Alternative Substrates in the Critically Ill Subject

NCT04101071 | Completed DMC

• 1 other identifier: 266031
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 2

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).

Conditions

Critical Illness

Keywords

Critical care; enteral feeding; nasogastric; ketogenic feed; feasibility

Outcome Measures

Primary Outcomes (15)

• Feasibility of patient recruitment; number eligible from screening

  Number of patients screened

  15 months

• Feasibility of patient recruitment; percentage eligible from screening

  Percentage of patients eligible for recruitment

  15 months

• Feasibility of patient recruitment; number from consent process

  Number of eligible patients able to be consented to join the study

  15 months

• Feasibility of patient recruitment: percentage from consent process

  Percentage of eligible patients able to be consented to join the study

  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

  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

  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.

  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.

  15 months

• Coefficient of Glucose Variation (scored as mean/standard deviation)

  Coefficient of Glucose Variation (scored as mean/standard deviation)

  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

  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

  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

  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)

  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

  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

  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

  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

  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

  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

  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

  15 months

Study Arms (2)

Modular ketogenic enteral feed

EXPERIMENTAL

Ketogenic enteral feed to be administered continuously for 10 days.

Other: Modular ketogenic feed

Standard enteral feed

ACTIVE COMPARATOR

Standard enteral feed to be administered continuously for 10 days.

Other: Standard feed

Interventions

Modular ketogenic feed OTHER

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

Modular ketogenic enteral feed

Standard feed OTHER

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

Standard enteral feed

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Barts & The London NHS Trust: lead
• Bristol Royal Infirmary: collaborator
• Institute of Child Health: collaborator

Study Sites (2)

Bristol Royal Infirmary

Bristol, BS2 8HW, United Kingdom

Location

Royal London Hospital

London, E1 1BB, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 38102152 DERIVED

MeSH Terms

Conditions

Critical Illness

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Angela McNelly, PhD

  Royal London Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: SIngle blinded, randomised, controlled feasibility study

Study Record Dates

• First Submitted: June 26, 2019
• First Posted: September 24, 2019
• Study Start: October 2, 2019
• Primary Completion: April 27, 2022
• Study Completion: April 27, 2022
• Last Updated: August 1, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: 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.

Locations

GB (2)