Biologics and Paediatric Enteral Nutrition in Crohn's Disease Study (BIOPIC-Kids): Combining Enteral Nutrition With Biologics to Optimise Induction and Maintenance Therapy for Children With Active Crohn's Disease
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 90
- 试验地点
- 6
- 主要终点
- Faecal Calprotectin
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Eligible participants to the RCT are children or young adults (aged 6 to 18 years old) who have active CD (defined as a weighted paediatric Crohn's disease Activity Index score (wPCDAI) ≥ 12.5 or a Faecal Calprotectin level >250 mg/kg and who have a clinical indication to initiate standard of care induction treatment with TNFα inhibitors (infliximab or adalimumab).
- •Eligible participants to the observational cohorts are children or young adults (aged 6 to 18 years old) who have active CD (defined as a weighted paediatric Crohn's disease Activity Index score (wPCDAI) ≥ 12.5 or a Faecal Calprotectin level >250 mg/kg and who are due to initiate standard of care induction treatment with EEN therapy alongside TNFα inhibitors (infliximab or adalimumab) or standard of care induction treatment with EEN therapy without TNFα inhibitors (infliximab or adalimumab)
排除标准
- •Inability to provide consent to participate in the study (i.e., this applies to young adults (aged 16-18 years) who are old enough but unable to provide consent and carers (of children aged 6-15 years old) who are unable to provide consent on behalf of their child).
- •Presence of stoma or of short bowel syndrome.
- •Patients currently receiving oral or intravenous steroids at a dosage >20mg/day prednisolone or >9mg/day budesonide.
- •Patients who start another induction therapy (e.g., high dosage of steroids) or change the dose of background immunomodulator (azathioprine, mercaptopurine, methotrexate) within the past 4 weeks.
- •CD with a major fistulising or symptomatic fibrotic stricturing phenotype.
- •Patients with comorbid anorexia nervosa.
- •Any clinical contraindication to use of exclusive enteral nutrition or partial enteral nutrition.
- •Patients tested positive for blood-borne viruses such as HIV and Hepatitis B and C.
- •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).
- •Pregnant and/or breastfeeding individuals.
研究组 & 干预措施
Enteral Nutrition
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.
干预措施: enteral nutrition (Dietary Supplement)
Unrestricted Diet
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
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
An observational cohort of paediatric patients receiving standard of care treatment with exclusive enteral nutrition alongside infliximab or adalimumab as induction therapy.
结局指标
主要结局
Faecal Calprotectin
时间窗: Baseline to 10-12 weeks
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.
次要结局
- Weight Paediatric Crohn's Disease Activity Index(Baseline to 10-12 Weeks)
- Faecal Calprotectin(Baseline to 10-12 weeks)
- Blood C-Reactive Protein(Baseline to 10-12 weeks)
- Blood Erythrocyte Sedimentation Rate(Baseline to 10-12 weeks)
- Blood Albumin(Baseline to 10-12 weeks)
- Blood Haemoglobin(Baseline to weeks 10-12)
- Steroid-Free Remission(Baseline to 52 weeks (+/-2 weeks))
- Dosage of biologics(Baseline to 52 weeks (+/- 2 weeks))
- Blood anti-drug antibodies(Week 6 to 52 weeks (+/- 2 weeks))
- Blood Infliximab or Adalimumab(Week 6 to 52 weeks (+/- 2 weeks))
- Health-related quality of life(Baseline to 10-12 Weeks)
- Body Mass Index (BMI)(Baseline to 10-12 weeks)
- Body Weight(Baseline to 10-12 weeks)
- Body Composition (Total Body water, Body Fat Mass, Body Fat Free Mass)(Baseline to 10-12 weeks)
- Paediatric Yorkhill Malnutrition Score (PYMS)(Baseline to 10-12 weeks)
- Handgrip strength(Baseline to 10-12 weeks)
- Micronutrient blood levels (vitamin A)(Baseline to 10-12 weeks)
- Micronutrient Blood Levels (Vitamin B1)(Baseline to 10-12 weeks)
- Micronutrient Blood Levels (Vitamin B2)(Baseline to 10-12 weeks)
- Micronutrient Blood Levels (Vitamin B6)(Baseline to 10-12 weeks)
- Micronutrient Blood Levels (Vitamin B12)(Baseline to 10-12 weeks)
- Micronutrient Blood Levels (Vitamin C)(Baseline to 10-12 weeks)
- Micronutrient Blood Levels (Vitamin D)(Baseline to 10-12 weeks)
- Micronutrient Blood Levels (Vitamin E)(Baseline to 10-12 weeks)
- Micronutrient Blood Levels (Vitamin K)(Baseline to 10-12 weeks)
- Micronutrient Blood Levels (Folate)(Baseline to 10-12 weeks)
- Micronutrient Blood Levels (zinc)(Baseline to 10-12 weeks)
- Micronutrient Blood Levels (Magnesium)(Baseline to 10-12 weeks)
- Micronutrient Blood Levels (Copper)(Baseline to 10-12 weeks)
- Micronutrient blood levels (Selenium)(Baseline to 10-12 weeks)
- Micronutrient blood levels (Ferritin)(Baseline to 10-12 weeks)
- Dietary Habits(Baseline)
- Acceptability of EN feeds Questionnaires(Baseline to week 6 or completion of standard of care EEN)
- Adherence to EN feeds Questionnaires(Baseline to week 6 or completion of standard of care EEN)
研究者
Dr Konstantinos Gerasimidis
Professor of Clinical Nutrition
University of Glasgow