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Effects of Ketosis on Muscle Kinetics and Signaling During Critical Illness. (KETO-ICU)

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ClinicalTrials.gov Identifier: NCT05074862
Recruitment Status : Not yet recruiting
First Posted : October 12, 2021
Last Update Posted : November 4, 2022
Sponsor:
Information provided by (Responsible Party):
Kristoffer Berg-Hansen, Aarhus University Hospital

Study Description
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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.


Condition or disease Intervention/treatment Phase
Intensive Care Unit Acquired Weakness Critical Illness Dietary Supplement: KetoneAid KE4 Pro Monoester Dietary Supplement: Maltodextrin and fat-based placebo Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: A randomized double-blind isocaloric placebo-controlled cross-over study.
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Effects of Ketosis on Muscle Kinetics and Signaling During Critical Illness.
Estimated Study Start Date : January 1, 2023
Estimated Primary Completion Date : June 1, 2023
Estimated Study Completion Date : December 1, 2023
Arms and Interventions
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Arm Intervention/treatment
Experimental: 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.
 Dietary Supplement: KetoneAid KE4 Pro Monoester
A dietary supplement containing ketone monoester.
Placebo Comparator: Placebo Treatment
Maltodextrin- and fatbased placebo in isocaloric, isovolemic dose to the experimental arm.
 Dietary Supplement: Maltodextrin and fat-based placebo
Dosis isocaloric to the KetoneAid Arm


Outcome Measures
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Primary Outcome Measures :
  1. Net leg phenylalanine release [ Time Frame: 3 hours ]
    As measured by rate of phenylalanine appearance in relation with the rate of disappearance.


Secondary Outcome Measures :
  1. Change in rate of appearance of phenylalanine over the leg. [ Time Frame: 3 hours. ]
  2. Change in rate of disappearance of phenylalanine over the leg. [ Time Frame: 3 hours. ]
  3. Whole body palmitate flux [ Time Frame: 3 hours. ]
    As measured by rate of appearance of a palmitate-tracer

  4. Change in arterial pH. [ Time Frame: 3 hours. ]
  5. Changes in inflammatory cytokines (IL-1, IL-6, IL-18, TNFa) [ Time Frame: 3 hours. ]
  6. Changes in intramyocellular protein metabolic signalling pathways. [ Time Frame: 3 hours. ]
    The Akt-, mTor-, and ubiquitin-proteasome pathways.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05074862


Contacts
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Contact: Kristoffer Berg-Hansen, MD 60540700 krbhan@gmail.com
Contact: Niels Møller, Prof. niels.moeller@clin.au.dk

Locations
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Denmark
Aarhus University Hospital
Aarhus, Denmark, DK-8200
Contact: Kristoffer Berg-Hansen, MD       krisbe@rm.dk   
Contact: Niels Møller, Prof.       niels.moeller@clin.au.dk   
Sponsors and Collaborators
Aarhus University Hospital
More Information
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Responsible Party: Kristoffer Berg-Hansen, MD, Principal Investigator, Aarhus University Hospital
ClinicalTrials.gov Identifier: NCT05074862    
Other Study ID Numbers: KETO-ICU 1-10-72-231-21
First Posted: October 12, 2021    Key Record Dates
Last Update Posted: November 4, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Critical Illness
Disease Attributes
Pathologic Processes