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

Sponsor
Aarhus University Hospital (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05074862
Collaborator
(none)
10
Enrollment
1
Location
2
Arms
16
Anticipated Duration (Months)
0.6
Patients Per Site Per Month

Study Details

Study Description

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
  • Dietary Supplement: KetoneAid KE4 Pro Monoester
  • Dietary Supplement: Maltodextrin and fat-based placebo
 Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
10 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Intervention Model Description:
A randomized double-blind isocaloric placebo-controlled cross-over study.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.
Anticipated Study Start Date :
Aug 1, 2022
Anticipated Primary Completion Date :
Jun 1, 2023
Anticipated Study Completion Date :
Dec 1, 2023

Arms and Interventions

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

Primary Outcome Measures

  1. Net leg phenylalanine release [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. [3 hours.]

  2. Change in rate of disappearance of phenylalanine over the leg. [3 hours.]

  3. Whole body palmitate flux [3 hours.]

    As measured by rate of appearance of a palmitate-tracer

  4. Change in arterial pH. [3 hours.]

  5. Changes in inflammatory cytokines (IL-1, IL-6, IL-18, TNFa) [3 hours.]

  6. Changes in intramyocellular protein metabolic signalling pathways. [3 hours.]

    The Akt-, mTor-, and ubiquitin-proteasome pathways.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Locations

Site City State Country Postal Code
1 Aarhus University Hospital Aarhus Denmark DK-8200

Sponsors and Collaborators

  • Aarhus University Hospital

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
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:
Oct 12, 2021
Last Update Posted:
Jun 7, 2022
Last Verified:
Jun 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Critical Illness

Study Results

No Results Posted as of Jun 7, 2022