Biologics and Paediatric Enteral Nutrition in Crohn's Disease Study (BIOPIC-Kids)

Biologics and Paediatric Enteral Nutrition in Crohn's Disease Study (BIOPIC-Kids): Combining Enteral Nutrition With Biologics to Optimise Induction and Maintenance Therapy for Children With Active Crohn's Disease

Crohn's disease (CD) is a chronic, incurable condition associated with gut inflammation. Two important treatments currently used to manage CD are special drug injections (biologics) or a liquid-only diet using specialised milkshakes. However, treatment with biologics is only successful in approximately 55-60%. The liquid-only diet also has a better safety and effectiveness profile than traditional treatments like steroids. However, gut inflammation often returns not long after the normal diet is re-introduced, and it is difficult for patients to stick to as their sole source of nutrition for 6-8 weeks.

The BIOPIC-Kids study aims to investigate whether replacing the normal diet with specialised milkshakes for 6 weeks improves response to treatment and maintenance of remission with biologics in children and young adults with CD. To achieve this, children and young adults (aged 6-18 years) with active CD commencing biologics as standard of care treatment will be randomly allocated to follow their normal diet OR replace varying amounts of their normal diet with specialised milkshakes for 6 weeks. Participants not wanting to be randomised can choose the group of their preference. Patients starting a liquid-only diet OR biologics alongside a liquid-only diet as standard of care treatment will also be recruited to compare different treatment outcomes.

Study Overview

• Status: Recruiting
• Conditions: Crohn's Disease (CD)
• Intervention / Treatment: Dietary supplement: enteral nutrition

Detailed Description

90 Paediatric patients with active Crohn's disease (CD) who are due to start standard of care treatment with TNF alpha (TNFα) inhibitors infliximab(IFX) or adalimumab(ADA) will be recruited from six centres across Scotland for this study. Participants will be randomised, or allocated by their choice, to either follow their unrestricted diet or a liquid diet (enteral nutrition) that replaces varying amounts of their unrestricted diet for the first 6 weeks of IFX/ADA induction therapy. Observational cohorts receiving standard of care treatment with exclusive enteral nutrition (EEN therapy) or IFX/ADA alongside adjuvant EEN therapy will be recruited to compare the outcomes of different treatments.

The investigators will compare the proportion of patients whose symptoms and disease markers will improve between the groups following 10-12 weeks of induction therapy, and how many of them will remain symptoms-free for up to a year following treatment. The study will also explore whether the study's liquid diet will influence patient's nutrition, body composition and quality of life. Additionally, host immunophenotype, inflammatory cytokines and the gut and oral microbiome, including composition and function will be explored.

The primary aim of this study is to investigate if replacement of the habitual diet with varying amounts of enteral nutrition for 6 weeks in total, will improve rates of clinical remission and normalisation of biomarkers of mucosal healing in children and young adults with active CD receiving biologic therapy with TNFα inhibitors compared to children with active CD receiving biologic therapy and consuming their habitual, unrestricted diet. The secondary aim of this study is to investigate if the nutritional regime above will reduce risk of secondary loss of treatment response, and of subsequent disease relapse.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Konstantinos Gerasimidis, Professor; Phone Number: +441419560580; Email: Konstantinos.Gerasimidis@glasgow.ac.uk
• Study Contact Backup: Name: Sophie F Morris, BSc (Hons); Phone Number: +447887804802; Email: s.morris.2@research.gla.ac.uk

Study Locations

• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZG
    • Not yet recruiting
    • The Royal Aberdeen Children's Hospital
    • Contact: Iain S Chalmers, MBChB; Email: iain.chalmers@nhs.scot
  • Crosshouse, United Kingdom, KA2 0BE
    • Not yet recruiting
    • University Hospital Crosshouse
    • Contact: Lawrence Armstrong, MBCHB, MRCPCH; Email: Lawrence.Armstrong@aapct.scot.nhs.uk
  • Dundee, United Kingdom, DD1 9SY
    • Not yet recruiting
    • Ninewells Hospital
    • Contact: Richard Hansen, MBChB, PhD, FRCPCH, FRCP Edin; Email: richard.hansen2@nhs.scot
  • Edinburgh, United Kingdom, EH16 4TJ
    • Recruiting
    • Royal Hospital for Children & Young People
    • Contact: Richard K Russell, MBChB, MRCP, MRCPCH, PhD; Email: Richard.Russell@nhs.scot
  • Glasgow, United Kingdom, G51 4TF
    • Recruiting
    • Royal Hospital For Children
    • Contact: Lisa Gervais, MSc; Email: Lisa.Gervais2@nhs.scot
  • Wishaw, United Kingdom, ML2 0DP
    • Not yet recruiting
    • University Hospital Wishaw
    • Contact: Thomas J Jordan, MBBS, BSc; Email: Thomas.Jordan@lanarkshire.scot.nhs.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Eligible participants to the RCT are children or young adults (aged 6 to 18 years old) who have active CD (defined as a weighted paediatric Crohn's disease Activity Index score (wPCDAI) ≥ 12.5 or a Faecal Calprotectin level >250 mg/kg and who have a clinical indication to initiate standard of care induction treatment with TNFα inhibitors (infliximab or adalimumab).
• Eligible participants to the observational cohorts are children or young adults (aged 6 to 18 years old) who have active CD (defined as a weighted paediatric Crohn's disease Activity Index score (wPCDAI) ≥ 12.5 or a Faecal Calprotectin level >250 mg/kg and who are due to initiate standard of care induction treatment with EEN therapy alongside TNFα inhibitors (infliximab or adalimumab) or standard of care induction treatment with EEN therapy without TNFα inhibitors (infliximab or adalimumab)

Exclusion Criteria:

• Inability to provide consent to participate in the study (i.e., this applies to young adults (aged 16-18 years) who are old enough but unable to provide consent and carers (of children aged 6-15 years old) who are unable to provide consent on behalf of their child).
• Presence of stoma or of short bowel syndrome.
• Patients currently receiving oral or intravenous steroids at a dosage >20mg/day prednisolone or >9mg/day budesonide.
• Patients who start another induction therapy (e.g., high dosage of steroids) or change the dose of background immunomodulator (azathioprine, mercaptopurine, methotrexate) within the past 4 weeks.
• CD with a major fistulising or symptomatic fibrotic stricturing phenotype.
• Patients with comorbid anorexia nervosa.
• Any clinical contraindication to use of exclusive enteral nutrition or partial enteral nutrition.
• Patients tested positive for blood-borne viruses such as HIV and Hepatitis B and C.
• Patients with untreated tuberculosis (latent or active).
• Current enrolment in other studies of an investigational product or dietary intervention.
• Food allergies, which do not permit participation in the study (e.g., cow's milk allergy).
• Pregnant and/or breastfeeding individuals.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Enteral Nutrition; Paediatric patients allocated to the enteral nutrition study arm will be asked to replace varying amounts of their daily energy requirements with a proprietary formula (Ready-To-Drink Modulen, Nestle, or Modulen IBD, Nestle) for 6 weeks alongside standard of care treatment with infliximab or adalimumab as induction therapy.	Dietary supplement: enteral nutrition; Dietary intervention: a liquid food replacement intervention involving replacing varying amounts of energy requirements with a nutritionally complete liquid formula.
No Intervention: Unrestricted Diet; Paediatric patients allocated to the unrestricted diet study arm will be asked to follow their habitual, unrestricted diet for 6 weeks alongside standard of care treatment with infliximab or adalimumab as induction therapy.
No Intervention: Exclusive Enteral Nutrition; An observational cohort of paediatric patients receiving standard of care treatment with exclusive enteral nutrition as induction therapy.
No Intervention: Exclusive enteral nutrition alongside Infliximab or Adalimumab Induction Therapy; An observational cohort of paediatric patients receiving standard of care treatment with exclusive enteral nutrition alongside infliximab or adalimumab as induction therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Faecal Calprotectin	The primary outcome of this study is to compare the proportion of patients who show normalisation of Faecal Calprotectin (FCAL) levels between the intervention (enteral nutrition) and control group (unrestricted diet). Normalisation of FCAL is defined as < 100 mg/kg.	Baseline to 10-12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight Paediatric Crohn's Disease Activity Index	Comparison of Weighted Paediatric Crohn's Disease Activity Index (wPCDAI) score (approximate range: 0-125) between the intervention (enteral nutrition) and control group (unrestricted diet). Higher wPCDAI scores indicate worse outcomes. Clinical response is defined as baseline wPCDAI decrease of ≥ 17.5, and clinical remission is defined as CDAI score <12.5.	Baseline to 10-12 Weeks
Faecal Calprotectin	Comparison of faecal calprotectin levels between the groups. Higher scores indicate worse outcomes.	Baseline to 10-12 weeks
Blood C-Reactive Protein	Comparison of blood C-reactive protein levels between the groups. Abnormal values indicate worse outcomes.	Baseline to 10-12 weeks
Blood Erythrocyte Sedimentation Rate	Comparison of blood erythrocyte sedimentation rates between the groups. Abnormal values indicate worse outcomes.	Baseline to 10-12 weeks
Blood Albumin	Comparison of blood albumin levels between the groups. Abnormal values indicate worse outcomes.	Baseline to 10-12 weeks
Blood Haemoglobin	Comparison of blood haemoglobin levels between the two groups. Abnormal values indicate worse outcomes.	Baseline to weeks 10-12
Steroid-Free Remission	Comparison of steroid-free remission rates between the groups	Baseline to 52 weeks (+/-2 weeks)
Dosage of biologics	Comparison of cumulative dosage of biologics required to enter in clinical remission and maintain therapeutic drug levels between the groups treated with biologics as standard of care treatment.	Baseline to 52 weeks (+/- 2 weeks)
Blood anti-drug antibodies	Comparison of blood anti-drug antibodies between the groups of patients on standard of care biologic therapy.	Week 6 to 52 weeks (+/- 2 weeks)
Blood Infliximab or Adalimumab	Comparison of trough levels of infliximab or adalimumab (drug) in blood between the groups receiving standard of care treatment with biologics	Week 6 to 52 weeks (+/- 2 weeks)
Health-related quality of life	Comparison of health-related quality of life (using the IMPACT-III questionnaire) between the groups (minimum score: 35, maximum: 175). Higher scores indicate better quality of life.	Baseline to 10-12 Weeks
Body Mass Index (BMI)	Comparison of Body Mass Index (BMI) (kg/m2) between the groups	Baseline to 10-12 weeks
Body Weight	Comparison of body weight (kg) between the groups	Baseline to 10-12 weeks
Body Composition (Total Body water, Body Fat Mass, Body Fat Free Mass)	Comparison of total body water (percent, %), body fat mass (percent, %) and body fat-free mass (percent, %) with bioelectrical impedance analysis and the deuterium oxide dilution method.	Baseline to 10-12 weeks
Paediatric Yorkhill Malnutrition Score (PYMS)	Comparison of Paediatric Yorkhill Malnutrition Score (PYMS) between the groups. Minimum score: 0; maximum score: 7. Scores of 0 indicate low risk of malnutrition, scores of 1 indicate a medium risk of malnutrition and scores of 2 or above indicates a high risk of malnutrition.	Baseline to 10-12 weeks
Handgrip strength	Comparison of handgrip strength measured with handgrip strength dynamometer between the groups	Baseline to 10-12 weeks
Micronutrient blood levels (vitamin A)	Comparison of blood vitamin A levels (µmol/L) between the groups	Baseline to 10-12 weeks
Micronutrient Blood Levels (Vitamin B1)	Comparison of blood Vitamin B1 levels (ng/g Hb) between the groups	Baseline to 10-12 weeks
Micronutrient Blood Levels (Vitamin B2)	Comparison of blood Vitamin B2 levels (nmol/g Hb) between the groups	Baseline to 10-12 weeks
Micronutrient Blood Levels (Vitamin B6)	Comparison of blood Vitamin B6 levels (pmol/g Hb) between the groups	Baseline to 10-12 weeks
Micronutrient Blood Levels (Vitamin B12)	Comparison of blood vitamin B12 levels (pmol/L) between groups.	Baseline to 10-12 weeks
Micronutrient Blood Levels (Vitamin C)	Comparison of blood Vitamin C levels (umol/L) between the groups	Baseline to 10-12 weeks
Micronutrient Blood Levels (Vitamin D)	Comparison of blood Vitamin D levels (mmol/L) between the groups	Baseline to 10-12 weeks
Micronutrient Blood Levels (Vitamin E)	Comparison of blood Vitamin E levels (µmol/mmol of cholesterol) between the groups	Baseline to 10-12 weeks
Micronutrient Blood Levels (Vitamin K)	Comparison of blood Vitamin K levels (nmol/mmol triglyceride) between the groups	Baseline to 10-12 weeks
Micronutrient Blood Levels (Folate)	Comparison of blood folate levels (ug/L) between the groups	Baseline to 10-12 weeks
Micronutrient Blood Levels (zinc)	Comparison of blood zinc levels (µmol/L) between the groups	Baseline to 10-12 weeks
Micronutrient Blood Levels (Magnesium)	Comparison of blood magnesium levels (mmol/L) between the groups	Baseline to 10-12 weeks
Micronutrient Blood Levels (Copper)	Comparison of blood copper levels (µmol/L between the groups	Baseline to 10-12 weeks
Micronutrient blood levels (Selenium)	Comparison of blood selenium levels (µmol/L) between the groups	Baseline to 10-12 weeks
Micronutrient blood levels (Ferritin)	Comparison of blood ferritin levels (µg/L) between the groups	Baseline to 10-12 weeks
Dietary Habits	Comparison of dietary habits between patients with Crohn's disease and healthy controls (using a child appropriate food frequency questionnaire (FFQ)	Baseline
Acceptability of EN feeds Questionnaires	Comparison of acceptability of EN feeds between groups of participants receiving either the study's liquid diet or standard of care EEN using acceptability questionnaires developed by the research team as non-validated tools designed to gauge participants' acceptability and opinion of the EN feeds. These consist of a series of 9-point hedonic scales representing the degree to which participants like or dislike different sensory attributes of the EN feeds (e.g., taste, smell etc.,). Approximate score range: 5 - 45. Higher scores indicate a higher preference for the EN feed. An additional section included asks participants to rank their overall preference of the EN feeds from 1 to 4 (1= the product liked best and 4= the product liked the least). A lower ranking indicates the EN feed liked best.	Baseline to week 6 or completion of standard of care EEN
Adherence to EN feeds Questionnaires	Comparison of adherence to EN between groups of participants receiving either the study's liquid diet or standard of care EEN using adherence questionnaires developed by the research team as non-validated tools designed to assess participants' adherence to their liquid diet. The questionnaires consist of yes/no questions or 5-point scales representing the degree to which participants did adhere or did not adhere to different aspects of their liquid diet (1: Always (>95% of the time); 2: Often (80% of the time); 3: Half of the time (50% of the time); 4: Rarely (20% of the time) and 5: Never (<5% of time)). A score of 42 indicates highest adherence and a score of 18 indicates lowest adherence.	Baseline to week 6 or completion of standard of care EEN

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut and oral microbiome composition	Comparison of gut microbiome composition measured with 16S rRNA sequencing and shotgun metagenomics between subgroups of participants with Crohn's disease and healthy controls	Baseline to 10-12 weeks
Gut and oral microbiome function	Comparison of gut microbiome function measured with various targeted and untargeted bacterial metabolites (e.g. LC-MS/NMR) between subgroups of participants with Crohn's disease and healthy controls	Baseline to 10-12 weeks
Associations between dietary intake and response to TNFα inhibitors	Exploration of associations between dietary intake and response to TNFα inhibitors in a joint analysis including all Crohn's disease patients receiving receiving standard of care biologics.	Baseline to week 10-12
Blood Immunophenotype and inflammatory cytokines	Comparison of the effects of different induction therapies on immunophenotype profiles (characterisation of immune cells) measured with flow cytometry immunophenotyping between the groups	Baseline to week 10-12

Collaborators and Investigators

• Sponsor: University of Glasgow
• Collaborators: NHS Lothian; NHS Tayside; NHS Grampian; NHS Lanarkshire; NHS Greater Clyde and Glasgow; NHS Ayrshire and Arran

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2026
• Primary Completion (Estimated): August 1, 2030
• Study Completion (Estimated): August 1, 2030

Study Registration Dates

• First Submitted: March 24, 2026
• First Submitted That Met QC Criteria: April 3, 2026
• First Posted (Actual): April 13, 2026

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Crohn's Disease; Combination Therapy; Infliximab; Adalimumab; Paediatric; Biologic Therapy; Exclusive Enteral Nutrition; Partial Enteral Nutrition
• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Crohn Disease; Therapeutics; Nutrition Therapy; Feeding Methods; Nutritional Support; Enteral Nutrition
• Other Study ID Numbers: BIOPIC-KIDS; IRAS 353897 (Other Identifier: HRA)

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 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