The Intensive Post Exclusive Enteral Nutrition Study (iPENS)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Crohn Disease
• Intervention / Treatment: Other: CD-TREAT diet

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 Type: Interventional
• Enrollment (Anticipated): 58
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Konstantinos Gkikas, MSc, Bsc; Phone Number: 07759451611; Email: k.gkikas.1@research.gla.ac.uk
• Study Contact Backup: Name: Richard K Russell, MBChB, MRCP, MRCPCH, PhD; Phone Number: 01414516543; Email: richardrussell@nhs.net

Study Locations

• United Kingdom
  • Crosshouse, United Kingdom, KA2 0BE
    • Not yet recruiting
    • University Hospital Crosshouse
  • Edinburgh, United Kingdom, EH9 1LF
    • Not yet recruiting
    • Royal Hospital for Sick Children
  • Glasgow, United Kingdom, G51 4TF
    • Recruiting
    • Royal Hospital for Children
  • Larbert, United Kingdom, FK5 4WR
    • Not yet recruiting
    • Forth Valley Royal Hospital
  • Wishaw, United Kingdom, ML2 0DP
    • Not yet recruiting
    • University Hospital Wishaw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Colonic inflammation	Comparison of faecal calprotectin levels between the intervention (CD-TREAT) and the control (unrestricted diet) group	Baseline to 21 days post EEN completion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diet and faecal microbiome	Association of fermentable carbohydrates intake with relative abundance of faecal bacteria	Baseline to 21 days post EEN completion
Diet and faecal metabolome	Association of fermentable carbohydrates intake with concentration of short chain fatty acids in stool	Baseline to 21 days post EEN completion
Crohn's Disease activity score	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.	Baseline to 21 days post EEN completion
Blood inflammatory markers	Comparison of concentration of blood inflammatory cytokines between the two groups	Baseline to 21 days post EEN completion
Quality of life	Comparison of IMPACT III scores between the two groups (minimum score: 35, maximum: 135). Higher scores indicate better quality of life.	Baseline to 21 days post EEN completion

Collaborators and Investigators

• Sponsor: NHS Greater Glasgow and Clyde
• Collaborators: 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

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2020
• Primary Completion (Anticipated): January 1, 2023
• Study Completion (Anticipated): February 1, 2024

Study Registration Dates

• First Submitted: December 20, 2019
• First Submitted That Met QC Criteria: January 9, 2020
• First Posted (Actual): January 13, 2020

Study Record Updates

• Last Update Posted (Actual): July 21, 2020
• Last Update Submitted That Met QC Criteria: July 20, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: dietary intervention; food reintroduction; dietary triggers; faecal calprotectin; CD-TREAT; Exclusive enteral nutrition
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: GN19GA433P

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Participants will be asked to provide written consent for their anonymised data to be made available to public data repositories.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No