Combining Nutritional Therapy and Anti-TNFα Treatment in Pediatric Patients With Crohn's Disease

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:

1. 3-day diet record (3DDR) - Completed by both arms at weeks 1, 12, 24 and 52 to assess dietary intake differences and dietary adherence to mCDED. 2. 24-hour diet recall - Conducted by a dietitian to assess dietary adequacy of both groups at weeks 1, 2 (for intervention group only), 6, 12, and 24. 3. CDED diet habits questionnaire - Completed by both groups at weeks 1 and 52 to assess how their diet aligns with the mCDED and to evaluate any changes in dietary habits. 4. CDED adherence questionnaire - Completed by the intervention group only at weeks 2, 6, 12, and 24. 5. KIDMED questionnaire (Mediterranean Diet Quality Index in children) - Completed by both groups at weeks 1 and 52 to assess adherence to a healthy diet and good dietary habits.

7\) Paediatric Yorkhill Malnutrition Score (PYMS) - At pre-randomization assessment, weeks 24 and 52, to assess malnutrition.

8\) Clinical and Biochemical Data - Weighted paediatric Crohn's disease activity index (wPCDAI), physician global assessment (PGA), C-reactive protein (CRP), ESR (Erythrocyte Sedimentation Rate), Fecal calprotectin (FCP) and hematological data (Complete Blood Count \[CBC\]) collected at pre-randomization assessment, weeks 1, 6, 12, 24 and 52.

9\) Anthropometric data (body mass index \[BMI\], growth velocity) - Assessed over study at pre-randomization assessment, weeks 1, 2, 6, 12, 24, 36 and 52.

10\) Nutritional status (Albumin, Ferritin, B12, Vitamin D levels) - Measured in blood at weeks 1, 6, 12, 24 and 52 11) IFX trough levels - Measured in blood at weeks 6, 12, 24 and 52. 12) Optional blood sample - Participants will have the option to provide a blood sample during the pre-randomization assessment for genetic testing to investigate genetic variants that may influence response to IFX, including but not limited to HLADQA1\*05 (major histocompatibility complex, class II, DQ alpha 1).

13\) Magnetic Resonance Elastography (MRE) - Performed at Baseline (within 4 months prior to randomization and starting therapy) and at week 52 (±4 weeks) and/or when clinically indicated to assess disease activity.

14\) Intestinal ultrasound (IUS) - Performed at Baseline (T-2, within 4 months prior to randomization and starting therapy), weeks 12 (±2 weeks), 24 (±4 weeks) and 52 (±4 weeks) to assess disease activity (transmural intestinal inflammation).

15\) Colonoscopy - At Baseline (within 4 months prior to randomization and starting therapy) and at week 52 (±4 weeks) to assess disease activity (SES-CD; Simple endoscopic score for Crohn's disease). While not mandatory, it is highly encouraged. In the absence of a colonoscopy, a composite score will be generated. If a colonoscopy is performed, mucosal washes and intestinal biopsies will be collected for research purpose.

16\) Fecal samples - Collected without preservatives by participants at weeks 1, 2, 6, 12, 24, and 52 for longitudinal microbiota analysis, in vitro microbiota culturing, and fecal transplantation into germ-free recipient mice.

17\) IMPACT-III - Quality of life survey completed by all participants at weeks 1, 12 and 52.

• Steroid-free clinical and biochemical remission at week 12 in participants receiving mCDED alongside IFX compared with participants receiving IFX alone. [Срок оценки: 12 weeks]
• Steroid-free clinical and biochemical response at weeks 24 and 52 in participants receiving mCDED alongside IFX compared with participants receiving IFX alone. [Срок оценки: 24 and 52 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. [Срок оценки: 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. [Срок оценки: Week 52]
• Endoscopic response and endoscopic remission at week 52 in participants receiving mCDED alongside infliximab (IFX) compared with participants receiving IFX alone. [Срок оценки: Week 52]
• 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. [Срок оценки: Week 52]
• Long-term dietary habits in participants receiving dietary therapy, including consumption of ultra-processed foods (UPFs) and adherence to healthy dietary patterns. [Срок оценки: Week 52]
• Association between ongoing adherence to reduced ultra-processed food (UPF) consumption and long-term biologic response. [Срок оценки: Week 52]
• Microbial changes induced by the dietary intervention and their association with clinical and biochemical response. [Срок оценки: Weeks 12, 24 and 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. [Срок оценки: Week 12]