Mechanisms of Insulin Resistance in Critical Illness: Role of Systemic Inflammation and GLP-1
2014年9月19日 更新者：Kirsten Moller、Rigshospitalet, Denmark
The purpose of this study is to determine the role of inflammation and the insulin regulating hormone GLP-1 during critical illness.
調査の概要
詳細な説明
Critically ill patients often exhibit hyperglycaemia. Although the cause of this hyperglycaemia is probably multifactorial, peripheral insulin resistance is a major contributor, similar to type 2 diabetes mellitus (T2D). There are several similarities between critical illness and T2D, including the presence of systemic inflammation and increased plasma free fatty acids (FFA), all of which may induce insulin resistance in healthy volunteers. In critical illness, elevated catecholamines, cortisol, growth hormone and glucagon may also contribute to insulin resistance.
The degree of hyperglycaemia correlates with mortality in ICU patients. van den Berghe et al. found that IV infusion of insulin to obtain strict normoglycaemia reduced mortality as well as morbidity in critically ill surgical patients and in some medical ICU patients.
However, insulin increases the risk of hypoglycaemia; this is a major obstacle to strict euglycaemia in ICU patients and may explain the inability of others to reproduce the benefits reported by van den Berghe et al. Thus, alternatives to insulin for controlling plasma glucose (PG) in ICU patients are warranted.
Aim:
To study the role of the incretin hormone, glucagon-like peptide (GLP)-1 for glycaemic, metabolic, hormonal and inflammatory profile in
- critically ill patients in the intensive care unit (ICU) and
- healthy volunteers exposed to a standardised systemic inflammation
研究の種類
介入
入学 (実際)
40
段階
- 適用できない
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Copenhagen、デンマーク、2100
- Centre of Inflammation and Metabolism - Rigshospitalet 7641
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Copenhagen、デンマーク、2400
- University of Copenhagen
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年～40年 (大人)
健康ボランティアの受け入れ
はい
受講資格のある性別
男
説明
Inclusion Criteria healthy subjects:
- Healthy (assessed by medical history and clinical examination)
- Age 18-40years
- BMI < 30kg/m2
Exclusion Criteria healthy subjects:
- Previous resection of the small intestine (not including the appendix)
- presence of any inflammatory illness during the fortnight preceding the study
Inclusion Criteria critically ill patients:
- Age>18 years
- HbA1C<6,5%
- Admission to the ICU within the last 72 hours
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
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：クロスオーバー割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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プラセボコンパレーター：2C - 1
TNF and OGTT and saline
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Normal saline (NaCl 0,9%)
1000ng/m2 BSA/hour i.v.
infusion for 4-6 hours
Oral glucose tolerance test with 75 g glucose
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アクティブコンパレータ：2C - 2
TNF and OGTT and GLP-1
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1000ng/m2 BSA/hour i.v.
infusion for 4-6 hours
Oral glucose tolerance test with 75 g glucose
GLP-1 1,2pmol/kg/min i.v.
infusion for 4 hours
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プラセボコンパレーター：2C - 3
TNF and IVGTT and saline
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Normal saline (NaCl 0,9%)
1000ng/m2 BSA/hour i.v.
infusion for 4-6 hours
Intravenous glucose tolerance test with infusion of 20% glucose matching the glucose profile of the corresponding OGTT
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アクティブコンパレータ：2C - 4
TNF and IVGTT and GLP-1
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1000ng/m2 BSA/hour i.v.
infusion for 4-6 hours
GLP-1 1,2pmol/kg/min i.v.
infusion for 4 hours
Intravenous glucose tolerance test with infusion of 20% glucose matching the glucose profile of the corresponding OGTT
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プラセボコンパレーター：2A-1
Saline infusion and OGTT
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Normal saline (NaCl 0,9%)
Oral glucose tolerance test with 75 g glucose
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プラセボコンパレーター：2A-2
Saline and IVGTT
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Normal saline (NaCl 0,9%)
Intravenous glucose tolerance test with infusion of 20% glucose matching the glucose profile of the corresponding OGTT
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アクティブコンパレータ：2A-3
TNF and OGTT
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1000ng/m2 BSA/hour i.v.
infusion for 4-6 hours
Oral glucose tolerance test with 75 g glucose
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アクティブコンパレータ：2A-4
TNF and IVGTT
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1000ng/m2 BSA/hour i.v.
infusion for 4-6 hours
Intravenous glucose tolerance test with infusion of 20% glucose matching the glucose profile of the corresponding OGTT
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実験的：1C
OGTT and corresponding IVGTT
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Oral glucose tolerance test with 75 g glucose
Intravenous glucose tolerance test with infusion of 20% glucose matching the glucose profile of the corresponding OGTT
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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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Substudy 2C (12 Healthy volunteers): GLP-1
時間枠：6 weeks after intervention
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Increased plasma insulin and C-peptide (intact insulinotropic effect of GLP-1) during GLP-1 infusion in healthy volunteers.
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6 weeks after intervention
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Substudy 2A (12 Healthy volunteers): Insulin, C-peptide and incretin hormone response
時間枠：6 weeks after intervention
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Insulin, c-peptide and incretin hormone response to glucose stimulation during standardized systemic inflammation (TNF infusion) compared to placebo (saline infusion)
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6 weeks after intervention
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Substudy 1C(8 patients, 8 healthy controls): Insulin, C-peptide and incretin hormone response
時間枠：6 weeks after intervention
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Insulin, c-peptide and incretin hormone response to glucose stimulation during IVGTT compared to OGTT in critically ill patients admitted to the ICU
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6 weeks after intervention
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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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Substudy 2C (12 Healthy volunteers): Clamp
時間枠：6 weeks after intervention
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Enhanced insulin response (AUC) and reduced difference between the AUC obtained during OGTT and IGGTT (reduced endogenous incretin effect) during an isoglycaemic intravenous glucose tolerance test (IVGTT) in healthy volunteers receiving TNF-infusion.
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6 weeks after intervention
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Substudy 2A (12 Healthy volunteers): The incretin effect
時間枠：6 weeks after intervention
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The difference between the plasma insulin AUC obtained during OGTT and IVGTT (endogenous incretin effect).
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6 weeks after intervention
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Substudy 1C (8 patients, 8 healthy controls): The incretin effect
時間枠：6 weeks after intervention
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The difference between the plasma insulin AUC obtained during OGTT and IVGTT (endogenous incretin effect)in non-diabetic critically ill patients admitted to the ICU.
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6 weeks after intervention
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
捜査官
- 主任研究者：Kirsten Møller, MD, Ph.D., DMSc、Centre of Inflammation and Metabolism
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
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研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2011年3月1日
一次修了 (実際)
2014年9月1日
研究の完了 (実際)
2014年9月1日
試験登録日
最初に提出
2011年5月2日
QC基準を満たした最初の提出物
2011年5月3日
最初の投稿 (見積もり)
2011年5月4日
学習記録の更新
投稿された最後の更新 (見積もり)
2014年9月22日
QC基準を満たした最後の更新が送信されました
2014年9月19日
最終確認日
2014年9月1日
詳しくは
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。
Placebo (Saline)の臨床試験
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