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| ID | Type | Description | Link |
|---|---|---|---|
| IRAS 353897 | Other Identifier | HRA |
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| Name | Class |
|---|---|
| NHS Greater Clyde and Glasgow | OTHER |
| NHS Lothian | OTHER_GOV |
| NHS Tayside | OTHER_GOV |
| NHS Grampian |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Enteral Nutrition | Experimental | 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. |
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| Unrestricted Diet | No Intervention | 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. | |
| Exclusive Enteral Nutrition | No Intervention | An observational cohort of paediatric patients receiving standard of care treatment with exclusive enteral nutrition as induction therapy. | |
| Exclusive enteral nutrition alongside Infliximab or Adalimumab Induction Therapy | No Intervention | An observational cohort of paediatric patients receiving standard of care treatment with exclusive enteral nutrition alongside infliximab or adalimumab as induction therapy. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| enteral nutrition | Dietary Supplement | Dietary intervention: a liquid food replacement intervention involving replacing varying amounts of energy requirements with a nutritionally complete liquid formula. |
| 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 |
| 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. |
| 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 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Konstantinos Gerasimidis, Professor | Contact | +441419560580 | Konstantinos.Gerasimidis@glasgow.ac.uk | |
| Sophie F Morris, BSc (Hons) | Contact | +447887804802 | s.morris.2@research.gla.ac.uk |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Royal Aberdeen Children's Hospital | Not yet recruiting | Aberdeen | AB25 2ZG | United Kingdom |
Participants will be asked to provide written consent for their anonymised data to be made available to public repositories.
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| ID | Term |
|---|---|
| D003424 | Crohn Disease |
| ID | Term |
|---|---|
| D015212 | Inflammatory Bowel Diseases |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D004750 | Enteral Nutrition |
| ID | Term |
|---|---|
| D005248 | Feeding Methods |
| D013812 | Therapeutics |
| D018529 | Nutritional Support |
| D044623 | Nutrition Therapy |
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| OTHER_GOV |
| NHS Ayrshire and Arran | OTHER |
| NHS Lanarkshire | OTHER_GOV |
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| 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 |
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 |
| University Hospital Crosshouse | Not yet recruiting | Crosshouse | KA2 0BE | United Kingdom |
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| Ninewells Hospital | Not yet recruiting | Dundee | DD1 9SY | United Kingdom |
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| Royal Hospital for Children & Young People | Recruiting | Edinburgh | EH16 4TJ | United Kingdom |
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| Royal Hospital For Children | Recruiting | Glasgow | G51 4TF | United Kingdom |
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| University Hospital Wishaw | Not yet recruiting | Wishaw | ML2 0DP | United Kingdom |
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| D007410 | Intestinal Diseases |