Critical IllnessNCT06115044
The DINE-Normal Proof-of-concept Study
A study testing Intermittent diurnal nutrition and Continuous in people with Critical Illness and Enteral Nutrition, run by North Bristol NHS Trust at 1 site in United Kingdom.
Trial summary
Overarching hypothesis In critically ill adults enteral feeding in a diurnal intermittent pattern improves patient centred outcomes. Research questions for this study Are the same derangements in metabolic and hormonal function observed in healthy volunteers when fed continuously via a nasogastric tube observed in… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Critical Illness, Enteral Nutrition, Time Restricted Feeding
- What is being tested?
- Intermittent diurnal nutrition and Continuous
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 27 Dec 2023to 31 Oct 2024
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults (≥18) on intensive care
- Planned for gastric enteral nutrition (anticipated duration >48 hours)
Who cannot join
- >24 hours after commencement of enteral nutrition
- Gastrointestinal surgery or pathology
- Diabetic emergencies
- Pregnancy
- Parenteral or jejunal nutrition
- Trophic feed only
- Prone positioning
- High risk of refeeding syndrome
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Does Intermittent Nutrition Enterally Normalise Hormonal and Metabolic Responses to Feeding in Critically Ill Adults: The DINE-Normal Proof-of-concept Study
Overarching hypothesis In critically ill adults enteral feeding in a diurnal intermittent pattern improves patient centred outcomes.
Research questions for this study Are the same derangements in metabolic and hormonal function observed in healthy volunteers when fed continuously via a nasogastric tube observed in critically ill patients and can those derangements be mitigated by intermittent diurnal feeding?
Read more
Aim of this study Assess the effect of an enteral nutrition regimen mimicking the usual diurnal meal pattern on hormonal profile and metabolism in critically ill adults. This will generate novel and important proof of concept data and support progression to a clinical trial integrating investigation of physiological responses and patient centred outcomes.
Objectives of this study Laboratory: Characterise patterns of hormone, lipid and metabolite response to intermittent diurnal feeding in critically ill adults.
Clinical: assess feasibility, tolerability (vomiting and gastric residual volume) and efficacy (calorie delivery) of intermittent diurnal feeding in critically ill adults.
Read the detailed description
Setting Single adult general intensive care unit in Bristol with 48 beds and ~2500 admissions annually
Design Parallel group randomised, open-label trial
Population We will recruit from a representative critically ill population and exclude patients with conditions that pose undue risk and/or introduce bias.
See eligibility criteria.
Screening and recruitment Usual care team will screen daily. Eligibility will be confirmed by health care professional on the delegation log and recorded in the ICU clinical information system. This may be done remotely. A screening log will be kept.
Randomisation Via sealed opaque envelopes prepared in advance, allocation 1:1 to intervention or control, stratified by sex.
Consent Enteral nutrition is a necessary intervention. Early nutrition (within hours) is the current standard of care. Prolonged continuous feeding prior to enrolment may bias results. An emergency waiver will be used and deferred consent sought from participants. Where participants lack capacity, this will be from a personal or professional consultee as appropriate.
Intervention Participants will receive their estimated nutritional requirement in 3 equal "meals" each over 30-60 minutes at 0800, 1300, and 1800 with first meal given after an overnight fast from 1900 on the day of enrolment.
Controls Participants will receive their estimated nutritional requirement as continuous feed starting at 0800 after an overnight fast from 1900 on the day of enrolment.
The daily nutritional requirement will be estimated by dietetic staff in the Intensive Care Unit as per usual practice. All other care for both groups will follow usual unit practice as directed by treating intensivist. Once blood sampling for the primary outcome is complete the study intervention period ends and feeding will continue according to usual unit practice.
Blood sampling Primary outcome assessment requires six one-hourly samples will be hourly around the fourth bolus feed with equivalent timing in control group.
Outcomes See outcomes section
Adverse events The natural history of critical illness includes many events that might be considered adverse events or serious adverse events including death, organ failure or nosocomial infection. Such expected events do not need to be reported. Events that are not recorded as study outcomes and are considered possibly related to the study will be reported. The reporting period runs for 72 hours from the start of the overnight fast.
Follow up Routinely collected clinical audit data will be used for ICU and hospital length of stay and mortality.
Sample size Overall sample size is 30. Based on the data from healthy subjects this study is powered to detect smaller (but substantial) effect sizes (d=1.26) with 15 per group while allowing for some drop out.
Analysis Analysis will be undertaken blinded to group allocation. Normality will be tested and appropriate parametric / non-parametric tests used for the primary outcome. Additional analysis of the insulin response (e.g. area under the curve) will be undertaken. Repeated measures ANOVA will be used for physiological secondary outcomes. P < 0.05 will be taken as significant.
- Conditions
- Critical Illness, Enteral Nutrition, Time Restricted Feeding
- Being tested
- Intermittent diurnal nutrition, Continuous
- Medical subject headings
- Critical Illness, Intermittent Fasting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intermittent diurnal nutritionProcedure or surgery
Calculated daily nutritional requirement given as three equal bolus feeds in daytime with prolonged overnight fast
ContinuousProcedure or surgery
Calculated daily nutritional requirement given over 24 hours
| Study group | Role | What they receive |
|---|---|---|
| Intermittent | Experimental | Bolus feeding over 30 to 60 minutes at 0800, 1300 and 1800 Receives: Procedure: Intermittent diurnal nutrition |
| Continuous | Active comparator | Continuous feeding over 24 hours Receives: Procedure: Continuous |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin
Plasma insulin and C-Peptide
Measured: Peak within 3 hours of bolus feed (comparable time point in comparator)
Secondary outcomes (12)
Urea
mmol/L
Measured: Study day 1 and study day 2
Glucagon-like peptide 1
pmol/L
Measured: Study day 1 and study day 2
Ketones
beta-hydroxybutyrate, mmol/L
Measured: Study day 1 and study day 2
Non-esterified fatty acids
mmol/L
Measured: Study day 1 and study day 2
Triglyceride
mmol/L
Measured: Study day 1 and study day 2
Glycerol
umol/L
Measured: Study day 1 and study day 2
Calories delivered
Calories delivered (absolute and % of target)
Measured: Study day 1 and study day 2
Incidence of gastrointestinal upset (GI upset)
Number of events of delayed gastric emptying, vomiting, diarrhoea, ileus, constipation, aspiration of feed
Measured: Study day 1 and study day 2
Mortality
All cause crude mortality
Measured: ICU and acute hospital
Length of stay
Length of stay (days)
Measured: ICU and acute hospital
Delta-SOFA
Difference between baseline and end of intervention sequential organ failure assessment
Measured: Day 0 and day 2
Compliance
Protocol violations
Measured: Study day 1 and study day 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2023
- Study start27 Dec 2023
- Primary completion24 Apr 2024
- Study completion31 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)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
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- North Bristol NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- University of Bath, University of Bristol, University of the West of England
- Responsible party
- Principal investigator, Matt Thomas, North Bristol NHS Trust
- Investigators
- Matt Thomas, Principal investigator, North Bristol NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06115044
- Sponsor's protocol ID
- R&D 5454
- Other IDs
- IRAS 328469
- Status last verified
- May 2025
- First submitted
- 24 Oct 2023
- Last updated
- 25 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Applications for access to the final trial dataset will be considered by the Chief Investigator and Sponsor after publication of trial results.
Publications
Beattie CE, Borislava B, Smith HA, Ambler MT, White P, Milne D, Ramesh AV, Ferriman A, Fisher T, Horsley C, Jackson S, Jubainville C, Lobo K, Maxfield H, Gonzalez JT, Betts JA, Pickering AE, Thomas M. Does Intermittent Nutrition Enterally Normalise hormonal and metabolic responses to feeding in critically ill adults? The DINE-normal proof-of-concept study. Clin Nutr. 2025 Dec;55:81-89. doi: 10.1016/j.clnu.2025.10.003. Epub 2025 Oct 30.
PubMed 41197596Beattie CE, Thomas M, Borislavova B, Smith HA, Ambler M, White P, Hayes K, Milne D, Ramesh AV, Gonzalez JT, Betts JA, Pickering AE. Does intermittent nutrition enterally normalise hormonal and metabolic responses to feeding in critically ill adults? A protocol for the DINE-Normal proof-of-concept randomised parallel-group study. BMJ Open. 2024 Nov 24;14(11):e086540. doi: 10.1136/bmjopen-2024-086540.
PubMed 39581721
Study at a glance
From the registry record, last updated by the sponsor on 25 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Does Intermittent Nutrition Enterally Normalise Hormonal and Metabolic Responses to Feeding in Critically Ill Adults: The DINE-Normal Proof-of-concept Study
- ClinicalTrials.gov ID
- NCT06115044
- Acronym / sponsor ID
- R&D 5454
- Conditions
- Critical Illness, Enteral Nutrition, Time Restricted Feeding
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- North Bristol NHS TrustUniversity, hospital or other
- Collaborators
- University of Bath, University of Bristol, University of the West of England
- Study start
- 27 Dec 2023 (actual)
- Primary completion
- 24 Apr 2024 (actual)
- Study completion
- 31 Oct 2024 (actual)
- First posted
- 2 Nov 2023 (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.
Overarching hypothesis In critically ill adults enteral feeding in a diurnal intermittent pattern improves patient centred outcomes.
Research questions for this study Are the same derangements in metabolic and hormonal function observed in healthy volunteers when fed continuously via a nasogastric tube observed in critically ill patients and can those derangements be mitigated by intermittent diurnal feeding?
Aim of this study Assess the effect of an enteral nutrition regimen mimicking the usual diurnal meal pattern on hormonal profile and metabolism in critically ill adults. This will generate novel and important proof of concept data and support progression to a clinical trial integrating investigation of physiological responses and patient centred outcomes.
Objectives of this study Laboratory: Characterise patterns of hormone, lipid and metabolite response to intermittent diurnal feeding in critically ill adults.
Clinical: assess feasibility, tolerability (vomiting and gastric residual volume) and efficacy (calorie delivery) of intermittent diurnal feeding in critically ill adults.
Detailed description
Setting Single adult general intensive care unit in Bristol with 48 beds and ~2500 admissions annually
Design Parallel group randomised, open-label trial
Population We will recruit from a representative critically ill population and exclude patients with conditions that pose undue risk and/or introduce bias.
See eligibility criteria.
Screening and recruitment Usual care team will screen daily. Eligibility will be confirmed by health care professional on the delegation log and recorded in the ICU clinical information system. This may be done remotely. A screening log will be kept.
Randomisation Via sealed opaque envelopes prepared in advance, allocation 1:1 to intervention or control, stratified by sex.
Consent Enteral nutrition is a necessary intervention. Early nutrition (within hours) is the current standard of care. Prolonged continuous feeding prior to enrolment may bias results. An emergency waiver will be used and deferred consent sought from participants. Where participants lack capacity, this will be from a personal or professional consultee as appropriate.
Intervention Participants will receive their estimated nutritional requirement in 3 equal "meals" each over 30-60 minutes at 0800, 1300, and 1800 with first meal given after an overnight fast from 1900 on the day of enrolment.
Controls Participants will receive their estimated nutritional requirement as continuous feed starting at 0800 after an overnight fast from 1900 on the day of enrolment.
The daily nutritional requirement will be estimated by dietetic staff in the Intensive Care Unit as per usual practice. All other care for both groups will follow usual unit practice as directed by treating intensivist. Once blood sampling for the primary outcome is complete the study intervention period ends and feeding will continue according to usual unit practice.
Blood sampling Primary outcome assessment requires six one-hourly samples will be hourly around the fourth bolus feed with equivalent timing in control group.
Outcomes See outcomes section
Adverse events The natural history of critical illness includes many events that might be considered adverse events or serious adverse events including death, organ failure or nosocomial infection. Such expected events do not need to be reported. Events that are not recorded as study outcomes and are considered possibly related to the study will be reported. The reporting period runs for 72 hours from the start of the overnight fast.
Follow up Routinely collected clinical audit data will be used for ICU and hospital length of stay and mortality.
Sample size Overall sample size is 30. Based on the data from healthy subjects this study is powered to detect smaller (but substantial) effect sizes (d=1.26) with 15 per group while allowing for some drop out.
Analysis Analysis will be undertaken blinded to group allocation. Normality will be tested and appropriate parametric / non-parametric tests used for the primary outcome. Additional analysis of the insulin response (e.g. area under the curve) will be undertaken. Repeated measures ANOVA will be used for physiological secondary outcomes. P < 0.05 will be taken as significant.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intermittent | Experimental | Procedure: Intermittent diurnal nutritionBolus feeding over 30 to 60 minutes at 0800, 1300 and 1800 |
| Continuous | Active comparator | Procedure: ContinuousContinuous feeding over 24 hours |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Adults (≥18) on intensive care
- Planned for gastric enteral nutrition (anticipated duration >48 hours)
Key exclusion criteria (8 listed)
- >24 hours after commencement of enteral nutrition
- Gastrointestinal surgery or pathology
- Diabetic emergencies
- Pregnancy
- Parenteral or jejunal nutrition
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 |
|---|---|---|
| Intermittent diurnal nutritionCalculated daily nutritional requirement given as three equal bolus feeds in daytime with prolonged overnight fast | Procedure or surgery | Intermittent |
| ContinuousCalculated daily nutritional requirement given over 24 hours | Procedure or surgery | Continuous |
Primary outcome
Insulin
Time frame: Peak within 3 hours of bolus feed (comparable time point in comparator)
Plasma insulin and C-Peptide
12 secondary outcomes
Urea
Time frame: Study day 1 and study day 2
Glucagon-like peptide 1
Time frame: Study day 1 and study day 2
Ketones
Time frame: Study day 1 and study day 2
Non-esterified fatty acids
Time frame: Study day 1 and study day 2
Triglyceride
Time frame: Study day 1 and study day 2
Glycerol
Time frame: Study day 1 and study day 2
Calories delivered
Time frame: Study day 1 and study day 2
Incidence of gastrointestinal upset (GI upset)
Time frame: Study day 1 and study day 2
Mortality
Time frame: ICU and acute hospital
Length of stay
Time frame: ICU and acute hospital
Delta-SOFA
Time frame: Day 0 and day 2
Compliance
Time frame: Study day 1 and study day 2
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 25 May 2025.
- Derived from this study: PubMed 41197596Beattie CE, Borislava B, Smith HA, Ambler MT, White P, Milne D, Ramesh AV, Ferriman A, Fisher T, Horsley C, Jackson S, Jubainville C, Lobo K, Maxfield H, Gonzalez JT, Betts JA, Pickering AE, Thomas M. Does Intermittent Nutrition Enterally Normalise hormonal and metabolic responses to feeding in critically ill adults? The DINE-normal proof-of-concept study. Clin Nutr. 2025 Dec;55:81-89. doi: 10.1016/j.clnu.2025.10.003. Epub 2025 Oct 30.
- Derived from this study: PubMed 39581721Beattie CE, Thomas M, Borislavova B, Smith HA, Ambler M, White P, Hayes K, Milne D, Ramesh AV, Gonzalez JT, Betts JA, Pickering AE. Does intermittent nutrition enterally normalise hormonal and metabolic responses to feeding in critically ill adults? A protocol for the DINE-Normal proof-of-concept randomised parallel-group study. BMJ Open. 2024 Nov 24;14(11):e086540. doi: 10.1136/bmjopen-2024-086540.
- Individual participant dataSharing planned: Yes. Applications for access to the final trial dataset will be considered by the Chief Investigator and Sponsor after publication of trial results.
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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.
Matt Thomas principal investigator
North Bristol NHS Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intermittent diurnal nutrition and Continuous in people with Critical Illness and Enteral Nutrition, run by North Bristol NHS Trust at 1 site 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 2 inclusion and 8 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 25 May 2025. 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 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?
Insulin (time frame: Peak within 3 hours of bolus feed (comparable time point in comparator)). 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 NCT06115044, which also lists 2 linked publications.
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 25 May 2025.