Open-Label Multicentre Randomized Dietary Intervention Study in Pediatric Crohn's Disease Patients Initiating Anti-TNF Therapy
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 140
- 试验地点
- 1
- 主要终点
- Clinical and biochemical response at the first infliximab (IFX) maintenance dose (week 12) in participants receiving mCDED alongside IFX compared with participants receiving IFX alone.
研究概览
简要总结
Children with Crohn's disease (CD), a type of Inflammatory Bowel Disease (IBD), often face serious health challenges, including poor growth, frequent hospital stays, and long-term medication use. Although biologic drugs like infliximab, an anti-TNFα (Tumor necrosis factor α) medication, have improved treatment, they don't work for everyone: many children still experience symptoms or disease flare-ups. Nutritional therapies, especially the Crohn's Disease Exclusion Diet (CDED), may help improve treatment outcomes. This study will assess whether starting CDED at the same time as infliximab leads to better responses to treatment. The goal of this study is to improve how well children respond to therapy, reduce drug exposure, and support better long-term health.
详细描述
This open-label, randomized, controlled interventional study will evaluate the effectiveness of combining nutritional therapy (modified Crohn's Disease Exclusion Diet; mCDED) with infliximab (IFX) in pediatric patients with luminal Crohn's disease (CD), compared to IFX alone.
The investigators hypothesize that initiating mCDED at the start of IFX therapy will enhance clinical response by the time the first IFX maintenance dose is given (week 12), and increase clinical and biochemical remission rates at 1 year (week 52).
Participation will last up to 16 months and includes a pre-randomization phase of up to 4 months (for baseline sample and data collection), and 12 months of intervention. After randomization (T0), participants assigned to the intervention arm will follow a standardized IFX infusion schedule and begin the mCDED with the support of a dietitian. Participants in the control arm will follow the same IFX schedule and meet with a dietitian who will review their usual eating habits, but they will not be asked to follow any dietary advice.
A total of 140 pediatric CD patients (70 per arm) will be recruited from the lead site (Vancouver) and 7-9 additional participating sites (Montreal, Ottawa, Toronto, Halifax, Calgary, Edmonton, London, Hamilton) within the Canadian Children Inflammatory Bowel Disease Network (CIDsCaNN).
The following samples and data will be collected:
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
- 9 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Moderate-severe active luminal inflammatory (B1) pCD [wPCDAI > or = 40] ileal +/- colonic (L1, L2, L3), and in whom treating physician plans to start IFX
- •OR Strong suspicion of moderate-severe active luminal inflammatory (B1) pCD ileal +/- colonic (L1, L2, L3), and in whom treating physician plans to start IFX
- •Within 12-months of diagnosis (when starting IFX treatment)
- •Naïve to a biologic therapy
- •For patients with established disease who flare up: no response to dietary intervention or steroids within 4 weeks of commencement of these therapies.
- •For newly diagnosed patients: no response to dietary intervention or steroids within 2 weeks of commencement of these therapies.
- •Evidence of active inflammation: FCP level > 250 µg/g and/ or CRP > 5 mg/L or ESR > 20 mm/hr
- •BMI between the 5th and 95th percentiles, adjusted for age and sex
- •On steroids or EEN for less than 2 (or 4, for established disease) weeks
- •Able and willing to follow dietary recommendations
- •On stable dose of AZA or Methotrexate (MTX) at randomization
- •Willing to enroll in the CIDsCaNN Network study
排除标准
- •CDED, EEN, or steroids commenced more than 2 weeks prior to randomization
- •Antibiotic use in the last 2 months (except short course < 1 week between 1-2 months) or laxative use within the past month (except for bowel prep for endoscopy pre commencement of anti-TNFα)
- •Pre-, pro-, synbiotic supplements in the last month (food containing these products, e.g. yogurt, allowed)
- •Strict vegetarians and vegans
- •High risk of malnutrition as assessed by the Paediatric Yorkhill Malnutrition Score (PYMS)
- •Other known GI disorders (except IBS), food intolerances or chronic diseases
- •Bowel surgery prior the randomization
- •Severe perianal disease (fistulizing or ulcerating), fibrostenotic (B2) or penetrating (B3) disease
- •Currently on prednisone/prednisolone for > 2 weeks
- •Pregnant or breastfeeding
- •Participating in another study
- •Inability to consent
研究组 & 干预措施
IFX + mCDED
Participants will follow the modified Crohn's disease exclusion diet (mCDED) for 6 months, when initiating their infliximab therapy as part of their routine care
干预措施: IFX + mCDED (Other)
IFX
Participants will initiate their infliximab therapy as part of their routine care
结局指标
主要结局
Clinical and biochemical response at the first infliximab (IFX) maintenance dose (week 12) in participants receiving mCDED alongside IFX compared with participants receiving IFX alone.
时间窗: 12 weeks
Clinical response: defined as mild or inactive clinical disease (at least a 17.5-points decrease in weighted paediatric Crohn's disease activity index (wPCDAI) from baseline, with a score \< 40), physician global assessment (PGA) of inactive or mild disease activity, off steroids, continuation on the same anti-TNFα dose, and remaining surgery-free. Biochemical response: Defined as at least a 50% decrease in fecal calprotectin (FCP) levels compared to baseline. wPCDAI ranges from 0 to 125, with higher scores indicating greater disease activity. PGA ranges from 0 to 10, with higher scores indicating greater disease activity.
次要结局
- Endoscopic response and endoscopic remission at week 52 in participants receiving mCDED alongside infliximab (IFX) compared with participants receiving IFX alone.(Week 52)
- Steroid-free clinical and biochemical response at weeks 24 and 52 in participants receiving mCDED alongside IFX compared with participants receiving IFX alone.(24 and 52 weeks)
- Steroid-free clinical and biochemical remission at week 12 in participants receiving mCDED alongside IFX compared with participants receiving IFX alone.(12 weeks)
- Proportion of participants achieving steroid-free clinical and biochemical remission at weeks 24 and 52 in participants receiving mCDED alongside IFX compared with participants receiving IFX alone.(weeks 24 and 52)
- 1-year composite score of clinical remission and biochemical remission in addition to meeting criteria for steroid-free clinical remission adjusted for week 12 IFX trough level.(Week 52)
- Association between baseline microbiome profiles and therapeutic outcomes at the first IFX maintenance dose (week 12) using compositional analyses and machine learning (ML) approaches.(Week 12)
- Frequency of progression from inflammatory phenotype (B1) to complicated disease (B2, B3, or B2/B3) in participants receiving mCDED alongside IFX compared with participants receiving IFX alone.(Week 52)
- Long-term dietary habits in participants receiving dietary therapy, including consumption of ultra-processed foods (UPFs) and adherence to healthy dietary patterns.(Week 52)
- Association between ongoing adherence to reduced ultra-processed food (UPF) consumption and long-term biologic response.(Week 52)
- Microbial changes induced by the dietary intervention and their association with clinical and biochemical response.(Weeks 12, 24 and 52)
研究者
Kevan Jacobson
Clinical Professor
University of British Columbia