Intensive Care Unit Acquired WeaknessPhase 2KETO-ICUNCT05074862
Effects of Ketosis on Muscle Kinetics and Signaling During Critical Illness.
A Phase 2 study testing KetoneAid KE4 Pro Monoester in people with Intensive Care Unit Acquired Weakness and Critical Illness, run by Aarhus University Hospital at 1 site in Denmark.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Intensive Care Unit Acquired Weakness, Critical Illness
- What is being tested?
- KetoneAid KE4 Pro Monoester
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Jan 2023to 1 Dec 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
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- Phenylketonuria.
- BMI ≤17 or deemed malnourished as judged by the investigator.
- BMI >40.
Trial locations and contacts
1 site in 1 country.
Niels Møller, Prof. contact
Denmark1 site
Aarhus University Hospital
Aarhus, DK-8200
Kristoffer Berg-Hansen, MD, krisbe@rm.dk
Niels Møller, Prof., niels.moeller@clin.au.dk
About this study
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.
Read more
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.
- Being tested
- KetoneAid KE4 Pro Monoester, Maltodextrin and fat-based placebo
- Medical subject headings
- Critical Illness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetoneAid KE4 Pro MonoesterDietary supplement
A dietary supplement containing ketone monoester.
Maltodextrin and fat-based placeboDietary supplement
Dosis isocaloric to the KetoneAid Arm
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Dietary Supplement: KetoneAid KE4 Pro Monoester |
| Placebo Treatment | Placebo comparator | Maltodextrin- and fatbased placebo in isocaloric, isovolemic dose to the experimental arm. Receives: Dietary Supplement: Maltodextrin and fat-based placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Net leg phenylalanine release
As measured by rate of phenylalanine appearance in relation with the rate of disappearance.
Measured: 3 hours
Secondary outcomes (6)
Change in rate of appearance of phenylalanine over the leg.
Measured: 3 hours.
Change in rate of disappearance of phenylalanine over the leg.
Measured: 3 hours.
Whole body palmitate flux
As measured by rate of appearance of a palmitate-tracer
Measured: 3 hours.
Change in arterial pH.
Measured: 3 hours.
Changes in inflammatory cytokines (IL-1, IL-6, IL-18, TNFa)
Measured: 3 hours.
Changes in intramyocellular protein metabolic signalling pathways.
The Akt-, mTor-, and ubiquitin-proteasome pathways.
Measured: 3 hours.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2021
- Study start1 Jan 2023 (estimated)
- Primary completion1 Jun 2023 (estimated)
- Study completion1 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Intensive Care Unit Acquired WeaknessStudies of the same condition, open and under way.
- More trials run by Aarhus University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- A randomized double-blind isocaloric placebo-controlled cross-over study.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Aarhus University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kristoffer Berg-Hansen, Aarhus University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05074862
- Sponsor's protocol ID
- KETO-ICU 1-10-72-231-21
- Acronym
- KETO-ICU
- Status last verified
- Nov 2022
- First submitted
- 17 Sep 2021
- Last updated
- 4 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Ketosis on Muscle Kinetics and Signaling During Critical Illness.
- ClinicalTrials.gov ID
- NCT05074862
- Acronym / sponsor ID
- KETO-ICU / KETO-ICU 1-10-72-231-21
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Aarhus University HospitalUniversity, hospital or other
- Study start
- 1 Jan 2023 (estimated)
- Primary completion
- 1 Jun 2023 (estimated)
- Study completion
- 1 Dec 2023 (estimated)
- First posted
- 12 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- A randomized double-blind isocaloric placebo-controlled cross-over study.
| Arm | Type | Receives |
|---|---|---|
| Ketone monoester (3-OHB) | Experimental | Dietary Supplement: KetoneAid KE4 Pro MonoesterWeight-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. |
| Placebo Treatment | Placebo comparator | Dietary Supplement: Maltodextrin and fat-based placeboMaltodextrin- and fatbased placebo in isocaloric, isovolemic dose to the experimental arm. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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).
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KetoneAid KE4 Pro MonoesterA dietary supplement containing ketone monoester. | Dietary supplement | Ketone monoester (3-OHB) |
| Maltodextrin and fat-based placeboDosis isocaloric to the KetoneAid Arm | Dietary supplement | Placebo Treatment |
Primary outcome
Net leg phenylalanine release
Time frame: 3 hours
As measured by rate of phenylalanine appearance in relation with the rate of disappearance.
6 secondary outcomes
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.
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Niels Møller, Prof. contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing KetoneAid KE4 Pro Monoester in people with Intensive Care Unit Acquired Weakness and Critical Illness, run by Aarhus University Hospital at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kristoffer Berg-Hansen, MD (60540700, krbhan@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Net leg phenylalanine release (time frame: 3 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2022.