Utility of Low Intensity Pulsed Ultrasound Stimulation (LIPUS) to Modulate the Release of Mediators Capable of Reflecting the Inflammatory State in the Affected Colonic Tract of Ulcerative Colitis Patients (LIPUSinVIVO)

The goal of this clinical trial is to learn whether Low Intensity Pulsed Ultrasound (LIPUS) is capable of promoting the release of extracellular vesicles from the gut into the bloodstream of Ulcerative Colitis (UC) patients, whose content may be predictive of the inflammatory state of the mucosal source to aid the monitoring of the disease status and therapy response.

The main questions it aims to answer are:

Is LIPUS effective in inducing the release of biomarker-containing micro-vesicles into the bloodstream, capable of reflecting the inflammatory state of the mucosa during active disease?

Are there any extracellular vesicle-contained biomarkers that can monitor therapy during clinical remission?

Participants who undergo endoscopy and gut biopsy collection as per Standard Of Care, will:

• undergo abdominal ultrasound to establish the distance with the target tissue and consequently set the LIPUS device to supply the optimum energy established in the protocol.
• before LIPUS stimulation and 2 hours after stimulation, patients will have blood drawn
• an extra intestinal biopsy during endoscopy will be collected
• patients will be contacted 72h after intervention for adverse events monitoring

Study Overview

• Status: Not yet recruiting
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Device: LIPUS stimulation

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Giorgio Ferrari; Phone Number: 02 8224 2488; Email: giorgio.ferrari@hunimed.eu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

For Phase A:

• male and female patients ≥ 18 years of age (at the time of signing the Informed Consent) -signed written Informed Consent
• established diagnosis of UC with a minimum disease duration of 3 months
• moderate, moderate to severe active UC, defined by partial Mayo Score
• indication to start any targeted therapy, yet not initiated
• in case of treatment with corticosteroid: stabile dose for at least 3 weeks prior to baseline, dosage ≤ 20 mg prednisone
• indication for colonoscopy for the assessment of disease activity as for standards of care and current guidelines
• able to comply with the study procedures
• BMI <23.

For Phase B:

• male and female patients ≥ 18 years of age (at the time of signing the Informed Consent)
• signed written Informed Consent
• established diagnosis of UC and in clinical remission defined by partial Mayo Score with any targeted therapy
• able to comply with the study procedures
• BMI <23.

Exclusion Criteria for both phases:

• diagnosis of indeterminate colitis, Crohn's colitis, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis
• absolute contraindications to colonoscopy procedures, complication during previous endoscopy
• bleeding disorders
• indication for surgery for UC
• legal incapacity
• rectal topical therapy (enemas or suppositories) ≤ 2 weeks prior to baseline
• treatment with > 20 mg prednisone within 3 weeks prior to baseline
• anemia (hemoglobin < 10 g/dl) at baseline
• pregnant or breastfeeding women
• women with implanted contraceptive device
• BMI>23
• patients diagnosed with cancer (especially attention goes to colon-rectal neoplasty)
• high turnover osteoporosis
• presence of metal fragments
• joint prostheses
• varicous veins
• phlebitis and thrombophlebitis
• presence of pacemaker
• obliterating arteriopathy
• menstruation
• neoplastic tissues and surrounding areas
• tuberculosis
• individuals in the growing phase (children and adolescents)
• individuals not capable of communicating sense of pain
• any circumstances which could contradict a study participation and lead the Investigator to assess the patient as unsuitable for study participation for any other reason.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• 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: LIPUS stimulation; LIPUS stimulation supplying the pre-clinically optimized energy dosage and conditions	Device: LIPUS stimulation; Low Intensity Pulsed Ultrasound stimulation of the gut at the pre-clinically optimized conditions and energy dosage

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficiency of LIPUS in terms of target-specific extracellular vesicle release	Evaluation of LIPUS efficiency in extracellular vesicle release by measuring extracellular vesicle concentration in blood before and after LIPUS stimulation	14 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Accuracy of LIPUS stimulation in monitoring ulcerative colitis in terms of tissue state-specific biomarkers contained in LIPUS-induced extracellular vesicles	Identification of extracellular vesicle molecular content before and after LIPUS stimulation which correlate with intestinal inflammation in Ulcerative Colitis (active/remission states) by fluorescent miRNA microarray technology and RNA-seq	14 months

Collaborators and Investigators

• Sponsor: Istituto Clinico Humanitas
• Collaborators: Ospedale San Raffaele; Innovative Medicines Initiative
• Investigators: Principal Investigator: Alessandro Armuzzi, MD, Istituto Clinico Humanitas

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2024
• Primary Completion (Estimated): October 30, 2025
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: July 29, 2024
• First Submitted That Met QC Criteria: August 22, 2024
• First Posted (Actual): August 26, 2024

Study Record Updates

• Last Update Posted (Actual): August 26, 2024
• Last Update Submitted That Met QC Criteria: August 22, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: IBD-2022-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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