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
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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.
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.
A randomized double-blind isocaloric placebo-controlled cross-over study in 10 mechanically ventilated patients with critical illness in the ICU.
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||10 participants|
|Intervention Model:||Crossover Assignment|
|Intervention Model Description:||A randomized double-blind isocaloric placebo-controlled cross-over study.|
|Masking:||Double (Participant, Investigator)|
|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|
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
- Net leg phenylalanine release [ Time Frame: 3 hours ]As measured by rate of phenylalanine appearance in relation with the rate of disappearance.
- Change in rate of appearance of phenylalanine over the leg. [ Time Frame: 3 hours. ]
- Change in rate of disappearance of phenylalanine over the leg. [ Time Frame: 3 hours. ]
- Whole body palmitate flux [ Time Frame: 3 hours. ]As measured by rate of appearance of a palmitate-tracer
- Change in arterial pH. [ Time Frame: 3 hours. ]
- Changes in inflammatory cytokines (IL-1, IL-6, IL-18, TNFa) [ Time Frame: 3 hours. ]
- Changes in intramyocellular protein metabolic signalling pathways. [ Time Frame: 3 hours. ]The Akt-, mTor-, and ubiquitin-proteasome pathways.
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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).
- Moribund or expected withholding treatment within 48 hours as judged by the investigator.
- Palliative goals of care.
- Contraindication for enteral nutrition.
- Known severe musculoskeletal or neurological disability.
- Diabetic ketoacidosis.
- BMI ≤17 or deemed malnourished as judged by the investigator.
- BMI >40.
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
|Contact: Kristoffer Berg-Hansen, MDfirstname.lastname@example.org|
|Contact: Niels Møller, Prof.||email@example.com|
|Aarhus University Hospital|
|Aarhus, Denmark, DK-8200|
|Contact: Kristoffer Berg-Hansen, MD firstname.lastname@example.org|
|Contact: Niels Møller, Prof. email@example.com|
|Responsible Party:||Kristoffer Berg-Hansen, MD, Principal Investigator, Aarhus University Hospital|
|Other Study ID Numbers:||
|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|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||No|