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

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 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.

Conditions

• Critical Illness
• Fasting State
• Ketosis
• Nutrition

Interventions

OTHER

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).

OTHER

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.

OTHER

Fasting

72-hour fasting period with water and non-caloric beverages.

Sponsors & Collaborators

• Tartu University Hospital

  collaborator OTHER

• Karolinska University Hospital

  lead OTHER

Principal Investigators

• Martin Sundström Rehal, MD PhD · Karolinska University Hospital/Karolinska Institutet

• Olav Rooyackers, PhD · Karolinska University Hospital/Karolinska Institute

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2026-08-31

Primary Completion

2027-07-31

Completion

2027-07-31

Countries

• Sweden

Study Locations