此页面是自动翻译的，不保证翻译的准确性。请参阅英文版对于源文本。

Ketosis, Immune Function and Metabolic Adaptation in Response to Short-term Fasting in Critical Illness (KETO-FAST)

2026年8月28日更新者：Martin Sundstrom Rehal、Karolinska University Hospital

KETOsis, Immune Function and Metabolic Adaptation in Response to Short-Term Fasting in Critical Illness (KETO-FAST): A Translational Substudy of the FAST-ICU Cluster-randomized Cross-over Trial.

KETO-FAST is a pre-planned translational substudy of the FAST-ICU cluster-randomized cross-over trial. The substudy will characterize ketone body production and associated metabolic, autophagy-related, and immune cellular responses during the first 72 hours after intensive care unit admission in critically ill patients exposed to delayed nutrition compared with patients receiving standard care.

Patients enrolled in FAST-ICU at designated participating centers will undergo serial blood sampling during the first 72 hours after ICU admission. Plasma ketone body concentrations, targeted metabolomics, serum-induced cellular responses in vitro, leukocyte autophagy markers, and immune cell phenotypes and functional markers will be assessed. In addition, 10 healthy volunteers will perform a 72-hour fast with blood sampling to provide reference values from non-critically ill subjects.

研究概览

地位

尚未招聘

条件

干预/治疗

详细说明

Early nutrition during critical illness remains controversial. Large randomized trials in intensive care unit patients have found no clear benefit and possible harm from full early feeding, while current guidelines recommend early hypocaloric nutrition. However, high-quality evidence comparing early hypocaloric nutrition with complete withholding of nutrition during the first days of critical illness is limited.

In healthy humans, short-term starvation induces ketone body production through fatty acid oxidation. Ketone bodies such as β-hydroxybutyrate and acetoacetate are energy substrates for organs including the heart and brain and may also act as signaling molecules involved in autophagy, mitochondrial metabolism, and immune function. In critical illness, however, the normal fasting response may be altered by stress metabolism, inflammation, insulin administration, corticosteroids, and organ dysfunction. The extent to which critically ill patients develop clinically relevant ketosis during short-term fasting remains uncertain.

The parent FAST-ICU trial is a cluster-randomized cross-over trial comparing two ICU nutrition strategies during the first 72 hours after ICU admission: delayed nutrition with no enteral or parenteral nutrition and no glucose-containing maintenance fluids, versus standard care including early enteral nutrition and maintenance glucose according to local practice. KETO-FAST uses this randomized exposure to study the biological response to short-term fasting in critically ill patients.

The primary objective of KETO-FAST is to compare plasma ketone body concentrations during the first 72 hours after ICU admission between patients exposed to delayed nutrition and patients receiving standard care. Secondary and exploratory objectives are to characterize associated changes in targeted metabolic pathways, serum-mediated cellular responses, leukocyte autophagy markers, and immune cell phenotypes and functional markers.

研究类型

介入性

注册 (估计的)

200

阶段

不适用

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习联系方式

姓名：Martin Sundström Rehal, MD PhD
电话号码：+46-8-12381507
邮箱：martin.sundstrom-rehal@regionstockholm.se

学习地点

瑞典
- - Stockholm、瑞典、14186
    - Karolinska University Hospital Huddinge
    - 接触：
      
      Martin Sundström Rehal, MD PhD
      
      电话号码：+46812381507
      
      邮箱：martin.sundstrom-rehal@regionstockholm.se

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

成人
年长者

接受健康志愿者

是的

描述

Inclusion Criteria:

Adult (≥18 years).
ICU admission (index admission to the participating ICU).

Exclusion Criteria:

The patient requires intravenous glucose infusion, enteral nutrition or parenteral nutrition according to the attending clinician's assessment,
Acute or acute-on-chronic liver failure
Moderate hypernatremia ( >150 mmol/L)
Diabetic ketoacidosis or hyperosmolar hyperglycemic state at admission,
Pregnancy,
Exclusive end-of-life care (no other treatment goal than comfort care for end of life),
Organ donor,
Prior enrolment in this trial during the same hospitalisation,
Patients with a metabolic disease requiring specific diet and patients with clinical need for a ketogenic diet.
Patients already enrolled in other interventional studies on nutrition, intravenous fluids, phosphate supplementation or hormonal therapies that influence glucose homeostasis.
Inclusion not possible due to site-specific regulatory issues regarding the ethical approval or informed consent procedure.

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

主要用途：治疗
分配：随机化
介入模型：交叉作业
屏蔽：无（打开标签）

手臂数量

武器和干预

参与者组/臂	干预/治疗
实验性的：Intervention Intensive care unit patients with policy allocation to delayed medical nutrition therapy in main study: no enteral nutrition, parenteral nutrition or maintenance glucose solutions for first 72 hours.	其他：Delayed nutrition Intervention Policy (A): Withhold nutrition and glucose solutions (First 72 h) No enteral nutrition (EN) and no parenteral nutrition (PN) for the first 72 hours from ICU admission time (t=0). No glucose-containing maintenance IV solutions during the first 72 hours. Balanced crystalloids or normal saline permitted per clinical need. 5% glucose solution permitted as vehicle for IV medications as necessary (according to local standard), or as treatment for hypernatremia Oral intake permitted ad lib if the patient is awake, willing and able to eat safely. Micronutrients: daily vitamins and trace elements are allowed per local practice. Protein supplements are not allowed unless part of the standard oral diet. Arterial or venous blood glucose measurement every 4h. Rescue glucose will be administered according to local protocol. After 72 hours, feeding transitions to usual care at clinician discretion (including EN/PN initiation and caloric/protein targets).
有源比较器：Control Intensive care unit patients with policy allocation to standard care in main study: nutritional management according to regular unit protocols.	其他：Standard nutrition Control Policy (B): Standard of Care Initiation and advancement of EN/PN and use of glucose-containing maintenance fluids per local practice from admission. Arterial or venous blood glucose measurement every 4h. Insulin and glycaemic control per local protocols.
有源比较器：Healthy reference controls Healthy subjects undergoing 72 hour fast with same blood sampling procedure as in ICU.	其他：Fasting 72-hour fasting period with water and non-caloric beverages.

研究衡量的是什么？

主要结果指标

结果测量	措施说明	大体时间
Between-group differences over time in plasma β-hydroxybutyrate and acetoacetate concentrations during the first 72 hours after ICU admission 大体时间：From ICU admission and up to 72 hours after ICU admission, using serial daily blood samples	Plasma β-hydroxybutyrate and acetoacetate concentrations will be measured in mmol/L in serial blood samples collected from ICU admission through 72 hours after admission. Cumulative concentrations of ketone bodies will be compared between the delayed-nutrition and standard-care groups over the measurement period. Results will be reported as between-group effect estimates over time, with 95% confidence intervals.	From ICU admission and up to 72 hours after ICU admission, using serial daily blood samples

次要结果测量

结果测量	措施说明	大体时间
Between-group difference in serum-induced autophagy flux in cultured cells 大体时间：Single serum sample collected on ICU day 3 or 4, depending on the time of ICU admission	Cultured cells will be incubated with serum collected from substudy participants. Autophagy flux will be quantified using prespecified cellular autophagy markers under paired conditions with and without pharmacological inhibition of lysosomal degradation. The resulting normalized autophagy-flux measure will be compared between the delayed-nutrition and standard-care groups and reported as a between-group effect estimate with a 95% confidence interval.	Single serum sample collected on ICU day 3 or 4, depending on the time of ICU admission
Between-group difference in normalized relative abundance of autophagy-related proteins in peripheral blood leukocytes assessed by Western blotting 大体时间：Single final substudy sample collected on ICU day 3 or 4, depending on the time of ICU admission	The relative abundance of prespecified autophagy-related proteins will be quantified in isolated peripheral blood leukocytes by Western blot densitometry and normalized to an appropriate loading control. For each protein marker, and for derived protein ratios where applicable, normalized values will be compared between the randomized groups and reported as a between-group effect estimate with a 95% confidence interval.	Single final substudy sample collected on ICU day 3 or 4, depending on the time of ICU admission
Between-group differences in frequencies of major peripheral blood immune-cell subsets assessed by multiparameter flow cytometry 大体时间：Single final substudy sample collected on ICU day 3 or 4, depending on the time of ICU admission	Multiparameter flow cytometry will be used to identify and quantify prespecified major immune-cell populations and phenotypic subsets relevant to critical illness and nutrient deprivation. Each subset will primarily be expressed as a percentage of its relevant parent cell population. Subset frequencies will be compared between the delayed-nutrition and standard-care groups and reported as between-group effect estimates with 95% confidence intervals.	Single final substudy sample collected on ICU day 3 or 4, depending on the time of ICU admission
Between-group differences in immune-cell phenotypes and marker expression assessed by multiparameter flow cytometry 大体时间：Single final substudy sample collected on ICU day 3 or 4, depending on the time of ICU admission	Prespecified peripheral blood immune-cell populations will be characterized by multiparameter flow cytometry. Outcomes will include the frequency of cell populations expressing markers related to immune activation, exhaustion or immune-checkpoint signalling, cellular metabolic state, and functional capacity, together with marker-expression intensity where applicable. Results for each prespecified cell population and marker will be compared between the delayed-nutrition and standard-care groups and reported as between-group effect estimates with 95% confidence intervals.	Single final substudy sample collected on ICU day 3 or 4, depending on the time of ICU admission
Between-group difference in normalized expression of prespecified autophagy-related genes in peripheral whole blood on ICU day 3 or 4, assessed by RNA sequencing 大体时间：Single blood sample collected on ICU day 3 or 4, depending on the time of ICU admission	RNA will be extracted from peripheral whole blood collected in EDTA tubes on ICU day 3 or 4. Expression of prespecified autophagy-related genes will be quantified using RNA sequencing and compared between the randomized groups. For each gene, the treatment effect will be reported as the between-group log2 fold change with a 95% confidence interval and a false-discovery-rate-adjusted P value.	Single blood sample collected on ICU day 3 or 4, depending on the time of ICU admission
Between-group differences in plasma concentrations of prespecified metabolites and pathway-level metabolomic measures during the first 72 hours after ICU admission 大体时间：From ICU admission and up to 72 hours after ICU admission, using serial daily blood samples	Targeted metabolomic analysis will quantify prespecified plasma metabolites related to metabolic pathways relevant to fasting and critical illness, including ketogenesis, fatty acid metabolism, amino acid metabolism, glycolysis, and the tricarboxylic acid cycle. Individual metabolite concentrations and predefined pathway-level summary measures, where applicable, will be compared between the delayed-nutrition and standard-care groups across the first 72 hours after ICU admission. Results will be reported as between-group effect estimates with 95% confidence intervals.	From ICU admission and up to 72 hours after ICU admission, using serial daily blood samples

其他结果措施

结果测量	措施说明	大体时间
Between-group differences in point-of-care whole-blood β-hydroxybutyrate concentration during the first 72 hours after ICU admission 大体时间：From ICU admission and up to 72 hours after ICU admission, using serial daily blood samples	Whole-blood β-hydroxybutyrate concentration will be measured in mmol/L using a point-of-care ketone analyzer at participating sites where this measurement is available. Measurements obtained from ICU admission through 72 hours will be compared between the delayed-nutrition and standard-care groups. Results will be reported for individual sampling time points and as an overall between-group effect across the measurement period, with 95% confidence intervals.	From ICU admission and up to 72 hours after ICU admission, using serial daily blood samples

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Karolinska University Hospital

合作者

Tartu University Hospital

调查人员

学习椅：Olav Rooyackers, PhD、Karolinska University Hospital/Karolinska Institute
首席研究员：Martin Sundström Rehal, MD PhD、Karolinska University Hospital/Karolinska Institutet

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (估计的)

2026年8月31日

初级完成 (估计的)

2027年7月31日

研究完成 (估计的)

2027年7月31日

研究注册日期

首次提交

2026年7月13日

首先提交符合 QC 标准的

2026年7月29日

首次发布 (实际的)

2026年7月31日

研究记录更新

最后更新发布 (实际的)

2026年9月1日

上次提交的符合 QC 标准的更新

2026年8月28日

最后验证

2026年8月1日

Ketosis, Immune Function and Metabolic Adaptation in Response to Short-term Fasting in Critical Illness (KETO-FAST)