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Alternative Substrates in the Critically Ill Subject (ASICS)

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ClinicalTrials.gov Identifier: NCT04101071
Recruitment Status : Recruiting
First Posted : September 24, 2019
Last Update Posted : October 8, 2019
Sponsor:
Collaborators:
Bristol Royal Infirmary
Institute of Child Health
Information provided by (Responsible Party):
Barts & The London NHS Trust

Brief 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 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).

Condition or disease Intervention/treatment Phase
Critical Illness Other: Modular ketogenic feed Other: Standard feed Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 37 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: SIngle blinded, randomised, controlled feasibility study
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Other
Official Title: Alternative Substrates in the Critically Ill Subject
Actual Study Start Date : October 2, 2019
Estimated Primary Completion Date : April 15, 2022
Estimated Study Completion Date : October 14, 2023

Arm Intervention/treatment
Experimental: Modular ketogenic enteral feed
Ketogenic enteral feed to be administered continuously for 10 days.
Other: Modular ketogenic feed
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

Active Comparator: Standard enteral feed
Standard enteral feed to be administered continuously for 10 days.
Other: Standard feed
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




Primary Outcome Measures :
  1. Feasibility of patient recruitment; number eligible from screening [ Time Frame: 15 months ]
    Number of patients screened

  2. Feasibility of patient recruitment; percentage eligible from screening [ Time Frame: 15 months ]
    Percentage of patients eligible for recruitment

  3. Feasibility of patient recruitment; number from consent process [ Time Frame: 15 months ]
    Number of eligible patients able to be consented to join the study

  4. Feasibility of patient recruitment: percentage from consent process [ Time Frame: 15 months ]
    Percentage of eligible patients able to be consented to join the study

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. Coefficient of Glucose Variation (scored as mean/standard deviation) [ Time Frame: 15 months ]
    Coefficient of Glucose Variation (scored as mean/standard deviation)

  10. 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

  11. 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

  12. 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

  13. 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)

  14. 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

  15. 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


Secondary Outcome Measures :
  1. 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 ]
    Arterial Blood Gases, pH, PaO2 and PaCO2 in kPa

  2. 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 ]
    Bicarbonate, Base Excess, Lactate, other biochemistry data in mmol/l

  3. 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 ]
    Hematology data (Hb in g/l, White cell count and platelets in 10 to power of 9/l)

  4. 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 ]
    Bedside Physiology (BP, HR, SOFA score, Fluid Balance)

  5. 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 ]
    Nutritional data (Protein g/kg/day and Energy kcal/kg/day

  6. 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 ]
    Propofol dose (mg/day)

  7. Feasibility of performing quadriceps ultrasound scans: muscle mass [ Time Frame: 15 months ]
    Ultrasound scans of rectus femoris part of quadriceps muscle as a measure of muscle mass

  8. Feasibility of performing functional assessment at hospital discharge by Two- or Six-Minute Walk Test [ Time Frame: 15 months ]
    Two minute or Six-Minute Walk Test (depending on patient capability) captures all the walking distance that a patient can demonstrate (in metres)

  9. Feasibility of performing functional assessment at hospital discharge by Short Physical Performance Battery [ Time Frame: 15 months ]
    Short Physical Performance Battery (scoring between 0-10; includes results of the gait speed, balance tests and chair stand)

  10. Feasibility of performing functional assessment at hospital discharge by CPAx score [ Time Frame: 15 months ]
    Chelsea Critical Care Physical Assessment Score (CPAx): scoring 0-5 in 10 domains

  11. Feasibility of collecting metabolic data on ICU: indirect calorimetry [ Time Frame: 15 months ]
    non-invasive metabolic data via indirect calorimetry on ICU

  12. Feasibility of collecting follow-up data by telephone re quality of life: ED5Q survey [ Time Frame: 18 months ]
    Use of ED5Q survey to determine health-related quality of life; scoring 1-5 in 5 domains, plus 1-100 in 1 domain

  13. Feasibility of collecting follow-up data by telephone re job status: Questions on employment status [ Time Frame: 18 months ]
    Questions on employment status (full-time: yes/no; part-time: yes/no)

  14. Feasibility of collecting follow-up data from medical records: number of GP/nurse visits [ Time Frame: 18 months ]
    Information on health care resource usage from number of GP/nurse visits during 12 months post-ICU and hospital discharge

  15. Biochemical analysis of urine [ Time Frame: 18 months ]
    To determine urinary concentrations of beta-hydroxybutyrate and total nitrogen (in mmol/l)

  16. Biochemical analysis of plasma metabolites, beta-hydroxy butyrate, acetoacetate, leucine, and alanine (all measured in the same Arbitrary Units [AU]). [ Time Frame: 18 months ]
    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.



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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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).

Exclusion Criteria:

  • 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

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): NCT04101071


Contacts
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Contact: Angela McNelly, PhD 0203 594 0351 Angela.mcnelly@qmul.ac.uk
Contact: Zudin Puthuchary, PhD 0203 594 0351 z.puthucheary@qmul.ac.uk

Locations
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United Kingdom
Bristol Royal Infirmary Not yet recruiting
Bristol, United Kingdom, BS2 8HW
Contact: Kieron Rooney, MBBS       kieron.rooney@uhbristol.nhs.uk   
Royal London Hospital Recruiting
London, United Kingdom, E1 1BB
Contact: Zudin Puthucheary, PhD       z.puthucheary@qmul.ac.uk   
Contact: Angela McNelly, PhD       angela.mcnelly@qmul.ac.uk   
Sponsors and Collaborators
Barts & The London NHS Trust
Bristol Royal Infirmary
Institute of Child Health
Investigators
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Principal Investigator: Angela McNelly, PhD Royal London Hospital

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Responsible Party: Barts & The London NHS Trust
ClinicalTrials.gov Identifier: NCT04101071     History of Changes
Other Study ID Numbers: 266031
First Posted: September 24, 2019    Key Record Dates
Last Update Posted: October 8, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

(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.

Supporting Materials: Study Protocol
Time Frame: Data will be available once the primary publication is available. It will be available for a period of 10 years.
Access Criteria: Access is available for anyone who is able to provide a reasonable case for their access to the data.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Barts & The London NHS Trust:
Critical care
enteral feeding
nasogastric
ketogenic feed
feasibility
Additional relevant MeSH terms:
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Critical Illness
Disease Attributes
Pathologic Processes