Endogenous Energy Production in Critically Ill Patients

NCT07059988 | Not Yet Recruiting

• 1 other identifier: 2024-9306
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to investigate when critically ill patients transition from a non-suppressible catabolism to a normal response to feeding. Endogenous production of glucose, fat and protein will be studied on a minimum of two occasions in mechanically ventilated ICU patients, in a fasted state and during parenteral nutrition. Substrate kinetics are estimated by a tracer dilution method using infusions of isotopically labeled glucose, glycerol and phenylalanine. Blood sampling for metabolomics analysis will be performed to elucidate potential biomarkers indicating an anabolic response to nutrition.

Conditions

Critical Illness; Metabolism and Nutrition Disorder

Outcome Measures

Primary Outcomes (3)

• Attenuation of glucose production in response to nutrition in early acute phase in ICU.

  Difference in endogenous rate of appearance of glucose, calculated from enrichment of labelled substrates in plasma of glucose between the fasted and fed state in the early acute phase in ICU.

  Early acute phase of critical illness, i.e., 24-72 hours after ICU admission. The difference between substrate kinetics at 165-180 min and 345-360 min after the start of the tracer infusion will be calculated.

• Attenuation of phenylalanine production in response to nutrition in early acute phase in ICU.

  Difference in endogenous rate of appearance of phenylalanine, calculated from enrichment of labelled substrates in plasma of phenylalanine, between the fasted and fed states in the early acute phase in ICU.

  Early acute phase of critical illness, i.e., 24-72 hours after ICU admission. The difference between substrate kinetics at 165-180 min and 345-360 min after the start of the tracer infusion will be calculated.

• Attenuation of glycerol production in response to nutrition in early acute phase in ICU.

  Difference in endogenous rate of appearance of glycerol, calculated from enrichment of labelled substrates in plasma of glycerol, between the fasted and fed states in the early acute phase in ICU.

  Early acute phase of critical illness, i.e., 24-72 hours after ICU admission. The difference between substrate kinetics at 165-180 min and 345-360 min after the start of the tracer infusion will be calculated.

Secondary Outcomes (9)

• Attenuation of glucose production in response to nutrition in the late acute phase compared to the early acute phase in the ICU.

  The early acute phase is between 24 and 72 hours after ICU admission, and the late acute phase between 120 and 148 hours, i.e., 5-7 days after ICU admission.

• Attenuation of glycerol production in response to nutrition in the late acute phase compared to the early acute phase in the ICU.

  The early acute phase is between 24 and 72 hours after ICU admission, and the late acute phase between 120 and 148 hours, i.e., 5-7 days after ICU admission.

• Attenuation of phenylalanine production in response to nutrition in the late acute phase compared to the early acute phase in the ICU.

  The early acute phase is between 24 and 72 hours after ICU admission, and the late acute phase between 120 and 148 hours, i.e., 5-7 days after ICU admission.

• Attenuation of glucose production in response to nutrition in the early acute phase in the ICU compared to healthy controls.

  Early acute phase of critical illness, i.e., 24-72 hours after ICU admission. The difference between substrate kinetics at 165-180 min and 345-360 min after the start of the tracer infusion will be calculated.

• Attenuation of glycerol production in response to nutrition in the early acute phase in the ICU compared to healthy controls.

  Early acute phase of critical illness, i.e., 24-72 hours after ICU admission. The difference between substrate kinetics at 165-180 min and 345-360 min after the start of the tracer infusion will be calculated.

Other Outcomes (13)

• Metabolomics

  The early acute phase is between 24 and 72 hours after ICU admission, and the late acute phase is between 120 and 148 hours, i.e., 5-7 days after ICU admission.

• Attenuation of glucose production in response to nutrition in the late phase compared to the early acute phase in the ICU.

  The early acute phase is between 24 and 72 hours after ICU admission, and the late acute phase is more than 240 hours, i.e., 10 days after ICU admission.

• Attenuation of glycerol production in response to nutrition in the late phase compared to the early acute phase in the ICU.

  The early acute phase is between 24 and 72 hours after ICU admission, and the late acute phase is more than 240 hours, i.e., 10 days after ICU admission.

Study Arms (2)

ICU Patients

EXPERIMENTAL

Mechanically ventilated patients admitted to the study site ICU.

Other: Stable isotope tracers; Dietary Supplement: Parenteral nutrition

Control group

EXPERIMENTAL

Non-hospitalized study subjects recruited through public advertising at the study site, age-matched on group level.

Other: Stable isotope tracers; Dietary Supplement: Parenteral nutrition

Interventions

Stable isotope tracers OTHER

Deuterium-labelled non-radioactive stable isotopes of glucose, phenylalanine and glycerol.

Control group; ICU Patients

Parenteral nutrition DIETARY_SUPPLEMENT

Parenteral nutrition infused a rate corresponding to 100% of measured energy expenditure, started after blood sampling during a baseline fasting period.

Control group; ICU Patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For the ICU group:
• ≥18 years old and admitted to the ICU
• Invasive mechanical ventilation
• Arterial and central line in situ
• Expected to remain in ICU \>72 hours
• For the control group:
• \. ≥18 years old

You may not qualify if:

• Lack of informed consent by patient/next of kin
• Liver transplant
• Acute or acute on chronic liver failure
• Cirrhosis
• Known diabetes mellitus
• Pancreatic surgery
• Acute or chronic pancreatitis
• Pregnancy
• Intubated only for airway protection or neurologic deficit
• Mitochondrial disease
• Disorder of amino acid metabolism
• Familial hypertriglyceridemia
• Severe acquired hypertriglyceridemia (≥10 mmol/L)
• Requiring ongoing large volume resuscitation of crystalloids or blood products
• \>72 hours in ICU before enrollment

Sponsors & Collaborators

• Karolinska University Hospital: lead

Study Sites (1)

Karolinska University Hospital Huddinge

Stockholm, 14186, Sweden

Location

MeSH Terms

Conditions

Critical Illness; Nutrition Disorders

Interventions

Parenteral Nutrition

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Feeding Methods; Therapeutics; Nutritional Support; Nutrition Therapy

Study Officials

• Olav Rooyackers, PhD

  Karolinska University Hospital/Karolinska Institute

  STUDY CHAIR

• Martin Sundström Rehal, MD PhD

  Karolinska University Hospital/Karolinska Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Martin Sundström Rehal, MD PhD

CONTACT

+46812381507; martin.sundstrom-rehal@regionstockholm.se

Timo Oosterveld, MD

CONTACT

0046701466533; timo.oosterveld@ki.se

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Patients and age-matched controls.

Study Record Dates

• First Submitted: June 23, 2025
• First Posted: July 11, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): May 1, 2027
• Last Updated: July 11, 2025

Record last verified: 2025-07

Locations

SE (1)