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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
90
Dietary intervention: a liquid food replacement intervention involving replacing varying amounts of energy requirements with a nutritionally complete liquid formula.
The Royal Aberdeen Children's Hospital
Aberdeen, United Kingdom
NOT_YET_RECRUITINGUniversity Hospital Crosshouse
Crosshouse, United Kingdom
NOT_YET_RECRUITINGNinewells Hospital
Dundee, United Kingdom
NOT_YET_RECRUITINGRoyal Hospital for Children & Young People
Edinburgh, United Kingdom
RECRUITINGRoyal Hospital For Children
Glasgow, United Kingdom
RECRUITINGUniversity Hospital Wishaw
Wishaw, United Kingdom
NOT_YET_RECRUITINGFaecal 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.
Time frame: Baseline to 10-12 weeks
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.
Time frame: Baseline to 10-12 Weeks
Faecal Calprotectin
Comparison of faecal calprotectin levels between the groups. Higher scores indicate worse outcomes.
Time frame: Baseline to 10-12 weeks
Blood C-Reactive Protein
Comparison of blood C-reactive protein levels between the groups. Abnormal values indicate worse outcomes.
Time frame: Baseline to 10-12 weeks
Blood Erythrocyte Sedimentation Rate
Comparison of blood erythrocyte sedimentation rates between the groups. Abnormal values indicate worse outcomes.
Time frame: Baseline to 10-12 weeks
Blood Albumin
Comparison of blood albumin levels between the groups. Abnormal values indicate worse outcomes.
Time frame: Baseline to 10-12 weeks
Blood Haemoglobin
Comparison of blood haemoglobin levels between the two groups. Abnormal values indicate worse outcomes.
Time frame: Baseline to weeks 10-12
Steroid-Free Remission
Comparison of steroid-free remission rates between the groups
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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.
Time frame: Baseline to 10-12 Weeks
Body Mass Index (BMI)
Comparison of Body Mass Index (BMI) (kg/m2) between the groups
Time frame: Baseline to 10-12 weeks
Body Weight
Comparison of body weight (kg) between the groups
Time frame: 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.
Time frame: 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.
Time frame: Baseline to 10-12 weeks
Handgrip strength
Comparison of handgrip strength measured with handgrip strength dynamometer between the groups
Time frame: Baseline to 10-12 weeks
Micronutrient blood levels (vitamin A)
Comparison of blood vitamin A levels (µmol/L) between the groups
Time frame: Baseline to 10-12 weeks
Micronutrient Blood Levels (Vitamin B1)
Comparison of blood Vitamin B1 levels (ng/g Hb) between the groups
Time frame: Baseline to 10-12 weeks
Micronutrient Blood Levels (Vitamin B2)
Comparison of blood Vitamin B2 levels (nmol/g Hb) between the groups
Time frame: Baseline to 10-12 weeks
Micronutrient Blood Levels (Vitamin B6)
Comparison of blood Vitamin B6 levels (pmol/g Hb) between the groups
Time frame: Baseline to 10-12 weeks
Micronutrient Blood Levels (Vitamin B12)
Comparison of blood vitamin B12 levels (pmol/L) between groups.
Time frame: Baseline to 10-12 weeks
Micronutrient Blood Levels (Vitamin C)
Comparison of blood Vitamin C levels (umol/L) between the groups
Time frame: Baseline to 10-12 weeks
Micronutrient Blood Levels (Vitamin D)
Comparison of blood Vitamin D levels (mmol/L) between the groups
Time frame: Baseline to 10-12 weeks
Micronutrient Blood Levels (Vitamin E)
Comparison of blood Vitamin E levels (µmol/mmol of cholesterol) between the groups
Time frame: Baseline to 10-12 weeks
Micronutrient Blood Levels (Vitamin K)
Comparison of blood Vitamin K levels (nmol/mmol triglyceride) between the groups
Time frame: Baseline to 10-12 weeks
Micronutrient Blood Levels (Folate)
Comparison of blood folate levels (ug/L) between the groups
Time frame: Baseline to 10-12 weeks
Micronutrient Blood Levels (zinc)
Comparison of blood zinc levels (µmol/L) between the groups
Time frame: Baseline to 10-12 weeks
Micronutrient Blood Levels (Magnesium)
Comparison of blood magnesium levels (mmol/L) between the groups
Time frame: Baseline to 10-12 weeks
Micronutrient Blood Levels (Copper)
Comparison of blood copper levels (µmol/L between the groups
Time frame: Baseline to 10-12 weeks
Micronutrient blood levels (Selenium)
Comparison of blood selenium levels (µmol/L) between the groups
Time frame: Baseline to 10-12 weeks
Micronutrient blood levels (Ferritin)
Comparison of blood ferritin levels (µg/L) between the groups
Time frame: 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)
Time frame: 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.
Time frame: 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.
Time frame: Baseline to week 6 or completion of standard of care EEN
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