Biologics and Partial Enteral Nutrition Study (BIOPIC)

Combining Partial Enteral Nutrition With Biologics to Optimise Induction and Maintenance Therapy for Adults With Active Ileocolonic Crohn's Disease

Crohn's disease (CD) is a chronic, incurable condition associated with inflammation in the gut lining. It causes diarrhoea, severe abdominal pain, poor nutrition and adversely affects the quality of life of sufferers. Two of the best treatments currently used in people with CD are drug injections and/or infusions (biologics), and a liquid-only diet using specialised milkshakes. However, treatment with biologics is only successful in approximately 40% of the patients, and although treatment with the liquid-only diet has a better safety and effectiveness profile, it is difficult for patients to stick to this as their sole source of nutrition for 6-8 weeks, particularly for adults. BIOPIC study aims to investigate whether replacing half of a habitual diet with specialised milkshakes will improve response to standard treatment with biologics in adults with CD.

Study Overview

• Status: Recruiting
• Conditions: Crohn Disease
• Intervention / Treatment: Dietary supplement: Partial Enteral Nutrition

Detailed Description

80 adult patients with active CD who are due to start biologic injections therapy with adalimumab as part of their standard of care for the first time will be recruited for this study. Patients will be randomly allocated to replace either half of their normal diet with nutritionally complete milkshakes or to follow their usual diet for 6 weeks. The investigators will compare the proportion of patients whose symptoms and disease markers will improve between the two groups at 6 and 12 weeks, and how many of them will remain symptoms-free for up to a year following treatment. The investigators will also explore whether the half-liquid diet will influence patients' nutrition and quality of life. Last, the investigators will investigate if gut bacteria changes and their metabolites associate with patients' eating habits and their responses to treatment with biologics.

The primary aim of the BIOPIC study is to investigate if replacement of 50% of habitual food intake with a proprietary liquid diet for 6 weeks will improve remission rates at 12 weeks in adult patients with active ileocolonic CD treated with first-line biologics (TNFα antagonists, adalimumab) as their standard treatment of care. The secondary aim is to investigate if replacement of 50% of habitual food intake with a proprietary liquid diet for 6 weeks will prolong remission in adult patients with active ileocolonic CD treated with first-line biologics (TNFα antagonists) as their standard treatment of care.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Aleksandra Jatkowska, BSc (Hons); Phone Number: 07743585420; Email: a.jatkowska.1@research.gla.ac.uk
• Study Contact Backup: Name: Bernadette E White, MBio (Hons); Phone Number: 07719607863; Email: b.white.1@research.gla.ac.uk

Study Locations

• United Kingdom
  • Glasgow, United Kingdom, G12 0YN
    • Recruiting
    • Gartnavel General Hospital
    • Contact: Jonathan C MacDonald, BM (Hons), BSc (Hons), FRCP
  • Glasgow, United Kingdom, G42 9LF
    • Recruiting
    • The New Victoria Hospital
    • Contact: Jonathan C MacDonald, BM (Hons), BSc (Hons), FRCP
  • Scotland
    • Glasgow, Scotland, United Kingdom, G31 2ER
      • Recruiting
      • Glasgow Royal Infirmary
      • Contact: Daniel R Gaya, MBChB (Hons), FRCP, MSc, MD
    • Glasgow, Scotland, United Kingdom
      • Recruiting
      • Queen Elizabeth University Hospital
      • Contact: John P Seenan, MBChB (Hons), FRCP, MRCP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Eligible participants are all adults (≥16 years old) with active CD (defined as Crohn's Disease Activity Index ≥ 150) who are due to initiate standard adalimumab (TNFα antagonist) induction treatment (160 mg day 0, 80 mg at 2 weeks and then 40 mg every 2 weeks).

Exclusion Criteria:

• Inability to provide written consent to participate in the study
• Pregnant and/or breastfeeding individuals
• Presence of stoma
• Presence of short bowel syndrome
• Previous treatment with an anti-TNFα inhibitor
• Use of any other biologic therapy or oral small molecule therapy within the last 12 weeks
• Patients currently receiving oral or intravenous steroids at a dosage >20mg/day prednisolone or >9mg budesonide
• Introduction of or change in dose of immunomodulator (azathioprine, mercaptopurine, methotrexate) within the past 8 weeks
• Use of oral antibiotics within the past 4 weeks
• CD with a major fistulising or symptomatic fibrotic stricturing phenotype
• Patients tested positive for blood-borne viruses such as HIV and Hepatitis
• 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Partial Enteral Nutrition; Patients allocated to Partial Enteral Nutrition study arm will be asked to replace 50% of their daily energy requirements with a proprietary formula (Modulen IBD, Nestle) for 6 weeks alongside standard care of treatment with adalimumab as induction therapy.	Dietary supplement: Partial Enteral Nutrition; Dietary intervention (Liquid food replacement intervention)
NO_INTERVENTION: Unrestricted diet; Patients allocated to unrestricted diet study arm will be asked to follow their normal diet for 6 weeks alongside standard care of treatment with adalimumab as induction therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Crohn's Disease Activity Index	Comparison of Crohn's Disease Activity Index (CDAI) score (approximate range: 0-600) between the intervention (PEN) and control group (unrestricted diet). Higher CDAI scores indicate worse outcomes. Clinical response is defined as baseline CDAI score decrease of ≥ 70, and clinical remission is defined as CDAI score <150.	Baseline to 52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Harvey-Bradshaw Index	Comparison of Harvey-Bradshaw Index (HBI) score (approximate range: 0-50) between the intervention (PEN) and control group (unrestricted diet). Higher HBI scores indicate worse outcomes. Clinical response is defined as baseline HBI score decrease of ≥ 3, and clinical remission is defined as score <5]	Baseline to 52 weeks
Faecal Calprotectin	Comparison of faecal calprotectin levels between the two groups. Higher scores indicate worse outcomes.	Baseline to 12 weeks
Blood C-Reactive Protein	Comparison of blood C-reactive protein levels between the two groups. Abnormal values indicate worse outcomes.	Baseline to 12 weeks
Blood Erythrocyte Sedimentation Rate	Comparison of blood erythrocyte sedimentation rates between the two groups. Abnormal values indicate worse outcomes.	Baseline to 12 weeks
Blood Albumin	Comparison of blood albumin levels between the two groups. Abnormal values indicate worse outcomes.	Baseline to 12 weeks
Blood Haemoglobin	Comparison of blood haemoglobin levels between the two groups. Abnormal values indicate worse outcomes.	Baseline to 12 weeks
Steroid-free remission	Comparison of steroid-free remission rates between the two groups.	Baseline to 52 weeks
Dosage of biologics	Comparison of biologics dose prescribed between the two groups.	Baseline to 52 weeks
Blood anti-drug antibodies	Comparison of blood anti-drug antibodies between the two groups.	Baseline to 12 weeks
Blood adalimumab	Comparison of blood levels of adalimumab (drug) between the two groups.	Baseline to 12 weeks
Micronutrient status	Comparison of micronutrient status measured by NHS laboratories as standard care of treatment between the two groups. Abnormal values indicate worse outcomes.	Baseline to 12 weeks
Blood immunophenotype	Comparison of immunophenotype profiles (characterisation of immune cells) measured with flow cytometry immunophenotyping between the two groups. Higher levels of specific pro-inflammatory cells indicate worse outcomes.	Baseline to 12 weeks
Self-Administered Inflammatory Bowel Disease Questionnaire	Comparison of Self-Administered Inflammatory Bowel Disease Questionnaire (SIBDQ) scores (range: 10-70) between the two groups. Higher SIBDQ scores indicate better outcomes.	Baseline to 12 weeks
Body Mass Index	Comparison of Body Mass Index (BMI) (kg/m2) between the two groups.	Baseline to 12 weeks
Body weight	Comparison of body weight (kg) between the two groups.	Baseline to 12 weeks
Body fat mass	Comparison of body fat mass (percent, %) measured with Bioelectrical Impedance Analysis between the two groups.	Baseline to 12 weeks
Body fat-free mass	Comparison of body fat-free mass (percent, %) measured with Bioelectrical Impedance Analysis between the two groups.	Baseline to 12 weeks
Handgrip strength	Comparison of handgrip strength measured with handgrip strength dynamometer between the two groups.	Baseline to 12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut microbiome composition	Comparison of gut microbiome composition measured with 16S rRNA sequencing and shotgun metagenomics between subgroups of patients.	Baseline to 12 weeks
Gut microbiome function	Comparison of gut microbiome function measured with various targeted and untargeted bacterial metabolites (e.g. GC/LC-MS) between subgroups of patients.	Baseline to 12 weeks
3-day estimated food diary with food photography	Comparison of prospective dietary intake measured with 3-day estimated food diaries with the assistance of food photography between subgroups of patients.	Baseline to 6 weeks
EPIC-NORFOLK Food Frequency Questionnaire	Comparison of retrospective dietary intake measured with 130-item EPIC-NORFOLK Food Frequency Questionnaire between subgroups of participants. Higher consumption/avoidance of specific food groups/products might indicate better outcomes.	Baseline

Collaborators and Investigators

• Sponsor: NHS Greater Glasgow and Clyde
• Collaborators: University of Glasgow

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 20, 2021
• Primary Completion (ANTICIPATED): September 1, 2026
• Study Completion (ANTICIPATED): September 1, 2026

Study Registration Dates

• First Submitted: April 15, 2021
• First Submitted That Met QC Criteria: April 23, 2021
• First Posted (ACTUAL): April 26, 2021

Study Record Updates

• Last Update Posted (ACTUAL): November 30, 2021
• Last Update Submitted That Met QC Criteria: November 29, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Inflammatory Bowel Disease; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: GN21RH169

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