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

Overview

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

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.

Interventions

• 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.
• Other continuation of current therapy
  continuation of current maintenance medical therapy for ulcerative colitis

Primary outcome measures

• Number of individuals with sustained biochemical remission [Time frame: Baseline, 12 months]
• Number of individuals with sustained sonographic remission [Time frame: Baseline, 12 months]
• Number of individuals with sustained clinical remission [Time frame: Baseline, 12 months]
• Number of individuals with sustained endoscopic remission [Time frame: Baseline, 12 months]

Secondary outcome measures (10)

• Proportion of individuals maintaining corticosteroid-free remission [Time frame: 12 months]
• Change in host metabolites in states of deep remission [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: Month 24]

Eligibility criteria

Inclusion criteria

• Consenting patients aged 18 to 75 years with an established diagnosis of ulcerative colitis (UC) for at least 3 years.
• 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.
• Patients in clinical, biochemical (fecal calprotectin <100), radiologic and endoscopic remission since the last colonoscopy.

Exclusion criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Other

Study locations

United States · 1 center

• University of Chicago — Chicago

Identifiers

NCT: NCT06693310 · IRB24-0008

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗