STOP-UC: De-escalation of Therapy in Patients With Ulcerative Colitis With Histological Remission

The goal of this study is to better understand treatment strategies for people with ulcerative colitis (UC). Researchers will compare patients with UC in histologic remission (no evidence of inflammation or active disease on endoscopy and biopsies) who continue to take medical therapy to patients with UC who de-escalate (decrease or discontinue) medical therapy. Both treatment strategies are considered within regular medical practice. Researchers want to find out whether remission can be maintained after de-escalation of therapy.

Participants will be:

• either be randomly assigned to continue medical therapy or de-escalate medical therapy -OR- be assigned per the participant's preference
• clinically managed according to regular medical care
• asked to provide blood, stool (poop), and tissue samples for study purposes

Study Overview

• Status: Recruiting
• Conditions: Ulcerative Colitis (UC)
• Intervention / Treatment: Other: continuation of current therapy; Other: de-escalation or discontinuation of therapy

Detailed Description

This is a prospective, partially-randomized, patient-preference clinical trial conducted at a tertiary academic center [University of Chicago Medicine Inflammatory Bowel Disease (IBD) Center]. Patients in clinical, biochemical, and endoscopic remission with biopsies showing histologic quiescence or normalization will be identified and approached after consultation with their IBD care team.

Subjects will be given a choice to either de-escalate their therapy (de-escalation group) or continue their current therapy (control group). This study design is to enhance the feasibility and real-world applicability. By permitting participants with strong preferences to choose their assigned strategy, we anticipate higher enrollment and retention among eligible subjects who might otherwise decline participation. Participants without a clear preference will be randomized 1:1 to de-escalation versus continuation, thereby preserving the integrity of comparative analyses. This approach enhances generalizability, respects patient autonomy, and mirrors clinical decision-making in routine clinical practice while maintaining methodological rigor.

After enrollment, participants will be monitored for 24 months. After the 24-month period, participants who remain in remission will continue 5 years of longitudinal data collection from routine clinical care.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Research Coordinator; Phone Number: 215-596-9715; Email: Alex.Mathew@bsd.uchicago.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago
      • Principal Investigator: David T Rubin, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Consenting patients aged 18 to 75 years with an established diagnosis of ulcerative colitis (UC) for at least 3 years.

2. Patients in deep remission, defined by the absence of endoscopic and histologic signs of active inflammation (i.e. histological normalization or histological quiescence) in all biopsies obtained during colonoscopy, within the last 12 months.

   • If the most recent colonoscopy is within the last 3 years and demonstrates normalized/quiescent pathology findings (i.e., patient is in stable remission), the patient would not be expected to undergo yearly colonoscopies. Therefore, a persistent normalized calprotectin test will be accepted as sufficient to define deep remission with no change in therapy.
3. Patients in clinical, biochemical (fecal calprotectin <100), radiologic and endoscopic remission since the last colonoscopy.

Exclusion Criteria:

1. Any noted active inflammation [clinical, sonographic, biochemical, endoscopic (in any colonic segment)].
2. Patients with any changes in therapy after colonoscopy showing histological normalization or quiescence.
3. Corticosteroid use after colonoscopy showing histologic normalization or quiescence.
4. Patients with any noted history of primary sclerosing cholangitis or invisible or unresected high-grade dysplasia (suspected or confirmed).
5. Pregnancy or actively trying to conceive
6. Inability to follow the proposed sample collection and monitoring protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control group; continuation of current therapy	Other: continuation of current therapy; continuation of current maintenance medical therapy for ulcerative colitis
Active Comparator: de-escalation group; de-escalation or discontinuation of therapy	Other: de-escalation or discontinuation of therapy; De-escalation of therapy, defined as a step-down from maintenance with advanced therapy (biologic or synthetic small molecule) to oral aminosalicylate-based therapy or complete discontinuation of therapy if they are allergic or intolerant to aminosalicylate-based therapy. If patients are receiving immunomodulator or oral aminosalicylate maintenance therapy, they will be de-escalated to complete discontinuation of therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of individuals with sustained biochemical remission	Biochemical remission defined as fecal calprotectin (FCP) level less than 150 and C-reactive protein (CRP) level less than the predetermined normal range according to the test manufacturer (typically less than 5.0mg/dL).	Baseline, 12 months
Number of individuals with sustained sonographic remission	Sonographic remission defined as bowel wall thickness (BWT) less than 4 millimeters(mm) in rectum and BWT less than 3 mm in the remainder of the bowel; measured by intestinal ultrasound	Baseline, 12 months
Number of individuals with sustained clinical remission	Clinical remission defined as Patient-Reported Outcome (PRO-2) score less than 1. The PRO-2 questionnaire measures patient-reported stool frequency and rectal bleeding in UC; scores range from 0-3, with higher scores indicating more severe symptoms.	Baseline, 12 months
Number of individuals with sustained endoscopic remission	Endoscopic remission defined as Mayo endoscopic subscore equal to 0 or 1. The Mayo endoscopic subscore is a physician-reported measure of mucosal appearance at endoscopy. Scores range from 0-3, with higher scores indicating more disease activity.	Baseline, 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of individuals maintaining corticosteroid-free remission	Calculated by dividing the number of individuals maintaining remission without the need for corticosteroid medications by the total number of individuals in the study	12 months
Change in host metabolites in states of deep remission	Measured by mass spectrometry, flow cytometry, enzyme-linked immunosorbent assay (ELISA)-based assays and/or real-time polymerase chain reaction (RT-PCR)-based assays	Baseline, at the time points when deep remission is clinically confirmed (expected at scheduled assessments at 6, 12, 18, and 24 months)
Change in microbial metabolites in states of deep remission	Quantitative measurement of host metabolites using mass spectrometry, flow cytometry, enzyme-linked immunosorbent assays (ELISA), and/or real-time polymerase chain reaction (RT-PCR)-based assays to characterize biochemical changes associated with deep remission	Baseline, at the time points when deep remission is clinically confirmed (expected at scheduled assessments at 6, 12, 18, and 24 months)
Change in host metabolites in states of disease relapse	Measured by mass spectrometry, flow cytometry, ELISA-based assays and/or RT-PCR-based assays	Baseline, at the time points when deep remission is clinically confirmed (expected at scheduled assessments at 6, 12, 18, and 24 months)
Change in microbial metabolites in states of disease relapse	Measured by mass spectrometry, flow cytometry, ELISA-based assays and/or RT-PCR-based assays	Baseline, at the time points when deep remission is clinically confirmed (expected at scheduled assessments at 6, 12, 18, and 24 months)
Change in microbial composition in states of deep remission	Measured by mass spectrometry and RT-PCR-based assays	Baseline, at the time points when deep remission is clinically confirmed (expected at scheduled assessments at 6, 12, 18, and 24 months)
Change in microbial abundance in states of deep remission	Measured by RT-PCR-based assays	Baseline, at the time points when deep remission is clinically confirmed (expected at scheduled assessments at 6, 12, 18, and 24 months)
Change in microbial composition in states of disease relapse	Measured by RT-PCR-based assays	Baseline, at the time points when deep remission is clinically confirmed (expected at scheduled assessments at 6, 12, 18, and 24 months)
Change in microbial abundance in states of disease relapse	Measured by RT-PCR-based assays	Baseline, at the time points when deep remission is clinically confirmed (expected at scheduled assessments at 6, 12, 18, and 24 months)
Number of individuals with long-term remission	Remission defined as an individual with all of the following: Clinical remission: PRO-2 less than 1; Biochemical remission: FCP less than 150, CRP less than 1.0 mg/dL; Sonographic remission: BWT ultrasound assessment less than 4mm in Rectum; less than 3mm in remainder of Bowel; Endoscopic remission: Mayo Endoscopic Subscore equals 0 or 1	Month 24

Collaborators and Investigators

• Sponsor: University of Chicago
• Investigators: Principal Investigator: David T Rubin, MD, University of Chicago

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2025
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: November 7, 2024
• First Submitted That Met QC Criteria: November 14, 2024
• First Posted (Actual): November 18, 2024

Study Record Updates

• Last Update Posted (Actual): April 6, 2026
• Last Update Submitted That Met QC Criteria: April 3, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: histological remission; de-escalation of therapy
• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: IRB24-0008

Drug and device information, study documents

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