Critical IllnessKETO-FASTNCT07738536
Ketosis, Immune Function and Metabolic Adaptation in Response to Short-term Fasting in Critical Illness
A study testing Delayed nutrition, Standard nutrition and Fasting in people with Critical Illness and Fasting State, run by Karolinska University Hospital at 1 site in Sweden.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Critical Illness, Fasting State, Ketosis
- What is being tested?
- Delayed nutrition, Standard nutrition and Fasting
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteSweden
- Study dates
- 31 Aug 2026to 31 Jul 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Adult (≥18 years).
- ICU admission (index admission to the participating ICU).
Who cannot join
- 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),
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Sweden1 site
Karolinska University Hospital Huddinge
Stockholm, 14186
Martin Sundström Rehal, MD PhD, +46812381507, martin.sundstrom-rehal@regionstockholm.se
About this study
Official title: 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.
Read the detailed description
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.
- Conditions
- Critical Illness, Fasting State, Ketosis, Nutrition
- Being tested
- Delayed nutrition, Standard nutrition, Fasting
- Keywords
- Critical Care, Intensive care, Fasting, Ketosis, Calorie restriction
- Medical subject headings
- Critical Illness, Ketosis, Fasting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Delayed nutritionOther
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).
Standard nutritionOther
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.
FastingOther
72-hour fasting period with water and non-caloric beverages.
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | 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. Receives: Other: Delayed nutrition |
| Control | Active comparator | Intensive care unit patients with policy allocation to standard care in main study: nutritional management according to regular unit protocols. Receives: Other: Standard nutrition |
| Healthy reference controls | Active comparator | Healthy subjects undergoing 72 hour fast with same blood sampling procedure as in ICU. Receives: Other: Fasting |
What is being measured
The primary outcome is the main question the study is designed to answer.
Between-group differences over time in plasma β-hydroxybutyrate and acetoacetate concentrations during the first 72 hours after ICU admission
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.
Measured: From ICU admission and up to 72 hours after ICU admission, using serial daily blood samples
Secondary outcomes (6)
Between-group difference in serum-induced autophagy flux in cultured cells
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.
Measured: Single serum 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
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.
Measured: 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
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.
Measured: From ICU admission and up to 72 hours after ICU admission, using serial daily blood samples
Between-group difference in normalized relative abundance of autophagy-related proteins in peripheral blood leukocytes assessed by Western blotting
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.
Measured: 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
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.
Measured: 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
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.
Measured: Single final substudy sample collected on ICU day 3 or 4, depending on the time of ICU admission
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2026
- Study start31 Aug 2026 (estimated)
- Primary completion31 Jul 2027 (estimated)
- Study completion31 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Critical IllnessStudies of the same condition, open and under way.
- More trials run by Karolinska University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Cluster randomized cross-over clinical trial.
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Karolinska University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Tartu University Hospital
- Responsible party
- Principal investigator, Martin Sundstrom Rehal, Karolinska University Hospital
- Investigators
- Martin Sundström Rehal, MD PhD, Principal investigator, Karolinska University Hospital/Karolinska InstitutetOlav Rooyackers, PhD, Study chair, Karolinska University Hospital/Karolinska Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07738536
- Sponsor's protocol ID
- K 2026-5194
- Other IDs
- ISRCTN16339579
- Acronym
- KETO-FAST
- Status last verified
- Aug 2026
- First submitted
- 13 Jul 2026
- Last updated
- 1 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data may be made available after publication of the main substudy results upon reasonable request and according to applicable ethical approvals, data protection regulations, biobanking regulations, and material transfer agreements. Omics data sharing will be governed by participant consent, ethical approval, and applicable data protection requirements.
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT07738536
- Acronym / sponsor ID
- KETO-FAST / K 2026-5194
- Conditions
- Critical Illness, Fasting State, Ketosis, Nutrition
- Keywords
- Critical Care, Intensive care, Fasting, Ketosis, Calorie restriction
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Karolinska University HospitalUniversity, hospital or other
- Collaborators
- Tartu University Hospital
- Study start
- 31 Aug 2026 (estimated)
- Primary completion
- 31 Jul 2027 (estimated)
- Study completion
- 31 Jul 2027 (estimated)
- First posted
- 31 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Cluster randomized cross-over clinical trial.
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Other: Delayed nutritionIntensive 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. |
| Control | Active comparator | Other: Standard nutritionIntensive care unit patients with policy allocation to standard care in main study: nutritional management according to regular unit protocols. |
| Healthy reference controls | Active comparator | Other: FastingHealthy subjects undergoing 72 hour fast with same blood sampling procedure as in ICU. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Adult (≥18 years).
- ICU admission (index admission to the participating ICU).
Key exclusion criteria (11 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Delayed nutritionIntervention 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). | Other | Intervention |
| Standard nutritionControl 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. | Other | Control |
| Fasting72-hour fasting period with water and non-caloric beverages. | Other | Healthy reference controls |
Primary outcome
Between-group differences over time in plasma β-hydroxybutyrate and acetoacetate concentrations during the first 72 hours after ICU admission
Time frame: 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.
6 secondary outcomes
Between-group difference in serum-induced autophagy flux in cultured cells
Time frame: Single serum 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
Time frame: 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
Time frame: From ICU admission and up to 72 hours after ICU admission, using serial daily blood samples
Between-group difference in normalized relative abundance of autophagy-related proteins in peripheral blood leukocytes assessed by Western blotting
Time frame: 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
Time frame: 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
Time frame: Single final substudy sample collected on ICU day 3 or 4, depending on the time of ICU admission
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2026.
- Individual participant dataSharing planned: Yes. De-identified individual participant data may be made available after publication of the main substudy results upon reasonable request and according to applicable ethical approvals, data protection regulations, biobanking regulations, and material transfer agreements. Omics data sharing will be governed by participant consent, ethical approval, and applicable data protection requirements.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Martin Sundström Rehal, MD PhD principal investigator
Karolinska University Hospital/Karolinska Institutet
Olav Rooyackers, PhD study chair
Karolinska University Hospital/Karolinska Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Delayed nutrition, Standard nutrition and Fasting in people with Critical Illness and Fasting State, run by Karolinska University Hospital at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 1 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Martin Sundström Rehal, MD PhD (+46-8-12381507, martin.sundstrom-rehal@regionstockholm.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Between-group differences over time in plasma β-hydroxybutyrate and acetoacetate concentrations during the first 72 hours after ICU admission (time frame: From ICU admission and up to 72 hours after ICU admission, using serial daily blood samples). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2026.