Biologics and Partial Enteral Nutrition Study

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Crohn Disease

Intervention / Treatment
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* Dietary Supplement: Partial Enteral Nutrition


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Partial Enteral Nutrition<br>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<br>* Dietary intervention (Liquid food replacement intervention)<br>|
| No Intervention: Unrestricted diet<br>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?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Inflammatory Bowel Disease, Gastroenteritis, Gastrointestinal Diseases, Digestive System Diseases, Intestinal Diseases