Critical IllnessASICSNCT04101071
Alternative Substrates in the Critically Ill Subject
A study testing Modular ketogenic feed and Standard feed in people with Critical Illness, run by Barts & The London NHS Trust at 2 sites in United Kingdom.
Trial summary
The over-arching aim of this study is to investigate the feasibility of administrating alternative substrates to intensive care unit (ICU) patients. This includes reconstituting and administering a modular ketone-inducing (ketogenic) enteral feeding regimen to ICU patients; to show that this feed does increase blood… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Critical Illness
- What is being tested?
- Modular ketogenic feed and Standard feed
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 2 Oct 2019to 27 Apr 2022
- Phase
- Interventional
- 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 years or older
- due to receive enteral nutrition via nasogastric or nasojejunal tube as part of routine care
- mechanically ventilated and likely to remain so for >48 hours
- likely to remain on the ICU for >5 days
- likely to survive for at least 10 days and
- multi-organ failure (Sequential Organ Failure Assessment Score [SOFA] score >2 in 2 or more domains).
Who cannot join
- primary neuromyopathy or significant neurological impairment at the time of ICU admission that would preclude physical activity
- uni- or bilateral lower limb amputation
- requiring sole or supplemental parenteral nutrition
- need for specialist nutritional intervention
- patients with known inborn errors of metabolism
- participation in another clinical trial
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
Bristol Royal Infirmary
Bristol, BS2 8HW
Royal London Hospital
London, E1 1BB
About this study
The over-arching aim of this study is to investigate the feasibility of administrating alternative substrates to intensive care unit (ICU) patients. This includes reconstituting and administering a modular ketone-inducing (ketogenic) enteral feeding regimen to ICU patients; to show that this feed does increase blood ketones; and that it is feasible to collect the desired outcomes. This will allow us to determine in a subsequent randomised controlled trial whether this intervention improves ICU outcomes (including ICU-related muscle loss).
Read the detailed description
Aggressive muscle wasting occurs early in critical illness, and is associated with a greater number of days on a ventilator, increased length of intensive care unit (ICU) and/or hospital stay, and subsequent functional impairment which may last years. Hospital care costs, and ongoing costs of community-based primary healthcare utilisation, are increased. No known interventions prevent this wasting.
Bioenergetic failure in critical illness and the potential for alternative substrate use:
Muscle protein synthesis is highly energy-dependent.The bioenergetic state of the critically-ill patient is compromised leading to decreased Adenosine Tri-Phosphate (ATP) synthesis. Alterations in mitochondrial function have been described repeatedly in the literature which, with other altered cellular processes, impair the utlilisation of metabolic substrates for ATP production.
Carbohydrate utilisation is impaired in critical illness, partly through impaired nuclear-to-membrane translocation of glucose transporter-4 and increased insulin resistance. Hypoxia signalling and inflammation block activity of pyruvate dehydrogenase by upregulation of pyruvate dehydrogenase kinase, increasing glucose availability thus driving pyruvate metabolism to lactate - the Pasteur effect.
The investigator's recently published data suggest that critical illness also impairs mitochondrial oxidation of fatty acids in skeletal muscle, and that the majority of lipids delivered in feed are not utilized for ATP production. This may be of clinical importance, given that lipids contribute 29-43% of the energy content of enteral, and 50% of parenteral, formulae. Lastly, oxidation of amino acids may produce ATP. However, this is not necessarily in the best interest of the patient: these amino acids are then no longer available for muscle protein synthesis. Further, most amino acid oxidation results in pyruvate production and therefore the same issues as those related to carbohydrate metabolism apply. Provision of a new metabolic substrate such as Ketone Bodies (KBs) may address these limitations.
Potential for Muscle Sparing Offered by Ketone Bodies:
During periods of starvation they may provide up to 50% of total body basal energy, enabling the high energy requirement of human brain to be met whilst sparing muscle. Additionally KBs may act as metabolic modulators, improving mitochondrial efficiency (also impaired by critical illness), and reducing reactive oxygen species and free radical formation. They also have anti-inflammatory effects (intramuscular inflammation is a driver of altered protein homeostasis, and anti-apoptotic activity. Together, these additional mechanistic effects may prove useful in ameliorating skeletal muscle wasting. Further, pilot data demonstrate a significant decrease in the plasma concentrations of beta-hydroxybutyrate and acetoacetate in early critical illness, consistent with increased KB uptake and utilisation early in critical illness.
Ketone bodies have diverse extra-mitochondrial metabolic effects. These include immune enhancement functions: specifically, to bacterial infection. Infection and inflammation are drivers of muscle wasting and amelioration of these may impact on this and other outcome measures. Thus, the critically ill patient may benefit from a ketogenic diet which have been used safely in other population groups, including healthy subjects the obese, and in patients with trauma, epilepsy, cardiovascular disease, Type-2 diabetes and Metabolic Diseases.
The objectives/aims are to:
- Show that it is possible to recruit patients to receive a ketogenic feed
- Show that it is possible for researchers to reconstitute the modular ketogenic feed on ICU.
- Show that it is possible to administer ketogenic feed to ICU patients without ill effect.
- Characterise the time-course of ketone generation (and related changes in related metabolic pathways) in response to the ketogenic feed.
- Show that collection of outcome measures relevant for the subsequent substantive study will be feasible.
- Conditions
- Critical Illness
- Being tested
- Modular ketogenic feed, Standard feed
- Keywords
- Critical care, enteral feeding, nasogastric, ketogenic feed, feasibility
- Medical subject headings
- Critical Illness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Modular ketogenic feedOther
Dietician prescribed, and consisting of Betaquik® (from Vitaflo, Nutritional company) to provide medium chain triglycerides), Renapro Shot® (protein), Maxijul® (carbohydrate) and multivitamins according to nutritional need (energy and protein requirements) based on clinical status of the participant. Ketogenic feed to be given continuously via nasogastric tube for 10 days
Standard feedOther
Standard Enteral feed. Dietician prescribed based on clinical status of the participant, as per individual Trust protocols. Standard feed to be given continuously via nasogastric tube for 10 days
| Study group | Role | What they receive |
|---|---|---|
| Modular ketogenic enteral feed | Experimental | Ketogenic enteral feed to be administered continuously for 10 days. Receives: Other: Modular ketogenic feed |
| Standard enteral feed | Active comparator | Standard enteral feed to be administered continuously for 10 days. Receives: Other: Standard feed |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility of patient recruitment; number eligible from screening
Number of patients screened
Measured: 15 months
Feasibility of patient recruitment; percentage eligible from screening
Percentage of patients eligible for recruitment
Measured: 15 months
Feasibility of patient recruitment; number from consent process
Number of eligible patients able to be consented to join the study
Measured: 15 months
Feasibility of patient recruitment: percentage from consent process
Percentage of eligible patients able to be consented to join the study
Measured: 15 months
Feasibility of patient retention during the 10 day study period: number of participants
Number of participants retained for the 10 day study; reasons for withdrawal analysed by descriptive statistics
Measured: 15 months
Feasibility of patient retention during the 10 day study period; percentage of participants
Percentage of participants retained for the 10 day study; reasons for withdrawal analysed by descriptive statistics
Measured: 15 months
Feasibility of provision of ketogenic feed: staff-completed questionnaire
Non-validated questionnaire to be completed by ICU bedside nurses and critical care research nurses within 2 weeks of recruitment completing. 12 questions will ask about ease of reconstituting and using the feed and any side effects encountered. Each question will be scored on a scale of 0-10 with 0 the worst/lowest score and 10 the best/highest score. The results for each question will be presented individually using descriptive statistics as mean +/- standard deviation, with a text description adding any comments received.
Measured: 15 months
Incidence of Adverse Events/Serious Adverse Events, gastric intolerance, glucose variation
Percentage of days event occurred out of total possible days (mean +/- 95% confidence interval): pulmonary aspiration; vomiting, diarrhea (Bristol Stool Score T5-T7), prokinetics use, gastric residual volume >300mls; adverse blood glucose levels of >10.1mmol/l and <3.9mmol/l; Daily insulin use.
Measured: 15 months
Coefficient of Glucose Variation (scored as mean/standard deviation)
Coefficient of Glucose Variation (scored as mean/standard deviation)
Measured: 15 months
Timescale for the development and establishment of ketosis during 10 days of intervention or control feed; beta-hydroxybutyrate
Plasma levels of beta-hydroxybutyrate: mmol/l
Measured: 15 months
Timescale for the development and establishment of ketosis during 10 days of intervention or control feed; acetoacetate
Plasma levels of acetoacetate mmol/l
Measured: 15 months
Timescale for the development and establishment of ketosis during 10 days of intervention or control feed; pyruvate
Plasma levels of pyruvate mmol/l
Measured: 15 months
Timescale for the development and establishment of ketosis during 10 days of intervention or control feed, fat
Plasma levels of fat (ratio of Medium Chain to Long Chain Triglyceride)
Measured: 15 months
Timescale for the development and establishment of ketosis during 10 days of intervention or control feed, glucose
Plasma levels of glucose mmol/l
Measured: 15 months
Timescale for the development and establishment of ketosis during 10 days of intervention or control feed, lactate
Plasma levels of lactate mmol/l
Measured: 15 months
Secondary outcomes (16)
Feasibility of data collection into electronic database from medical notes and nursing sheets as assessed by completion of >80% of available data: blood gases
Arterial Blood Gases, pH, PaO2 and PaCO2 in kPa
Measured: 15 months
Feasibility of data collection into electronic database from medical notes and nursing sheets as assessed by completion of >80% of available data; biochemistry
Bicarbonate, Base Excess, Lactate, other biochemistry data in mmol/l
Measured: 15 months
Feasibility of data collection into electronic database from medical notes and nursing sheets as assessed by completion of >80% of available data; haematology
Hematology data (Hb in g/l, White cell count and platelets in 10 to power of 9/l)
Measured: 15 months
Feasibility of data collection into electronic database from medical notes and nursing sheets as assessed by completion of >80% of available data; bedside physiology
Bedside Physiology (BP, HR, SOFA score, Fluid Balance)
Measured: 15 months
Feasibility of data collection into electronic database from medical notes and nursing sheets as assessed by completion of >80% of available data; nutritional data
Nutritional data (Protein g/kg/day and Energy kcal/kg/day
Measured: 15 months
Feasibility of data collection into electronic database from medical notes and nursing sheets as assessed by completion of >80% of available data; Propofol
Propofol dose (mg/day)
Measured: 15 months
Feasibility of performing quadriceps ultrasound scans: muscle mass
Ultrasound scans of rectus femoris part of quadriceps muscle as a measure of muscle mass
Measured: 15 months
Feasibility of performing functional assessment at hospital discharge by Two- or Six-Minute Walk Test
Two minute or Six-Minute Walk Test (depending on patient capability) captures all the walking distance that a patient can demonstrate (in metres)
Measured: 15 months
Feasibility of performing functional assessment at hospital discharge by Short Physical Performance Battery
Short Physical Performance Battery (scoring between 0-10; includes results of the gait speed, balance tests and chair stand)
Measured: 15 months
Feasibility of performing functional assessment at hospital discharge by CPAx score
Chelsea Critical Care Physical Assessment Score (CPAx): scoring 0-5 in 10 domains
Measured: 15 months
Feasibility of collecting metabolic data on ICU: indirect calorimetry
non-invasive metabolic data via indirect calorimetry on ICU
Measured: 15 months
Feasibility of collecting follow-up data by telephone re quality of life: ED5Q survey
Use of ED5Q survey to determine health-related quality of life; scoring 1-5 in 5 domains, plus 1-100 in 1 domain
Measured: 18 months
Feasibility of collecting follow-up data by telephone re job status: Questions on employment status
Questions on employment status (full-time: yes/no; part-time: yes/no)
Measured: 18 months
Feasibility of collecting follow-up data from medical records: number of GP/nurse visits
Information on health care resource usage from number of GP/nurse visits during 12 months post-ICU and hospital discharge
Measured: 18 months
Biochemical analysis of urine
To determine urinary concentrations of beta-hydroxybutyrate and total nitrogen (in mmol/l)
Measured: 18 months
Biochemical analysis of plasma metabolites, beta-hydroxy butyrate, acetoacetate, leucine, and alanine (all measured in the same Arbitrary Units [AU]).
Investigation into beta-hydroxy butyrate, acetoacetate, leucine, and alanine (all measured in the same Arbitrary Units [AU]) by HPLC; NMR spectra will be phased, baseline corrected, zero filled and referenced prior to multivariate analysis. Multivariate techniques will include principal components analysis (PCA) and prediction and regression using partial least squared discriminant analysis (PLS-DA). Owing to the high variability expected in this data set, orthogonal projection to latent structures (OPLS) will be utilised to maximise the variation in the intervention under study. Given the high number of metabolites expected to be seen, statistical total correlation spectroscopy (STOCSY) will be utilised to detect endogenous responses.
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2019
- Study start2 Oct 2019
- Primary completion27 Apr 2022
- Study completion27 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Critical IllnessStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- SIngle blinded, randomised, controlled feasibility study
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Barts & The London NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol Royal Infirmary, Institute of Child Health
- Responsible party
- Sponsor
- Investigators
- Angela McNelly, PhD, Principal investigator, Royal London Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04101071
- Sponsor's protocol ID
- 266031
- Acronym
- ASICS
- Status last verified
- Mar 2022
- First submitted
- 26 Jun 2019
- Last updated
- 1 Aug 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: (i) Where practicable, publicly funded research data should be made available for access, subject to such conditions as are necessary to ensure compliance with legal, data protection, ethical, confidentiality, intellectual property protection, and security/funder obligations. (ii) The rights of researchers to the exclusive use of research data that they generate as part of a well-defined research project will be protected up until the point of publication or public availability. (iii) Data arising from this research involving human subjects will be anonymised so that it will not be possible to identify any individuals. Where it appears inappropriate to make such data accessible, e.g. it might lead to identification of research subjects or because seeking consent would reduce the rate of participation in the research, the data will remain confidential. (iv) For research collaborations, any open access arrangements can only take place with the agreement of all research partners.
Publications
McNelly A, Langan A, Bear DE, Page A, Martin T, Seidu F, Santos F, Rooney K, Liang K, Heales SJ, Baldwin T, Alldritt I, Crossland H, Atherton PJ, Wilkinson D, Montgomery H, Prowle J, Pearse R, Eaton S, Puthucheary ZA. A pilot study of alternative substrates in the critically Ill subject using a ketogenic feed. Nat Commun. 2023 Dec 15;14(1):8345. doi: 10.1038/s41467-023-42659-8.
PubMed 38102152
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Alternative Substrates in the Critically Ill Subject
- ClinicalTrials.gov ID
- NCT04101071
- Acronym / sponsor ID
- ASICS / 266031
- Conditions
- Critical Illness
- Keywords
- Critical care, enteral feeding, nasogastric, ketogenic feed, feasibility
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Barts & The London NHS TrustUniversity, hospital or other
- Collaborators
- Bristol Royal Infirmary, Institute of Child Health
- Study start
- 2 Oct 2019 (actual)
- Primary completion
- 27 Apr 2022 (actual)
- Study completion
- 27 Apr 2022 (actual)
- First posted
- 24 Sep 2019 (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.
The over-arching aim of this study is to investigate the feasibility of administrating alternative substrates to intensive care unit (ICU) patients. This includes reconstituting and administering a modular ketone-inducing (ketogenic) enteral feeding regimen to ICU patients; to show that this feed does increase blood ketones; and that it is feasible to collect the desired outcomes. This will allow us to determine in a subsequent randomised controlled trial whether this intervention improves ICU outcomes (including ICU-related muscle loss).
Detailed description
Aggressive muscle wasting occurs early in critical illness, and is associated with a greater number of days on a ventilator, increased length of intensive care unit (ICU) and/or hospital stay, and subsequent functional impairment which may last years. Hospital care costs, and ongoing costs of community-based primary healthcare utilisation, are increased. No known interventions prevent this wasting.
Bioenergetic failure in critical illness and the potential for alternative substrate use:
Muscle protein synthesis is highly energy-dependent.The bioenergetic state of the critically-ill patient is compromised leading to decreased Adenosine Tri-Phosphate (ATP) synthesis. Alterations in mitochondrial function have been described repeatedly in the literature which, with other altered cellular processes, impair the utlilisation of metabolic substrates for ATP production.
Carbohydrate utilisation is impaired in critical illness, partly through impaired nuclear-to-membrane translocation of glucose transporter-4 and increased insulin resistance. Hypoxia signalling and inflammation block activity of pyruvate dehydrogenase by upregulation of pyruvate dehydrogenase kinase, increasing glucose availability thus driving pyruvate metabolism to lactate - the Pasteur effect.
The investigator's recently published data suggest that critical illness also impairs mitochondrial oxidation of fatty acids in skeletal muscle, and that the majority of lipids delivered in feed are not utilized for ATP production. This may be of clinical importance, given that lipids contribute 29-43% of the energy content of enteral, and 50% of parenteral, formulae. Lastly, oxidation of amino acids may produce ATP. However, this is not necessarily in the best interest of the patient: these amino acids are then no longer available for muscle protein synthesis. Further, most amino acid oxidation results in pyruvate production and therefore the same issues as those related to carbohydrate metabolism apply. Provision of a new metabolic substrate such as Ketone Bodies (KBs) may address these limitations.
Potential for Muscle Sparing Offered by Ketone Bodies:
During periods of starvation they may provide up to 50% of total body basal energy, enabling the high energy requirement of human brain to be met whilst sparing muscle. Additionally KBs may act as metabolic modulators, improving mitochondrial efficiency (also impaired by critical illness), and reducing reactive oxygen species and free radical formation. They also have anti-inflammatory effects (intramuscular inflammation is a driver of altered protein homeostasis, and anti-apoptotic activity. Together, these additional mechanistic effects may prove useful in ameliorating skeletal muscle wasting. Further, pilot data demonstrate a significant decrease in the plasma concentrations of beta-hydroxybutyrate and acetoacetate in early critical illness, consistent with increased KB uptake and utilisation early in critical illness.
Ketone bodies have diverse extra-mitochondrial metabolic effects. These include immune enhancement functions: specifically, to bacterial infection. Infection and inflammation are drivers of muscle wasting and amelioration of these may impact on this and other outcome measures. Thus, the critically ill patient may benefit from a ketogenic diet which have been used safely in other population groups, including healthy subjects the obese, and in patients with trauma, epilepsy, cardiovascular disease, Type-2 diabetes and Metabolic Diseases.
The objectives/aims are to:
- Show that it is possible to recruit patients to receive a ketogenic feed
- Show that it is possible for researchers to reconstitute the modular ketogenic feed on ICU.
- Show that it is possible to administer ketogenic feed to ICU patients without ill effect.
- Characterise the time-course of ketone generation (and related changes in related metabolic pathways) in response to the ketogenic feed.
- Show that collection of outcome measures relevant for the subsequent substantive study will be feasible.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- SIngle blinded, randomised, controlled feasibility study
| Arm | Type | Receives |
|---|---|---|
| Modular ketogenic enteral feed | Experimental | Other: Modular ketogenic feedKetogenic enteral feed to be administered continuously for 10 days. |
| Standard enteral feed | Active comparator | Other: Standard feedStandard enteral feed to be administered continuously for 10 days. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 18 years or older
- due to receive enteral nutrition via nasogastric or nasojejunal tube as part of routine care
- mechanically ventilated and likely to remain so for >48 hours
- likely to remain on the ICU for >5 days
- likely to survive for at least 10 days and
Key exclusion criteria (6 listed)
- primary neuromyopathy or significant neurological impairment at the time of ICU admission that would preclude physical activity
- uni- or bilateral lower limb amputation
- requiring sole or supplemental parenteral nutrition
- need for specialist nutritional intervention
- patients with known inborn errors of metabolism
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 |
|---|---|---|
| Modular ketogenic feedDietician prescribed, and consisting of Betaquik® (from Vitaflo, Nutritional company) to provide medium chain triglycerides), Renapro Shot® (protein), Maxijul® (carbohydrate) and multivitamins according to nutritional need (energy and protein requirements) based on clinical status of the participant. Ketogenic feed to be given continuously via nasogastric tube for 10 days | Other | Modular ketogenic enteral feed |
| Standard feedStandard Enteral feed. Dietician prescribed based on clinical status of the participant, as per individual Trust protocols. Standard feed to be given continuously via nasogastric tube for 10 days | Other | Standard enteral feed |
Primary outcome
Feasibility of patient recruitment; number eligible from screening
Time frame: 15 months
Number of patients screened
Feasibility of patient recruitment; percentage eligible from screening
Time frame: 15 months
Percentage of patients eligible for recruitment
Feasibility of patient recruitment; number from consent process
Time frame: 15 months
Number of eligible patients able to be consented to join the study
Feasibility of patient recruitment: percentage from consent process
Time frame: 15 months
Percentage of eligible patients able to be consented to join the study
Feasibility of patient retention during the 10 day study period: number of participants
Time frame: 15 months
Number of participants retained for the 10 day study; reasons for withdrawal analysed by descriptive statistics
Feasibility of patient retention during the 10 day study period; percentage of participants
Time frame: 15 months
Percentage of participants retained for the 10 day study; reasons for withdrawal analysed by descriptive statistics
Feasibility of provision of ketogenic feed: staff-completed questionnaire
Time frame: 15 months
Non-validated questionnaire to be completed by ICU bedside nurses and critical care research nurses within 2 weeks of recruitment completing. 12 questions will ask about ease of reconstituting and using the feed and any side effects encountered. Each question will be scored on a scale of 0-10 with 0 the worst/lowest score and 10 the best/highest score. The results for each question will be presented individually using descriptive statistics as mean +/- standard deviation, with a text description adding any comments received.
Incidence of Adverse Events/Serious Adverse Events, gastric intolerance, glucose variation
Time frame: 15 months
Percentage of days event occurred out of total possible days (mean +/- 95% confidence interval): pulmonary aspiration; vomiting, diarrhea (Bristol Stool Score T5-T7), prokinetics use, gastric residual volume >300mls; adverse blood glucose levels of >10.1mmol/l and <3.9mmol/l; Daily insulin use.
Coefficient of Glucose Variation (scored as mean/standard deviation)
Time frame: 15 months
Coefficient of Glucose Variation (scored as mean/standard deviation)
Timescale for the development and establishment of ketosis during 10 days of intervention or control feed; beta-hydroxybutyrate
Time frame: 15 months
Plasma levels of beta-hydroxybutyrate: mmol/l
Timescale for the development and establishment of ketosis during 10 days of intervention or control feed; acetoacetate
Time frame: 15 months
Plasma levels of acetoacetate mmol/l
Timescale for the development and establishment of ketosis during 10 days of intervention or control feed; pyruvate
Time frame: 15 months
Plasma levels of pyruvate mmol/l
Timescale for the development and establishment of ketosis during 10 days of intervention or control feed, fat
Time frame: 15 months
Plasma levels of fat (ratio of Medium Chain to Long Chain Triglyceride)
Timescale for the development and establishment of ketosis during 10 days of intervention or control feed, glucose
Time frame: 15 months
Plasma levels of glucose mmol/l
Timescale for the development and establishment of ketosis during 10 days of intervention or control feed, lactate
Time frame: 15 months
Plasma levels of lactate mmol/l
16 secondary outcomes
Feasibility of data collection into electronic database from medical notes and nursing sheets as assessed by completion of >80% of available data: blood gases
Time frame: 15 months
Feasibility of data collection into electronic database from medical notes and nursing sheets as assessed by completion of >80% of available data; biochemistry
Time frame: 15 months
Feasibility of data collection into electronic database from medical notes and nursing sheets as assessed by completion of >80% of available data; haematology
Time frame: 15 months
Feasibility of data collection into electronic database from medical notes and nursing sheets as assessed by completion of >80% of available data; bedside physiology
Time frame: 15 months
Feasibility of data collection into electronic database from medical notes and nursing sheets as assessed by completion of >80% of available data; nutritional data
Time frame: 15 months
Feasibility of data collection into electronic database from medical notes and nursing sheets as assessed by completion of >80% of available data; Propofol
Time frame: 15 months
Feasibility of performing quadriceps ultrasound scans: muscle mass
Time frame: 15 months
Feasibility of performing functional assessment at hospital discharge by Two- or Six-Minute Walk Test
Time frame: 15 months
Feasibility of performing functional assessment at hospital discharge by Short Physical Performance Battery
Time frame: 15 months
Feasibility of performing functional assessment at hospital discharge by CPAx score
Time frame: 15 months
Feasibility of collecting metabolic data on ICU: indirect calorimetry
Time frame: 15 months
Feasibility of collecting follow-up data by telephone re quality of life: ED5Q survey
Time frame: 18 months
Feasibility of collecting follow-up data by telephone re job status: Questions on employment status
Time frame: 18 months
Feasibility of collecting follow-up data from medical records: number of GP/nurse visits
Time frame: 18 months
Biochemical analysis of urine
Time frame: 18 months
Biochemical analysis of plasma metabolites, beta-hydroxy butyrate, acetoacetate, leucine, and alanine (all measured in the same Arbitrary Units [AU]).
Time frame: 18 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2022.
- Derived from this study: PubMed 38102152McNelly A, Langan A, Bear DE, Page A, Martin T, Seidu F, Santos F, Rooney K, Liang K, Heales SJ, Baldwin T, Alldritt I, Crossland H, Atherton PJ, Wilkinson D, Montgomery H, Prowle J, Pearse R, Eaton S, Puthucheary ZA. A pilot study of alternative substrates in the critically Ill subject using a ketogenic feed. Nat Commun. 2023 Dec 15;14(1):8345. doi: 10.1038/s41467-023-42659-8.
- Individual participant dataSharing planned: Yes. (i) Where practicable, publicly funded research data should be made available for access, subject to such conditions as are necessary to ensure compliance with legal, data protection, ethical, confidentiality, intellectual property protection, and security/funder obligations. (ii) The rights of researchers to the exclusive use of research data that they generate as part of a well-defined research project will be protected up until the point of publication or public availability. (iii) Data arising from this research involving human subjects will be anonymised so that it will not be possible to identify any individuals. Where it appears inappropriate to make such data accessible, e.g. it might lead to identification of research subjects or because seeking consent would reduce the rate of participation in the research, the data will remain confidential. (iv) For research collaborations, any open access arrangements can only take place with the agreement of all research partners.
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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.
Angela McNelly, PhD principal investigator
Royal London Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Modular ketogenic feed and Standard feed in people with Critical Illness, run by Barts & The London NHS Trust at 2 sites in United Kingdom.
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 6 inclusion and 6 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: finished, as of the sponsor's last update on 1 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility of patient recruitment; number eligible from screening (time frame: 15 months). The study lists 15 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04101071, which also lists 1 linked publication.
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 1 Aug 2022.