Improved Quality of Life in Children With Intestinal Failure - a Randomised Intervention Trial
Phase: NA
Conditions: Intestinal Pseudo-Obstruction, Short Bowel Syndrome, Malabsorption Syndrome Autoimmune Enteropathy, Bacterial Overgrowth
Sponsor: Oslo University Hospital

21/06/2021 
 
Study protocol: Improved quality of life in children with intestinal failure 
 
 
 
 
 
Improved quality of life in children with intestinal failure  
– a randomised controlled intervention trial 
 
 

21/06/2021 
 
Study protocol: Improved quality of life in children with intestinal failure 
Improved quality of life in children with intestinal failure. 
Research questions and hypotheses, theoretical approach and methodology 
We hypothesize that prebiotics will improve QoL in children with intestinal failure (IF) by reducing 
bacterial overgrowth and hence restore the microbiota towards a healthier gut.  
Primary aim: 
 
Determine whether prebiotics improves QoL (primary endpoint) in IF children. 
 
Secondary aims:  
 
Study changes in microbiota and production of short chain fatty acids (secondary endpoints). 
 
Explore effects of prebiotics on GI-symptoms, changes in tolerance for enteral nutrition and 
need for antibiotic treatment.  
Overview 
The project consists of two work packages (WPs): Effect of prebiotics on microbiota (WP1) and Effect 
of prebiotics on quality of life (WP2), as illustrated in figure 3. The main study (WP2) is a randomised 
controlled trial.  
Setting: Paediatric patients with IF are routinely followed at Oslo University Hospital (OUH) by a 
multidisciplinary team with expertise in the treatment of IF. Patients will be identified through this 
team and recruited by research workers (PhD student/research assistant). 
Patients:  Patients aged 1 to 18 years that fit one of the inclusion criteria will be invited to participate 
in the study by letter. 
 Inclusion criteria are:  
 
Diagnosed with congenital malformations or diseases requiring intestinal surgery leading to 
short bowel syndrome. 
or 
 
Diagnosed with conditions and diseases leading to IF. 
and 
 
Treated with parenteral nutrition for a periode of  >3months 
Exclusion criteria:  
 
Children in need of temporary advanced nutrition intervention due to illness, e.g. infections. 
 
Children with temporary malfunctioning gut due to advanced medical treatment, for 
example cancer treatment or transplantation 
WP1. Effect of Prebiotics on microbiota (proof of concept). 
The short-time effects of prebiotics on microbiota will be evaluated in an open 4-week intervention, 
to establish a proof of concept. 
 
Task 1.1 Recruitment of participants 
The patients will be recruited in connection with routine follow-ups at OUH. 
 
Task 1.2 Run-in period 
To ensure that the participants have a stable microbiota prior to the intervention we will use 
a run-in period before the intervention. Data collected at the start of the run-in are: QoL, 
Stool sample, stool consistency and use of antibiotics. Any hospital admissions or need for 
antibiotics during the run-in period will be recorded.  

21/06/2021 
 
Study protocol: Improved quality of life in children with intestinal failure 
 
Task 1.3 Intervention 
Data collected before and after the intervention include: QoL, stool sample, blood samples, 
nutritional intake (diet, enteral and intravenous nutrition), stool consistency and use of 
antibiotics . Participants are provided with sachets of prebiotics to ingest daily for 4 weeks of 
Phase 1 intervention. The dosage will be prescribed according to weight. The patients are 
then invited to the hospital for a follow-up of phase 1.  
WP2 Effect of Prebiotics on Quality of Health 
T2.1 Randomisation of participants from Phase 1 
Participants will be randomised into two groups after completing Phase 1. One group will 
continue to use prebiotics (Stimulance), while the other group will not receive any 
intervention. Microbiota is known to return to its habitual flora within few weeks after short-
term intervention. The group without prebiotic treatment will therefore act as a control 
group.  
T2.2 Intervention Phase 2 
The participants in the intervention group continues with prebiotics (Stimulance) for another 
6 months. The dosage will be adjusted if necessary, pending the observations in Phase 1. 
Data collected at the end of the intervention include: QoL, stool sample, blood samples, 
nutritional intake (diet, enteral and intravenous nutrition), stool consistency and use of 
antibiotics. We will compare the intervention group with the control group. In addition, the 
intervention group will serve as their own control before and after the intervention with 
prebiotics. The study design is useful to account for the inter-individual make-up of the 
microbiota that contributes to a large portion of variability between subjects.  
 
Endpoint:  
Primary endpoint will be QoL score compared between the two groups at 6-months follow-up. QoL 
will be scored using two published and validated questionnaires: PedsQL 4.0 and PedsQL 3.0 
Gastrointestinal Symptoms Scales (PedsQL GI). Scoring will be done at run-in, before and after phase 
1 and at the end of phase 2. This enables us to study changes between the two groups (primary 
endpoint) and changes within the subjects before and after intervention with prebiotics. 
Secondary endpoint will include changes in the microbiota measured indirectly by the production of 
SFCAs, the microbiota composition and diversity. In addition, relevant clinical outcomes will be 
obtained and analysed. 
 
Methods: 
 
 
Stool samples will be collected using a provided stool collection kit with written instructions for 
the participant/parents. The sample will be collected in a tube and stored at home in the freezer 
in a specialised container until pick-up or hospital visit. The samples will be analysed for SCFA and 
total organic acid content using HPLC, while microbiota will be analysed in faecal samples using 
established techniques (16S rRNA amplicon sequencing and reduced metagenome sequencing). 
Faecal inflammation biomarkers will also be analysed. The main effect of the intervention on the 
microbiota will be tested based on crude alpha and beta diversity indices but we will also apply 
advanced multivariate methods. 

21/06/2021 
 
Study protocol: Improved quality of life in children with intestinal failure 
 
Diet will be recorded before and after phase 1 and at the end of phase 2:  
 
Repeated 24 hr recall (2 days). Nutritional analysis will be done by use of the software 
DietistPro, which is implemented and used by dieticians at OUH, as well as in the other 
Nordic countries (www.kostdata.se/nb/dietistnet/dietist-net-pro). 
 
Questionnaire to collect data on the use of nutritional supplements, vitamin- and mineral 
supplements, food avoidance, food allergies, food intolerances, enteral and intravenous 
nutrition. 
 
Clinical data (blood samples, GI-function, anthropometric data and other medical information) 
will be collected at run-in, before and after phase 1 and at the end of phase 2. 
Outcomes and measurements 
Outcome 
Measurements 
PRIMARY 
 
Quality of life 
QoL questionnaires: 
PedsQL and PedsQL Gastrointestinal symptoms scale 
SECONDARY 
 
Faeces 
SCFA (HPLC), Organic Acids (HPLC), Microbiota composition (16S 
rRNA amplicon sequencing and reduced metagenome sequencing), 
inflammation markers (calprotectin)  
Blood samples: 
 
Biomarkers of intestinal leakage (albumin, Lipopolysaccharide-
binding protein, citrulline)  
Biomarkers of intestinal absorption (iron status, vitamin status) 
Infection and inflammatory parameters (CRP, ESR, full blood count) 
Nutritional record 
Nutrient intake from food, drink, feeding tube (enteral nutrition), 
intravenous nutrition and supplements 
Clinical status: 
 
Anthropometrics: Weight, height, BMI 
GI-Function: stool frequency and consistency (Bristol Stool Scale) 
Electronic patient record: Diagnosis, medical complications, 
antibiotic treatment 
 
Ethical considerations: 
The intervention is a limited time supplementation with prebiotics. The product (Stimulance©) is 
approved for enteral use and is not expected to do any harm to the participants. However, any 
adverse events will be recorded. The project is approved by the Regional Ethical Committee (REK), nr 
170851. The project will be registered at Helsenorge.no and Clinicaltrials.gov.