Crohn Disease
Conditions
Keywords
Inflammatory Bowel Disease, Gastroenteritis, Gastrointestinal Diseases, Digestive System Diseases, Intestinal Diseases
Brief summary
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
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.
Interventions
DIETARY_SUPPLEMENTPartial Enteral Nutrition
Dietary intervention (Liquid food replacement intervention)
Sponsors
University of Glasgow
NHS Greater Glasgow and Clyde
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Crohn's Disease Activity Index | Baseline to 52 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Steroid-free remission | Baseline to 52 weeks | Comparison of steroid-free remission rates between the two groups. |
| Body weight | Baseline to 12 weeks | Comparison of body weight (kg) between the two groups. |
| Body fat mass | Baseline to 12 weeks | Comparison of body fat mass (percent, %) measured with Bioelectrical Impedance Analysis between the two groups. |
| Body fat-free mass | Baseline to 12 weeks | Comparison of body fat-free mass (percent, %) measured with Bioelectrical Impedance Analysis between the two groups. |
| Handgrip strength | Baseline to 12 weeks | Comparison of handgrip strength measured with handgrip strength dynamometer between the two groups. |
| Blood immunophenotype | Baseline to 12 weeks | 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. |
| Harvey-Bradshaw Index | Baseline to 52 weeks | 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\] |
| Faecal Calprotectin | Baseline to 12 weeks | Comparison of faecal calprotectin levels between the two groups. Higher scores indicate worse outcomes. |
| Blood C-Reactive Protein | Baseline to 12 weeks | Comparison of blood C-reactive protein levels between the two groups. Abnormal values indicate worse outcomes. |
| Blood Erythrocyte Sedimentation Rate | Baseline to 12 weeks | Comparison of blood erythrocyte sedimentation rates between the two groups. Abnormal values indicate worse outcomes. |
| Blood Albumin | Baseline to 12 weeks | Comparison of blood albumin levels between the two groups. Abnormal values indicate worse outcomes. |
| Blood Haemoglobin | Baseline to 12 weeks | Comparison of blood haemoglobin levels between the two groups. Abnormal values indicate worse outcomes. |
| Dosage of biologics | Baseline to 52 weeks | Comparison of biologics dose prescribed between the two groups. |
| Blood anti-drug antibodies | Baseline to 12 weeks | Comparison of blood anti-drug antibodies between the two groups. |
| Blood adalimumab | Baseline to 12 weeks | Comparison of blood levels of adalimumab (drug) between the two groups. |
| Micronutrient status | Baseline to 12 weeks | Comparison of micronutrient status measured by NHS laboratories as standard care of treatment between the two groups. Abnormal values indicate worse outcomes. |
| Self-Administered Inflammatory Bowel Disease Questionnaire | Baseline to 12 weeks | Comparison of Self-Administered Inflammatory Bowel Disease Questionnaire (SIBDQ) scores (range: 10-70) between the two groups. Higher SIBDQ scores indicate better outcomes. |
| Body Mass Index | Baseline to 12 weeks | Comparison of Body Mass Index (BMI) (kg/m2) between the two groups. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 3-day estimated food diary with food photography | Baseline to 6 weeks | Comparison of prospective dietary intake measured with 3-day estimated food diaries with the assistance of food photography between subgroups of patients. |
| EPIC-NORFOLK Food Frequency Questionnaire | Baseline | 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. |
| Gut microbiome function | Baseline to 12 weeks | Comparison of gut microbiome function measured with various targeted and untargeted bacterial metabolites (e.g. GC/LC-MS) between subgroups of patients. |
| Gut microbiome composition | Baseline to 12 weeks | Comparison of gut microbiome composition measured with 16S rRNA sequencing and shotgun metagenomics between subgroups of patients. |
Countries
United Kingdom
Contacts
Primary ContactAleksandra Jatkowska, BSc (Hons)
Backup ContactBernadette E White, MBio (Hons)
Outcome results
None listed