Neurophenotype Predicts CD Disease Progression

Multimodal MRI-based Neurophenotype Reflecting Brain-gut Interactions to Predict Intestinal Disease Progression in Patients With Crohn's Disease

The goal of this observational study is aimed to develop a novel multimodal neuroimaging-based model to characterize the neurophenotype of Crohn's Disease patients and assess its ability for predicting disease progression, using multiomics data to interpret the model.

Participants will be followed-up of at least six months for patients without disease progression to assess the relationship between neurophenotype and intestinal outcomes.

Study Overview

• Status: Recruiting
• Conditions: Radiomics; Multi-omics
• Intervention / Treatment: Diagnostic test: Logistic regression (LR) prediction models

Detailed Description

Brain-gut axis plays a crucial role in the pathogenesis of Crohn's disease (CD); however, CD neurophenotype and its impact on intestinal disease progression remain unclear. We aimed to develop a novel multimodal neuroimaging-based model to characterize the neurophenotype of CD patients and assess its ability for predicting disease progression, using multiomics data to interpret the model. This study enrolled CD patients who underwent baseline testing (including neuroimaging, psychological scales, MR enterography, and ileocolonoscopy) and faecal/blood samples collection. The neurophenotypes of patients were characterized using a neuroimaging-based model. The predictive ability of neurophenotype model for disease progression was evaluated using Cox regression analysis. Multiomics data (including faecal microbiome, faecal/blood metabolomics, intestinal permeability, blood-brain-barrier permeability, and blood neurotransmitter levels) were used to elucidate how neurophenotypes reflect brain-gut interactions.

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Xuehua Li; Phone Number: 13580364103; Email: lxueh@mail.sysu.edu.cn
• Study Contact Backup: Name: Ruonan Zhang; Phone Number: 15124748450; Email: zhangrn25@mail2.sysu.edu.cn

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • XploreMET v3.0 system
    • Contact: Xuehua Li

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

This study included adult patients aged 18 to 45 with Crohn's disease (CD) who were admitted to the First Affiliated Hospital of Sun Yat-sen University between May 2021 and June 2025.

Description

Inclusion Criteria:

• (a) CD patients aged 18-45 years; (b) the completion of multimodal brain MRI and administration of psychological questionnaires; (c) MR enterography (MRE), ileocolonoscopy, and blood or faecal samples, collection within one week of brain MRI; (d) a follow-up of at least six months for patients without disease progression; and (e) right-handedness.

Exclusion Criteria:

• (a) recent use of antibiotics, probiotics, or prebiotics within three months prior to inclusion; (b) history of neurosurgery, cerebrovascular disease, or brain trauma; (c) use of central nervous system drugs or antidepressants within three months prior to inclusion; (d) identification of brain lesions on MR scan; (e) claustrophobia; or (f) presence of metal implants.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Crohn's disease patients with no-to-mild inflammation; On MR enterography, the Magnetic Resonance Index of Activity (MaRIA) and Magnetic Resonance Enterography Global Score (MEGS) were used to characterize intestinal inflammation by assessing intramural and extramural lesions in both the small and large intestines. In ileocolonoscopy, the Simplified Endoscopic Activity Score for Crohn's Disease (SES-CD) was used to quantify mucosal or luminal lesions from the terminal ileum to the colorectum. Both modalities were used to classify patients with no-to-mild or moderate-to-severe inflammation. We defined patients as having moderate-to-severe inflammation when at least two of the following criteria were met: (1) MaRIA≥11; (2) MEGS≥ 10 for the small bowel or MEGS≥12 for the colon; or (3) SES-CD≥11. Otherwise, patients were categorized as having no-to-mild inflammation.	Diagnostic test: Logistic regression (LR) prediction models; Logistic regression model was used to establish a model to distinguish different levels of intestinal inflammation.
Crohn's disease patients with moderate-to-severe inflammation; On MR enterography, the Magnetic Resonance Index of Activity (MaRIA) and Magnetic Resonance Enterography Global Score (MEGS) were used to characterize intestinal inflammation by assessing intramural and extramural lesions in both the small and large intestines. In ileocolonoscopy, the Simplified Endoscopic Activity Score for Crohn's Disease (SES-CD) was used to quantify mucosal or luminal lesions from the terminal ileum to the colorectum. Both modalities were used to classify patients with no-to-mild or moderate-to-severe inflammation. We defined patients as having moderate-to-severe inflammation when at least two of the following criteria were met: (1) MaRIA≥11; (2) MEGS≥ 10 for the small bowel or MEGS≥12 for the colon; or (3) SES-CD≥11. Otherwise, patients were categorized as having no-to-mild inflammation.	Diagnostic test: Logistic regression (LR) prediction models; Logistic regression model was used to establish a model to distinguish different levels of intestinal inflammation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The area under the ROC curve (AUC) to assess the performance of diagnostic model	After baseline brain MRI scanning, patients were followed up.	6 months

Collaborators and Investigators

• Sponsor: First Affiliated Hospital, Sun Yat-Sen University
• Investigators: Principal Investigator: Xuehua Li, Sun Yat-sen University First Affiliated Hospital Department of Radiology

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2021
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: June 5, 2024
• First Submitted That Met QC Criteria: June 5, 2024
• First Posted (Actual): June 11, 2024

Study Record Updates

• Last Update Posted (Actual): June 11, 2024
• Last Update Submitted That Met QC Criteria: June 5, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Magnetic Resonance Imaging; Crohn's disease; Abdominal MRI; Brain/gut interaction
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Disease Progression
• Other Study ID Numbers: 82070680

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Disclosure is subject to application

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No