Efficacy and Safety of CDED With Anti-TNF-α Biologics in Crohn's Disease: A Randomized Trial

Sun Yat-sen University

Status: Not yet enrolling

Conditions: Crohn's Disease；Mucosal Healing；Dietary Intervention

Treatments: Other: Crohn's Disease Exclusion Diet

Study type: Interventional

Funder types: Other

Identifiers

NCT07344428

2021ZSLYEC-127-CDED

Details and patient eligibility

About

Crohn's disease (CD) is a chronic inflammatory bowel disease with high recurrence and surgical rates. Mucosal healing is a key therapeutic goal, yet current anti-TNF-α biologics achieve only about 30% mucosal healing. Dietary intervention, particularly the Crohn's Disease Exclusion Diet (CDED), shows promise in CD management. Preliminary data suggest that combining CDED with anti-TNF-α biologics may significantly improve mucosal healing rates (42.9% vs 25%). This single-center, prospective, randomized, controlled trial will enroll 185 adult CD patients with active disease (SES-CD ≥3), randomly assigned 1:1 to receive either anti-TNF-α biologics plus CDED or anti-TNF-α biologics alone. The primary endpoint is mucosal healing rate at week 14 (SES-CD=0). Secondary endpoints include clinical remission, endoscopic response, transmural healing, and adverse events. This study aims to provide high-quality evidence for the efficacy and safety of this combined approach in Chinese CD patients.

Full description

Crohn's disease (CD) is a chronic granulomatous inflammatory disease that can affect the entire digestive tract, characterized by a protracted course and complex complications. Although the advent of biologics has significantly improved CD treatment outcomes, real-world data show that only about 30% of patients achieve mucosal healing with anti-TNF-α biologics (infliximab or adalimumab), representing a major therapeutic bottleneck. According to the international STRIDE-II consensus, mucosal healing is a key target in CD treat-to-target strategy and is closely associated with better long-term prognosis. In recent years, the role of dietary factors in CD management has gained increasing attention. Exclusive enteral nutrition (EEN) has demonstrated efficacy in inducing remission and mucosal healing in pediatric CD, but poor long-term adherence limits its application in adults. Based on this, oral dietary regimens mimicking EEN components (such as the Crohn's Disease Exclusion Diet, CDED) have become a new research focus. Preliminary data from our research team showed that compared to anti-TNF-α biologics alone, CDED combined with anti-TNF-α biologics resulted in significantly higher mucosal healing rates (42.9% vs 25.0%) and greater improvement in SES-CD scores at week 14, providing strong preliminary evidence for this combined approach to overcome the efficacy bottleneck.This is a single-center, prospective, randomized, open-label, controlled clinical trial conducted at the Inflammatory Bowel Disease Center, Department of Gastroenterology, Sixth Affiliated Hospital of Sun Yat-sen University. A total of 185 eligible adult Chinese patients with active CD will be enrolled and randomly assigned in a 1:1 ratio using SAS-generated random sequences with sealed envelope allocation concealment. The intervention group will receive standardized anti-TNF-α biologic therapy (infliximab 5mg/kg IV at weeks 0, 2, 6, and 14, or adalimumab subcutaneous injection at standard doses) combined with strict CDED. The dietary protocol includes detailed electronic and paper recipes specifying allowed grains (rice only), vegetables (avoiding nightshades), fruits, meats (recommended fish and poultry, limited red meat), oils (olive oil, coconut oil), and cooking methods (steaming, boiling, blanching), while strictly prohibiting ultra-processed foods, nuts, legumes, and butter. Patients will maintain daily food diaries via WeChat group and shared documents, with frequent supervision and guidance from researchers. The control group will receive the same anti-TNF-α biologic therapy alone without dietary intervention. The primary endpoint is mucosal healing rate at week 14 (defined as SES-CD score=0). Secondary endpoints include clinical remission rate (CDAI<150), endoscopic response rate (≥50% reduction in SES-CD), transmural healing rate (assessed by intestinal ultrasound), and adverse event incidence. Sample size calculation is based on preliminary data with superiority test assumption and 20% dropout rate. Data analysis will follow intention-to-treat (ITT) principle using SPSS 25.0 software.This study is innovative as it is the first in China to use a rigorous randomized controlled trial design to validate whether a specific, easily implementable, and cost-effective dietary intervention (CDED) can synergistically enhance the efficacy of standard biologic therapy, aiming to overcome the limitation of suboptimal mucosal healing rates with biologics alone. The findings are expected to provide high-level evidence for long-term dietary management in CD patients, forming a dietary intervention guidance program with Chinese characteristics, thereby improving patient outcomes and reducing healthcare burden.

Enrollment: 185 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:1.Age: Aged ≥18 years.2.Diagnosis: Diagnosis of Crohn's disease confirmed by endoscopy and histopathology, with active disease (CDAI ≥150).3.Treatment Indication: Indicated for anti-TNF-α biologic therapy (infliximab or adalimumab) and being naive to these specific agents.4.Informed Consent: Willing and able to provide written informed consent.5.Compliance: Able to understand and comply with the study protocol requirements, including dietary intervention and follow-up schedule.

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Exclusion Criteria:1.Severe Complications: Presence of intestinal obstruction, intra-abdominal abscess, intestinal fistula, or other severe complications requiring surgical intervention.2.Comorbidities: Severe cardiac, hepatic, or renal insufficiency (e.g., Child-Pugh class C, or eGFR <30 mL/min/1.73 m²).3.Infection Risk: Active tuberculosis, active hepatitis B, HIV infection, or other severe opportunistic infections.4.Malignancy: Current or history of malignancy, except for non-melanoma skin cancer.5.Pregnancy Status: Pregnant or breastfeeding women, or women planning pregnancy during the study period.6.Medication Use: Recent use (within 3 months) of other immunosuppressants (e.g., azathioprine, methotrexate) or corticosteroids (e.g., prednisone >20 mg/day).7.Dietary Restrictions: Severe food allergies, celiac disease, severe malnutrition (BMI <18.5 kg/m²), or inability to adhere to the Crohn's Disease Exclusion Diet (CDED).8.Other Factors: Concurrent participation in another clinical trial, or any other condition deemed by the investigator to make the patient unsuitable for study participation.

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Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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185 participants in 2 patient groups

Crohn's Disease Exclusion Diet + Anti-TNF-α biologics

Experimental group

Description:

Participants in this group will receive anti-TNF-α biologics (infliximab 5mg/kg IV at weeks 0, 2, 6, and 14, or adalimumab subcutaneous injection at standard doses) combined with the Crohn's Disease Exclusion Diet (CDED). The CDED protocol includes detailed dietary guidance specifying allowed foods (rice, certain vegetables and fruits, fish, poultry, olive oil) and prohibited items (ultra-processed foods, nuts, legumes, butter). Patients will maintain daily food diaries and receive frequent supervision and guidance from researchers to ensure dietary compliance.

Treatment:

Other: Crohn's Disease Exclusion Diet

Anti-TNF-α biologics only

No Intervention group

Description:

Participants in this group will receive anti-TNF-α biologics alone (infliximab 5mg/kg IV at weeks 0, 2, 6, and 14, or adalimumab subcutaneous injection at standard doses) without any dietary intervention. This group serves as the control to evaluate the additional benefit of CDED when combined with standard biologic therapy. No specific dietary restrictions or guidance will be provided to this group.