diseases (i.e. Insulin dependent diabetes mellitus, urea cycle disorders, cystinuria, etc.)
- Pregnancy
- Primary liver failure
- Primary renal failure
- Patients on enteral feedings greater than 20% of daily requirement
- Weight less than 4.0 kg
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
- 観測モデル:コホート
- 時間の展望:見込みのある
コホートと介入
グループ/コホート |
介入・治療 |
|---|---|
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重症小児患者
重篤な敗血症の小児患者、生後 1 か月~3 歳、年齢 4~12 歳、および年齢 13~19 歳、男性および女性
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観察的、翻訳的無治療研究
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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 |
|---|---|---|
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Parenteral Requirements of Methionine
時間枠:8 hours
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Breakpoint between the rates of indicator amino acid oxidation and level of parenteral methionine intake.
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8 hours
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Methionine Metabolism
時間枠:8 hours
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Rates of transmethylation, remethylation and transsulfuration and erythrocyte GSH synthesis when nutrients are given by the parenteral route in pediatric critically ill patients.
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8 hours
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協力者と研究者
スポンサー
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
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 (見積もり)
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
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