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Trial registered on ANZCTR


Registration number
ACTRN12616001101471
Ethics application status
Approved
Date submitted
21/07/2016
Date registered
15/08/2016
Date last updated
9/08/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Intestinal permeability 'leaky gut' in critically ill patients
Scientific title
Efficacy of using intestinal permeability as a tool to monitor clinical progress in the critically ill
Secondary ID [1] 289350 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Critical illness 298977 0
Increased intestinal permeability 298978 0
Infection/ sepsis 299383 0
Condition category
Condition code
Oral and Gastrointestinal 299366 299366 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Diet and Nutrition 299367 299367 0 0
Other diet and nutrition disorders
Infection 299368 299368 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The degree and location of intestinal permeability will be measured within 72 hours of admission to the Intensive Care Unit and repeated on day 5-6. Baseline urine and blood samples will be collected immediately prior to each test. Intestinal permeability will be measured by administering a sugar solution (1g sucrose, 0.5g rhamnose, 1g mannitol, 1g lactulose, 1g erythritol and 1g sucralose dissolved in 50ml of water) via an enteral feeding tube. A 24 hour urine collection will be conducted following the administration of the sugar solution. The concentration and ratios of select sugars will be analysed in urine samples using gas chromatography- mass spectrometry. Inflammation will be analysed using blood samples. Findings will be compared to results from healthy subjects in a separate study being conducted at La Trobe University (Request ID: 371028).
Intervention code [1] 294928 0
Diagnosis / Prognosis
Comparator / control treatment
Healthy subjects will have intestinal permeability levels measured at one-time point using the method described above in a separate study being conducted at La Trobe University (Request ID: 371028) between July 2014 – December 2017.

Control group
Historical

Outcomes
Primary outcome [1] 298511 0
Composite primary outcome: To assess/investigate the location and degree of intestinal permeability in critically ill adult patients.
Timepoint [1] 298511 0
Intestinal permeability will be measured within 72 hours of Intensive Care Unit admission and repeated on day 5-6 of admission. The degree and location of intestinal permeability will be determined by measuring the concentration and ratios of select sugars in 24 hour urine samples using gas chromatography- mass spectrometry.
Primary outcome [2] 298515 0
To investigate the association between intestinal permeability (measured by urinary sugar analysis) and inflammation.
Timepoint [2] 298515 0
C-reactive protein is being measured as a marker of inflammation using an enzymatic assay. Both serum (for C-reactive protein analysis) and urine samples (for measurement of intestinal permeability) are being obtained within 72 hours of Intensive Care Unit admission and on day 5-6 of admission.
Primary outcome [3] 299252 0
To investigate the association between intestinal permeability (measured by urinary sugar analysis) and corticotropin-releasing factor.
Timepoint [3] 299252 0
Corticotropin-releasing factor is being assessed using an enzyme-linked immunosorbent assay. Serum samples (for corticotropin-releasing factor analysis) and urine samples (for measurement of intestinal permeability) are being obtained within 72 hours of Intensive Care Unit admission and on day 5-6 of admission.
Secondary outcome [1] 326645 0
Primary outcome: To investigate the association between intestinal permeability (measured by urinary sugar analysis) and Intensive Care Unit length of stay (assessed by review of medical records).
Timepoint [1] 326645 0
Intensive Care Unit length of stay is being assessed at discharge from the Intensive Care Unit. Intestinal permeability is being measured within 72 hours of Intensive Care Unit admission and on day 5-6 of admission.
Secondary outcome [2] 326646 0
Primary outcome: To investigate the association between intestinal permeability (measured by urinary sugar analysis) and sepsis.
Timepoint [2] 326646 0
Sepsis is being defined in patients with suspected infection in combination with the Sequential Organ Failure Assessment (SOFA) score as determined from medical records. Sepsis will be assessed within 24 hours of admission, at the same time points as intestinal permeability tests (within 72 hours of admission and on day 5-6 of admission) and on discharge from the Intensive Care Unit.
Secondary outcome [3] 326647 0
Primary outcome: To investigate the association between intestinal permeability (measured by urinary sugar analysis) and multiple organ dysfunction
Timepoint [3] 326647 0
Multiple organ dysfunction is being defined using the Sequential Organ Failure Assessment (SOFA) score as determined from medical records. Multiple organ dysfunction will be assessed within 24 hours of admission, at the same time points as intestinal permeability tests (within 72 hours of admission and on day 5-6 of admission) and on discharge from the Intensive Care Unit.
Secondary outcome [4] 326648 0
To determine the correlation between intestinal permeability (measured by urinary sugar analysis) and nutritional adequacy.
Timepoint [4] 326648 0
Nutritional adequacy will be measured for the first seven days of Intensive Care Unit admission by comparing the amount of nutrition prescribed by the treating team versus the amount of nutrition delivered. Intestinal permeability will be measured within 72 hours of Intensive Care Unit admission and on day 5-6 of admission.

Eligibility
Key inclusion criteria
- Adult patients aged greater than or equal to 18 years;
- Patients receiving or suitable for enteral feeding;
- Likely to be admitted to the ICU for greater than or equal to 3 days;
- Likely to require mechanical ventilation for > 24 hours;
- Patients with an indwelling catheter in situ;
- Patients receiving inotropic or vasopressor support at time of enrolment.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- A past history of gut abnormalities, abdominal surgery within 2 years of ICU admission or malabsorption syndromes;
- Presenting condition or past history of abdominal trauma within 2 years of admission;
- Patients treated with therapeutic hypothermia during admission;
- Patients requiring continuous renal replacement therapy;
- Patients treated with non-steroidal anti-inflammatory drugs;
- Any situation where lactulose or any of the test sugars are used as part of the treatment plan;
- Patients receiving total parenteral nutrition or enteral feeding directly into the small bowel;
- Patients receiving or received chemotherapy or radiotherapy in the past 6 months;
- Pregnancy;
- When participation in the study is not believed to be in the best interest of the patient as determined by the treating physician.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 293922 0
Charities/Societies/Foundations
Name [1] 293922 0
The Australasian Society for Parenteral and Enteral Nutrition
Address [1] 293922 0
P.O.Box 4015
Eight Mile Plains QLD 4113
Country [1] 293922 0
Australia
Primary sponsor type
University
Name
La Trobe University
Address
Discipline of Dietetics and Human Nutrition
Department of Rehabilitation, Nutrition and Sport
School of Allied Health
College of Science, Health and Engineering
La Trobe University
Bundoora
Victoria 3086
Country
Australia
Secondary sponsor category [1] 292745 0
None
Name [1] 292745 0
Address [1] 292745 0
Country [1] 292745 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295338 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 295338 0
PO Royal Melbourne Hospital
Parkville Victoria 3050
Ethics committee country [1] 295338 0
Australia
Date submitted for ethics approval [1] 295338 0
28/10/2015
Approval date [1] 295338 0
14/12/2015
Ethics approval number [1] 295338 0
2015.208
Ethics committee name [2] 295339 0
Alfred Health Human Ethics Committee
Ethics committee address [2] 295339 0
Alfred Health, 55 Commercial Road, Prahran, Melbourne, 3181, Victoria
Ethics committee country [2] 295339 0
Australia
Date submitted for ethics approval [2] 295339 0
24/02/2014
Approval date [2] 295339 0
14/05/2014
Ethics approval number [2] 295339 0
85/14

Summary
Brief summary
Increased intestinal permeability, often referred to as ‘leaky gut’, is a measure of integrity and functioning of the mucosal (innermost) lining of the gastrointestinal tract. Increased levels have been found to correlate with the development of sepsis in the Intensive Care Unit. The location of increased intestinal permeability (gastroduodenal, small bowel and whole gut permeability) has not been adequately explored in the Intensive Care Unit. The aim of the study is to determine the location and degree of changes in intestinal permeability in mechanically ventilated critically ill adult patients. Additionally, this study aims to investigate the association between intestinal permeability, inflammation and clinical outcomes. Findings will be compared to data from healthy subjects being recruited in a separate study at La Trobe University (Request ID: 371028).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 66358 0
A/Prof Audrey Tierney
Address 66358 0
Health Sciences Building 3, Room 438
Discipline of Dietetics and Human Nutrition
Department of Rehabilitation, Nutrition and Sport
School of Allied Health
College of Science, Health and Engineering
La Trobe University
Bundoora
Victoria 3086
Country 66358 0
Australia
Phone 66358 0
+61 (0) 3 9479 5253
Fax 66358 0
Email 66358 0
A.Tierney@latrobe.edu.au
Contact person for public queries
Name 66359 0
A/Prof Audrey Tierney
Address 66359 0
Health Sciences Building 3, Room 438
Discipline of Dietetics and Human Nutrition
Department of Rehabilitation, Nutrition and Sport
School of Allied Health
College of Science, Health and Engineering
La Trobe University
Bundoora
Victoria 3086
Country 66359 0
Australia
Phone 66359 0
+61 (0) 3 9479 5253
Fax 66359 0
Email 66359 0
A.Tierney@latrobe.edu.au
Contact person for scientific queries
Name 66360 0
A/Prof Audrey Tierney
Address 66360 0
Health Sciences Building 3, Room 438
Discipline of Dietetics and Human Nutrition
Department of Rehabilitation, Nutrition and Sport
School of Allied Health
College of Science, Health and Engineering
La Trobe University
Bundoora
Victoria 3086
Country 66360 0
Australia
Phone 66360 0
+61 (0) 3 9479 5253
Fax 66360 0
Email 66360 0
A.Tierney@latrobe.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary