Multimodal Ultrasound in Inflammatory Bowel Diseases (CELESTIAL)

Prospective Study to Evaluate the Role of Contrast-enhanced Ultrasound (CEUS) and Elastography in Predicting Clinical and Endoscopic Remission (Deep Remission) in Inflammatory Bowel Disease

The role of intestinal ultrasound in treatment monitoring has recently gained increasing interest thanks to its non-invasiveness, cost-effectiveness and largely availability. Moreover, new ultrasonographic tools, particularly dynamic contrast-enhanced ultrasound (D-CEUS) and shear wave elastography (SWE) can provide further useful information, such as a quantitative estimation of bowel intramural microvacularization and tissue stiffness.

Aim of this study is to evaluate the role of D-CEUS and SWE in predicting deep remission at 12 months from treatment induction in IBD.

Study Overview

• Status: Recruiting
• Conditions: Inflammatory Bowel Diseases
• Intervention / Treatment: Diagnostic test: Multimodal ultrasound

Detailed Description

Background: Clinical remission is no more considered an appropriate therapeutic target for Inflammatory Bowel Diseases (IBD) and other parameters such as endoscopic and transmural remission are now recognized as prognostic factors ("deep remission"). Correctly monitoring treatment response is crucial to rapidly adequate therapeutic algorithms avoiding complications. The role of intestinal ultrasound in treatment monitoring has recently gained increasing interest thanks to its non-invasiveness, cost-effectiveness and largely availability. Moreover, new ultrasonographic tools, particularly dynamic contrast-enhanced ultrasound (D-CEUS) and shear wave elastography (SWE) can provide further useful information, such as a quantitative estimation of bowel intramural microvacularization and tissue stiffness.

Primary objective: to evaluate the role of D-CEUS and SWE in predicting deep remission at 12 months from treatment induction in IBD.

Secondary objectives:

• To evaluate the relationship between clinical activity and CEUS/elastography parameters
• To evaluate the relationship between endoscopic activity and CEUS/elastography parameters
• To evaluate the relationship between inflammation indices and CEUS/elastography

Exploratory aims:

• To evaluate the relationship between CEUS/elastography parameters and serum biomarkers of fibrosis
• To evaluate the relationship between CEUS/elastography parameters and faecal microbiota in a subset of patients Study design: Prospective, interventional, single-center study. Methods: 50 consecutive patients with Crohn's disease or Ulcerative Colitis needing to begin biologic treatment according to international guidelines and with an affected intestinal segment detectable in B-mode ultrasound will be enrolled in the Unit of Internal Medicine and Gastroenterology of the Policlinico Gemelli. Exclusion criteria will be induction of biologic therapy in prophylaxis after surgery in Crohn's disease, lack of visualization of affected intestinal tract (eg. obesity), diagnosis of undetermined colitis, hearth failure, known allergy to ultrasound contrast agents, pregnancy and lactation. Colonoscopies, blood tests and ultrasound evaluations (B-mode ultrasound, elastography and CEUS) will be performed as per normal clinical practice. Data obtained from these procedures will be recorded and analyzed specifically for the study. The only study-specific procedures are the collection of fecal samples for microbiota evaluation, urine samples for metabolomics evaluation and an additional blood sample for evaluation of fibrosis biomarkers, both collected at the time of recruitment. The additional blood sample will be taken from the same peripheral venous access route used for blood sampling in normal clinical practice. Ileal elastography and CEUS will be performed before starting treatment and after 2/3, 8 and 16 weeks, 6 months, 12 months, 24 months and 36 months. If indicated by clinical assessment, some patients will be re-evaluated after 3 weeks. Clinical assessment will include Harvey-Bradshaw index or Mayo score, blood cell count, CRP and ESR, as per clinical practice. An additional blood sampling will be done for fibrosis biomarker evaluation. In particular, we will do multiple analysis (Bio-Plex, Biorad ) for IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, Eotaxin, basic FGF, G-CSF, GM-CSF, IFN-g, IP-10, MCP-1, MIP-1a, PDGF-bb, MIP-1b, RANTES, TNF-a, VEGF, TL -1a, TGF-b, IL-33, ST2. Data about the clinical outcome (i.e. surgery, hospitalizations, need for steroids…) and biomarkers of fibrosis will be collected up to 36 months after the start of the study.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Maria Assunta Zocco; Phone Number: 00393470597805; Email: mariaassunta.zocco@policlinicogemelli.it

Study Locations

• Italy
  • Roma, Italy, 00168
    • Recruiting
    • Fondazione Policlinico Gemelli IRCCS
    • Contact: MARIA ASSUNTA ZOCCO, PhD; Phone Number: 00393470597805

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• written informed consent
• diagnosis of Crohn's disease or Ulcerative Colitis
• indication to start biologic treatment according to international guidelines
• affected intestinal segment detectable in B-mode ultrasound

Exclusion Criteria:

• induction of biologic therapy in prophylaxis after surgery in Crohn's disease
• lack of visualization of affected intestinal tract (eg. obesity)
• diagnosis of undetermined colitis
• hearth failure
• known allergy to ultrasound contrast agents
• pregnancy
• lactation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients; patients with Crohn's disease or Ulcerative Colitis needing to begin biologic treatment	Diagnostic test: Multimodal ultrasound; Contrast enhanced ultrasound and shear wave elastography on target intestinal loop are perfomed before and at different timepoints after treatment induction

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
predicting treatment response	to quantify peak enhancement intensity in Arbitray Units AU (measured by analysing D-CEUS time-intensity curves) in patients with inflammatory bowel diseases undergoing biological treatment, stratified according to 12-months response to treatment (responders vs non-responders)	12 months after treatment induction

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
predicting treatment response	to quantify the other D-CEUS parameters (measured by analysing D-CEUS time-intensity curves) in patients with inflammatory bowel diseases undergoing biological treatment, stratified according to 12-months response to treatment (responders vs non-responders)	12 months after treatment induction
predicting treatment response	to quantify mean intestinal loop stiffness (measured by shear wave elastography) in patients with inflammatory bowel diseases undergoing biological treatment, stratified according to 12-months response to treatment (responders vs non-responders)	12 months after treatment induction

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2019
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: March 16, 2023
• First Submitted That Met QC Criteria: August 3, 2023
• First Posted (Actual): August 14, 2023

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 3, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Intestinal Diseases
• Other Study ID Numbers: 2743

Drug and device information, study documents

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