Effects of Ketosis on Muscle Kinetics and Signaling During Critical Illness.

Critical Illness Clinical Trial

— KETO-ICU  

Official title:

Effects of Ketosis on Muscle Kinetics and Signaling During Critical Illness.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05074862
• Other study ID #: KETO-ICU 1-10-72-231-21
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: January 1, 2023
• Est. completion date: December 1, 2023

Study information

• Verified date: November 2022
• Source: University of Aarhus
• Contact: Kristoffer Berg-Hansen, MD
• Phone: 60540700
• Email: krbhan[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Background:

Patients with critical illness in the intensive care unit (ICU) experience marked skeletal muscle weakness, muscle atrophy and disability in physical function, commonly termed ICU-acquired weakness (ICU-AW). The pathophysiology of ICU-AW is complex, but a key feature of skeletal muscle wasting is disturbed protein metabolism reflected in both increased rate of muscle protein degradation and reduced synthesis. Treatment with 3-OHB seems a promising new anticatabolic treatment in patients with critical illness, preventing ICU-AW. To date, no data exist on the clinical and functional effects of ketone body modulation in patients with critical illness.

Objective:

The aim to investigate the effect of exogenous 3-OHB administration on muscle protein kinetics and lipolysis in patients with critical illness, aiming towards preventing ICU-AW.

Design:

A randomized double-blind isocaloric placebo-controlled cross-over study in 10 mechanically ventilated patients with critical illness in the ICU.

Methods:

Evaluation of whole-body and focal leg protein kinetics using labeled phenylalanine and tyrosine tracers. Assessment of free fatty acid (FFA) turnover using a labeled palmitate tracer. Femoral arterial blood flow (assessed with pulsed-wave Doppler ultrasound) is evaluated once per study period. Blood- and urinary samples are collected routinely throughout the study day. Whenever feasible, muscle and fat biopsies will be taken for analysis of protein and adipocyte metabolic signaling and mitochondrial function.

Perspectives: This investigation may grant essential knowledge on ketosis in critical illness. This may lead to larger clinical trials, and hopefully a new and better treatment strategy aimed at preserving muscle mass and function during and improving recovery after critical illness.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 10
• Est. completion date: December 1, 2023
• Est. primary completion date: June 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Invasive mechanical ventilation via a cuffed endotracheal or tracheotomy tube.

• Expected survival of ICU admission.

• Adults (=18 years).

• Multi-organ failure (Sequential Organ Failure Assessment Score [SOFA] score =2 in 2 or more domains).

Exclusion Criteria:

• Moribund or expected withholding treatment within 48 hours as judged by the investigator.

• Palliative goals of care.

• Contraindication for enteral nutrition.

• Pregnancy.

• Known severe musculoskeletal or neurological disability.

• Diabetic ketoacidosis.

• Phenylketonuria.

• BMI =17 or deemed malnourished as judged by the investigator.

• BMI >40.

Related Conditions & MeSH terms

• Critical Illness
• Intensive Care Unit Acquired Weakness

Intervention

Dietary Supplement:
• KetoneAid KE4 Pro Monoester
A dietary supplement containing ketone monoester.
• Maltodextrin and fat-based placebo
Dosis isocaloric to the KetoneAid Arm

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital	Aarhus

Sponsors (1)

Lead Sponsor	Collaborator
Aarhus University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Net leg phenylalanine release	As measured by rate of phenylalanine appearance in relation with the rate of disappearance.	3 hours
Secondary	Change in rate of appearance of phenylalanine over the leg.		3 hours.
Secondary	Change in rate of disappearance of phenylalanine over the leg.		3 hours.
Secondary	Whole body palmitate flux	As measured by rate of appearance of a palmitate-tracer	3 hours.
Secondary	Change in arterial pH.		3 hours.
Secondary	Changes in inflammatory cytokines (IL-1, IL-6, IL-18, TNFa)		3 hours.
Secondary	Changes in intramyocellular protein metabolic signalling pathways.	The Akt-, mTor-, and ubiquitin-proteasome pathways.	3 hours.