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

NCT05074862 | Unknown Phase 2

• 1 other identifier: KETO-ICU 1-10-72-231-21
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Net leg phenylalanine release

  As measured by rate of phenylalanine appearance in relation with the rate of disappearance.

  3 hours

Secondary Outcomes (6)

• Change in rate of appearance of phenylalanine over the leg.

  3 hours.

• Change in rate of disappearance of phenylalanine over the leg.

  3 hours.

• Whole body palmitate flux

  3 hours.

• Change in arterial pH.

  3 hours.

• Changes in inflammatory cytokines (IL-1, IL-6, IL-18, TNFa)

  3 hours.

Study Arms (2)

Ketone monoester (3-OHB)

EXPERIMENTAL

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.

Dietary Supplement: KetoneAid KE4 Pro Monoester

Placebo Treatment

PLACEBO COMPARATOR

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

Dietary Supplement: Maltodextrin and fat-based placebo

Interventions

KetoneAid KE4 Pro Monoester DIETARY_SUPPLEMENT

A dietary supplement containing ketone monoester.

Ketone monoester (3-OHB)

Maltodextrin and fat-based placebo DIETARY_SUPPLEMENT

Dosis isocaloric to the KetoneAid Arm

Placebo Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Aarhus University Hospital: lead

Study Sites (1)

Aarhus University Hospital

Aarhus, DK-8200, Denmark

Location

MeSH Terms

Conditions

Critical Illness

Interventions

maltodextrin

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Kristoffer Berg-Hansen, MD

CONTACT

60540700; krbhan@gmail.com

Niels Møller, Prof.

CONTACT

niels.moeller@clin.au.dk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Principal Investigator

Model Details: A randomized double-blind isocaloric placebo-controlled cross-over study.

Study Record Dates

• First Submitted: September 17, 2021
• First Posted: October 12, 2021
• Study Start: January 1, 2023
• Primary Completion: June 1, 2023
• Study Completion: December 1, 2023
• Last Updated: November 4, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)