iPENS: The Intensive Post Exclusive Enteral Nutrition Study

Sponsor

NHS Greater Glasgow and Clyde (Other)

Overall Status

Recruiting

CT.gov ID

NCT04225689

Collaborator

University of Glasgow (Other)

Enrollment

Locations

Arms

48.7

Anticipated Duration (Months)

11.6

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Crohn's disease (CD) is a chronic inflammatory condition with phases where the disease is active and other, where there are no symptoms. Exclusive enteral nutrition (EEN), a liquid only diet without allowance of any extra food, is the main treatment for children with active CD. However, when children stop the liquid diet and return to their normal diet, most of them will experience an increase in their gut inflammation, mostly without symptoms initially. The aim of this study is to investigate this phenomenon by exploring if diet and gut bacteria play a role. Furthermore, the investigators aim to test whether a new, ordinary food-based diet, called the Crohn's Disease TReatment with EATing (CD-TREAT) diet can help control gut inflammation during the early food reintroduction phase, after EEN completion, compared to an unrestricted, free diet.

Condition or Disease	Intervention/Treatment	Phase
Crohn Disease	Other: CD-TREAT diet	N/A

Detailed Description

A maximum of 60 participants, who have successfully responded to EEN, will be allocated to the study arms with block randomisation, with a 1:1 allocation, in random size blocks. The electronic randomisation process will be performed by an independent researcher. Those participants who do not wish to be randomised to one of the two study arms, will be offered the chance to be allocated to the group of their preference. Using this approach, inclusion of all eligible participants will be ensured, as excluding those who do not wish to be randomised, may reduce the generalisation of findings and minimise statistical power of a study with modest eligible population to recruit from.

CD-TREAT diet (intervention group)

Participants in the intervention group will consume the CD-TREAT diet exclusively without being allowed to consume additional food, for the first 3 weeks of food reintroduction, after EEN completion. They will be provided with a tailored, dietitian-devised diet, which has been designed to replicate the nutritional composition of EEN. The intervention will be overseen by qualified dietitians, including a National Health Service (NHS) research dietitian.

Unrestricted diet (control group)

Participants in the control group will consume a free, unrestricted diet for the same period, as the intervention group.

Participants in both groups will record their diet on a daily basis. The investigators will meet the participants weekly to address any potential issues they may have during the trial and to review the dietary assessment process. Standard treatment for maintenance of clinical remission will be continued, as designated by the medical team.

Participants will be asked to provide serial faecal and urine samples (n=8). Collection of a maximum of 2 blood samples, anthropometric measurements and assessment of disease activity and quality of life will be performed before and after the end of the dietary intervention. Participants will also be followed through their clinical records until they clinically relapse, or maximum up to a year after EEN completion.

The primary endpoint is the comparison of faecal calprotectin levels between the two groups at the end of the dietary intervention (3 weeks after EEN completion).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

58 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Masking Description:

Electronic random block-size randomisation will be performed by a researcher not involved in study recruitment. Allocation to study arm will be revealed to participants after provision of informed consent.

Primary Purpose:

Other

Official Title:

The Intensive Post Exclusive Enteral Nutrition Study (iPENS): A Randomised Trial to Evaluate CD-TREAT Diet as a Food Reintroduction Regime in Children and Young Adults With Crohn's Disease

Actual Study Start Date :

Jan 10, 2020

Anticipated Primary Completion Date :

Jan 1, 2023

Anticipated Study Completion Date :

Feb 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CD-TREAT diet Solid food-based dietary intervention replicating composition of exclusive enteral nutrition (EEN). Daily for a maximum of 21 days. Individualised diet based on energy requirements and physical activity levels.	Other: CD-TREAT diet Dietary intervention
No Intervention: Unrestricted diet Free, unrestricted diet. Daily for a maximum of 21 days.

Arm

Intervention/Treatment

Experimental: CD-TREAT diet

Solid food-based dietary intervention replicating composition of exclusive enteral nutrition (EEN). Daily for a maximum of 21 days. Individualised diet based on energy requirements and physical activity levels.

Other: CD-TREAT diet

Dietary intervention

No Intervention: Unrestricted diet

Free, unrestricted diet. Daily for a maximum of 21 days.

Outcome Measures

Primary Outcome Measures

Colonic inflammation [Baseline to 21 days post EEN completion]
Comparison of faecal calprotectin levels between the intervention (CD-TREAT) and the control (unrestricted diet) group

Secondary Outcome Measures

Diet and faecal microbiome [Baseline to 21 days post EEN completion]
Association of fermentable carbohydrates intake with relative abundance of faecal bacteria
Diet and faecal metabolome [Baseline to 21 days post EEN completion]
Association of fermentable carbohydrates intake with concentration of short chain fatty acids in stool
Crohn's Disease activity score [Baseline to 21 days post EEN completion]
Comparison of weighted Paediatric Crohn's Disease Activity Index score between the two groups (minimum score: 0, maximum: 125). Higher score indicates higher disease activity severity.
Blood inflammatory markers [Baseline to 21 days post EEN completion]
Comparison of concentration of blood inflammatory cytokines between the two groups
Quality of life [Baseline to 21 days post EEN completion]
Comparison of IMPACT III scores between the two groups (minimum score: 35, maximum: 135). Higher scores indicate better quality of life.

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Newly diagnosed or relapsing patients with active CD, who have shown clinical improvement by the 4th week of EEN treatment

Exclusion Criteria:

Administration of another induction treatment (e.g. corticosteroids, biologic agents).
Lack of clinical improvement with EEN treatment, as assessed by the clinical team.
Enrolment in other studies investigating the efficacy of novel therapies for maintenance or induction of remission.
Patients or families unable to provide written consent for participation in the study.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	University Hospital Crosshouse	Crosshouse	United Kingdom	KA2 0BE
2	Royal Hospital for Sick Children	Edinburgh	United Kingdom	EH9 1LF
3	Royal Hospital for Children	Glasgow	United Kingdom	G51 4TF
4	Forth Valley Royal Hospital	Larbert	United Kingdom	FK5 4WR
5	University Hospital Wishaw	Wishaw	United Kingdom	ML2 0DP

Sponsors and Collaborators

NHS Greater Glasgow and Clyde
University of Glasgow

Investigators

Principal Investigator: Richard K Russell, MBChB, MRCP, MRCPCH, PhD, NHS Greater Glasgow and Clyde
Principal Investigator: Konstantinos Gerasimidis, PhD, MSc, BSc, FHEA, University of Glasgow