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

NCT ID: NCT05074862

Last Updated: 2022-11-04

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-01
• Study Completion Date: 2023-12-01

Brief 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.

Conditions

Intensive Care Unit Acquired Weakness; Critical Illness

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Ketone monoester (3-OHB)

Weight-adjusted dose of 3-OHB Monoester (KetoneAID KE4, Virginia, US). Bolus of 300 mg/kg followed by a 2-hour continuous enteral infusion with a dosing of 100 mg/kg/hour (maximal total dose 50 grams). There is a 1-hour lag between the bolus and the continuous infusion.

Group Type: EXPERIMENTAL

KetoneAid KE4 Pro Monoester

Intervention Type: DIETARY_SUPPLEMENT

A dietary supplement containing ketone monoester.

Placebo Treatment

Maltodextrin- and fatbased placebo in isocaloric, isovolemic dose to the experimental arm.

Group Type: PLACEBO_COMPARATOR

Maltodextrin and fat-based placebo

Intervention Type: DIETARY_SUPPLEMENT

Dosis isocaloric to the KetoneAid Arm

Interventions

KetoneAid KE4 Pro Monoester

A dietary supplement containing ketone monoester.

Intervention Type: DIETARY_SUPPLEMENT

Maltodextrin and fat-based placebo

Dosis isocaloric to the KetoneAid Arm

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Aarhus University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Kristoffer Berg-Hansen

MD, Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Aarhus University Hospital

Aarhus, , Denmark

Countries

Denmark

Central Contacts

Kristoffer Berg-Hansen, MD

Role: CONTACT

krbhan@gmail.com

60540700

Niels Møller, Prof.

Role: CONTACT

niels.moeller@clin.au.dk

Facility Contacts

Kristoffer Berg-Hansen, MD

Role: primary

krisbe@rm.dk

Niels Møller, Prof.

Role: backup

niels.moeller@clin.au.dk

Other Identifiers

KETO-ICU 1-10-72-231-21

Identifier Type: -

Identifier Source: org_study_id