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Trial registered on ANZCTR


Registration number
ACTRN12621000832875
Ethics application status
Approved
Date submitted
11/05/2021
Date registered
30/06/2021
Date last updated
30/06/2021
Date data sharing statement initially provided
30/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Prebiotics, the gastrointestinal microbiome and clinical outcomes post allogeneic stem cell transplantation
Scientific title
Tolerance of prebiotic containing enteral nutrition post allogeneic stem cell transplantation.
Secondary ID [1] 304205 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
stem cell transplantation 321895 0
graft versus host disease 322223 0
enteral nutrition 322224 0
Condition category
Condition code
Diet and Nutrition 319624 319624 0 0
Other diet and nutrition disorders
Blood 319917 319917 0 0
Haematological diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study aims to compare enteral feed tolerance, microbial diversity, microbiome composition and clinical outcomes between patients who receive standard non fibre enteral nutrition (EN) vs prebiotic containing EN post allogeneic stem cell transplantation. Patients will be allocated to standard or prebiotic EN consecutively (first 10 patients recruited will be allocated to standard care, last 20 patients to intervention). Nutrition support is provided while participants are inpatients for stem cell transplantation. Conditioning pre transplant will be as per usual care, for 5-12 days depending on regimen.

Participants in both groups will commence EN, increase the feeding rate and cease feeding as per usual care. This includes commencing EN on day +1 post transplant at 30ml/hr of continuous feeding via a 10-12fr nasogastric tube, increasing to 50ml/hr when oral intake declines to <50% of meals and increasing to goal EN (providing 100% of estimated requirements) if oral intake is minimal. If EN ceases due to intolerance and oral intake is poor, patients will be converted to parenteral nutrition (PN). Both EN and PN will cease once oral intake is >50% meals and 2 high protein drinks/ day post neutrophil engraftment. During provision of nutrition support patients will be provided with high protein high energy meals and snacks and encouraged to continue oral intake if tolerated.

Participants allocated to receive the prebiotic EN will receive a polymeric ready to hang formula (1.2kcal/ml, 63g protein,15g fibre /L) containing inulin, oligofructose, arabic gum, soy polysaccharides, cellulose and resistant starch, instead of the usual non fibre EN formula. Tolerance of EN will be monitored and if poor, participants will be changed to PN as per standard care. Adherance to the intervention is monitored by review of the participants fluid balance charts and documenting the amount of prescribed feed actually received.

Stool samples will be collected pre conditioning, post conditioning and at day 12-18 post transplant (peri engraftment). Blood samples will be collected post conditioning and at two weeks post transplant. Clinical outcomes will be collected during the transplant admission and at day 100. Oral intake will be monitored for three days pre conditioning (participants will complete a paper food diary or record intake in the 'Easy diet diary' app) and for two weeks post transplant while inpatients (paper diary).
Intervention code [1] 320537 0
Treatment: Other
Comparator / control treatment
Participants on the standard care arm of the study will commence EN as per usual care, as per the transplant units ‘Allogeneic stem cell transplant nutrition support protocol’. This involves provision of a polymeric non-fibre ready to hang formula (1.2 kcal/ml, 63 g protein/L) from day +1 post transplant, while participants are inpatients. Enteral nutrition is commenced at 30ml/hr of continuous feeding via a 10-12fr nasogastric tube, increasing to 50ml/hr when oral intake declines and increasing to goal EN (providing 100% of estimated requirements) if oral intake is minimal. If EN ceases due to intolerance and oral intake is poor and a further week of poor oral intake is anticipated, patients will be converted to parenteral nutrition (PN). Both EN and PN will cease once oral intake is >50% meals and 2 high protein drinks/ day post neutrophil engraftment. Stool samples will be collected pre conditioning, post conditioning and at day 12-18 post transplant (peri engraftment). Blood samples will be collected post conditioning and at two weeks post transplant. Clinical outcomes will be collected during the transplant admission and at day 100. Oral intake will be monitored for three days pre conditioning (paper diary or Easy diet diary app) and for two weeks post transplant (paper diary). .
Control group
Active

Outcomes
Primary outcome [1] 327481 0
Tolerance of a prebiotic EN formulation, defined as the proportion of patients who do not require cessation of the EN and commencement of PN as per the ‘Allogeneic stem cell transplant nutrition support protocol’. This will be assessed through accessing the participants medical record.
Timepoint [1] 327481 0
Assessed at time of hospital discharge after cessation of all supplementary nutrition support.
Secondary outcome [1] 395288 0
Amount of prescribed enteral nutrition received. This will be assessed through review of the participants daily fluid balance charts.
Timepoint [1] 395288 0
Collected daily during provision of enteral nutrition until hospital discharge/ cessation feeding.
Secondary outcome [2] 395289 0
Duration of enteral nutrition. This will be assessed through review of the participants medical records.
Timepoint [2] 395289 0
Assessed at hospital discharge
Secondary outcome [3] 395290 0
Nutritional status: Subjective Global Assessment (SGA)
Timepoint [3] 395290 0
Assessed pre transplant and pre discharge while participants are inpatients
Secondary outcome [4] 395291 0
Length of hospital stay. This will be assessed through review of the participants medical record.
Timepoint [4] 395291 0
Assessed at hospital discharge
Secondary outcome [5] 395292 0
Incidence of infections: Common Terminology Criteria for Adverse Events (CTCAE) >grade 2
Timepoint [5] 395292 0
Pre conditioning then daily while inpatients until two weeks post transplant
Secondary outcome [6] 395293 0
Incidence of acute graft versus host disease (GVHD). This will be assessed through accessing the participants medical record and recording when GVHD has been diagnosed by a Haematologist.
Timepoint [6] 395293 0
100 days post transplant
Secondary outcome [7] 395294 0
Mortality (assessed through reviewing the participants medical record)
Timepoint [7] 395294 0
100 days post transplant
Secondary outcome [8] 395295 0
Abundance of short chain fatty acid producing bacteria in the gastrointestinal microbiome (assessed through shotgun metagenomic sequencing of stool sample)
Timepoint [8] 395295 0
Pre conditioning and two weeks post transplant. A third stool sample collected post conditioning (between day-1 pre transplant to day +1 post transplant) will be stored for future analysis.
Secondary outcome [9] 395296 0
Short chain fatty acid levels in stool (assessed through liquid chromatography mass spectrometry)
Timepoint [9] 395296 0
Post conditioning (between day-1 pre transplant to day +1 post transplant) and two weeks post transplant
Secondary outcome [10] 396605 0
Microbial diversity (assessed through shotgun metagenomic sequencing and shannon diversity index)
Timepoint [10] 396605 0
Assessed at 3 timepoints: baseline pre conditioning, post conditioning (between day-1 pre transplant to day +1 post transplant) and two weeks post transplant.
Secondary outcome [11] 396606 0
Short chain fatty acid levels in blood (assessed through liquid chromatography mass spectrometry)
Timepoint [11] 396606 0
Post conditioning (between day-1 pre transplant to day +1 post transplant) and two weeks post transplant
Secondary outcome [12] 396607 0
Oral fibre intake (assessed through participants completion of a food diary and analysis through Foodworks)
Timepoint [12] 396607 0
Baseline pre conditioning then daily while inpatients from day -2 pre transplant to two weeks post transplant
Secondary outcome [13] 396608 0
Oral energy intake (assessed through participants completion of a food diary and analysis through Foodworks)
Timepoint [13] 396608 0
Baseline pre conditioning then daily while inpatients from day -2 pre transplant to two weeks post transplant
Secondary outcome [14] 396609 0
Oral protein intake (assessed through participants completion of a food diary and analysis through Foodworks)
Timepoint [14] 396609 0
Baseline pre conditioning then daily while inpatients from day -2 pre transplant to two weeks post transplant
Secondary outcome [15] 396610 0
Duration of mucositis (grade assessed through World Health Organisation criteria and monitored via review of the participants medical charts)
Timepoint [15] 396610 0
Assessed at hospital discharge (number of days of mucositis from transplant to discharge)
Secondary outcome [16] 396611 0
Duration of diarrhoea (assessed using CTCAE criteria)
Timepoint [16] 396611 0
Assessed at hospital discharge (number of days of diarrhoea from transplant to discharge)
Secondary outcome [17] 396612 0
Disease relapse (assessed through documentation in medical chart by Haematologist)
Timepoint [17] 396612 0
100 days post transplant
Secondary outcome [18] 396613 0
Duration of neutropenia from transplant (neutrophils <0.5x109/L as per blood test results)
Timepoint [18] 396613 0
At hospital discharge

Eligibility
Key inclusion criteria
Patients aged 18 or older undergoing allogeneic myeloablative or reduced intensity myeloablative allogeneic stem cell transplantation at the Royal Brisbane and Womens Hospital who can provide written informed consent.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients already enrolled on a GVHD prevention study, hepatitis B, hepatitis C or HIV infection or intolerance or allergy to any ingredient in the enteral feed.

Study design
Purpose of the study
Treatment
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
Not Applicable
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
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)
QLD

Funding & Sponsors
Funding source category [1] 308578 0
Charities/Societies/Foundations
Name [1] 308578 0
Nutricia Research Foundation
Address [1] 308578 0
Nutricia Research Foundation
Conradpark 3
2441AE Nieuwveen
The Netherlands
Country [1] 308578 0
Netherlands
Primary sponsor type
Hospital
Name
Royal Brisbane and Womens Hospital
Address
Butterfield St
Herston
Queensland 4029
Australia
Country
Australia
Secondary sponsor category [1] 309436 0
None
Name [1] 309436 0
n/a
Address [1] 309436 0
n/a
Country [1] 309436 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308519 0
Royal Brisbane and Womens Hospital
Ethics committee address [1] 308519 0
Butterfield St
Herston
Queensland 4029
Australia
Ethics committee country [1] 308519 0
Australia
Date submitted for ethics approval [1] 308519 0
Approval date [1] 308519 0
11/05/2021
Ethics approval number [1] 308519 0

Summary
Brief summary
Patients undergoing allogeneic stem cell transplantation frequently require enteral (nasogastric) feeding however the best formula to provide is unclear.
Some research has found that the type and diversity of gastrointestinal bacteria (microbiome) may be linked to differences in health outcomes after
transplant. Prebiotic fibre may assist in increasing the diversity of the microbiome and the abundance of beneficial bacteria. The aim of this pilot study is to investigate the use of a prebiotic fibre containing enteral feed and its effect on the microbiome and health outcomes after transplantation. This study will recruit 10 participants who are receiving the standard fibre free enteral feed and 20 participants to receive a prebiotic containing feed. Data on clinical outcomes will be collected as well as stool and blood samples before transplant and 2 weeks post, to assess changes in the microbiome. This research will help in improving care for future patients by increasing knowledge on the best enteral
feed formula to provide after stem cell transplantation.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 110990 0
Ms Sarah Andersen
Address 110990 0
Department of Nutrition and Dietetics
Royal Brisbane and Womens Hospital
Butterfield St
Herston
Queensland 4029
Country 110990 0
Australia
Phone 110990 0
+61 7 36468268
Fax 110990 0
Email 110990 0
sarah.andersen@health.qld.gov.au
Contact person for public queries
Name 110991 0
Ms Sarah Andersen
Address 110991 0
Department of Nutrition and Dietetics
Royal Brisbane and Womens Hospital
Butterfield St
Herston
Queensland 4029
Country 110991 0
Australia
Phone 110991 0
+61 7 36468268
Fax 110991 0
Email 110991 0
sarah.andersen@health.qld.gov.au
Contact person for scientific queries
Name 110992 0
Ms Sarah Andersen
Address 110992 0
Department of Nutrition and Dietetics
Royal Brisbane and Womens Hospital
Butterfield St
Herston
Queensland 4029
Country 110992 0
Australia
Phone 110992 0
+61 7 36468268
Fax 110992 0
Email 110992 0
sarah.andersen@health.qld.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
No Results