Therapy De-escalation for Ulcerative Colitis

Overseen By Research Coordinator

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Chicago

Must not be taking: Corticosteroids

Disqualifiers: Active inflammation, Primary sclerosing cholangitis, Dysplasia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how individuals with ulcerative colitis (UC) in deep remission can manage their treatment. Researchers will compare those who either reduce or stop their medication to those who continue with their current treatment. The goal is to determine if remission can be maintained with less medication. This trial may suit individuals who have had UC for at least three years and have been free from inflammation for the past year. Participants will provide blood, stool, and tissue samples as part of the study.

As an unphased trial, this study offers a unique opportunity to contribute to understanding UC management strategies.

Will I have to stop taking my current medications?

The trial involves some participants continuing their current medications while others may decrease or stop them. It doesn't specify if you must stop your medications, but you might be assigned to either group.

What prior data suggests that this treatment strategy is safe for ulcerative colitis patients?

Research has shown that patients with ulcerative colitis who have healthy tissue can remain stable after reducing or stopping their medication. One study found that adjusting treatment based on specific medication levels in the body was linked to a lower risk of disease recurrence.

However, limited information exists on safely reducing or stopping multiple medications simultaneously. Some patients believe that being in remission (having no active disease) allows them to reduce or stop treatment, but this belief varies among individuals.

Overall, evidence suggests that reducing therapy can be safe for some patients, particularly those without signs of inflammation. However, it is crucial to seek personal medical advice from healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the concept of therapy de-escalation for ulcerative colitis because it explores reducing or stopping treatment without compromising patient health. Most current treatments, like biologics or immunosuppressants, require continuous use to manage symptoms and prevent flare-ups. However, this approach aims to maintain remission with less medication, potentially minimizing side effects and lowering treatment costs. If successful, it could revolutionize how we manage long-term therapy for ulcerative colitis, giving patients a chance for a better quality of life with fewer drugs.

What evidence suggests that this trial's treatments could be effective for ulcerative colitis?

This trial will compare therapy de-escalation with the continuation of current therapy for ulcerative colitis (UC). Research has shown mixed results for reducing or stopping treatment in people with UC. About half of the patients experienced a return of symptoms within a year after stopping medications like infliximab. Some patients remained symptom-free, while others had flare-ups, and one required surgery to remove part of the colon. The decision to reduce or stop medication often depends on personal preferences and the understanding that symptoms might return. Overall, it involves balancing the reduction of medication side effects with the risk of the disease returning. ^{1 2 6 7 8}

Who Is on the Research Team?

David T Rubin, MD

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

This trial is for people with ulcerative colitis who show no signs of inflammation or active disease. They must be in histological remission, meaning their endoscopy and biopsies are clear. The study excludes details not provided.

Inclusion Criteria

My inflammatory bowel disease has been in remission for at least 6 months.

My recent tests show no signs of active inflammation in my colon.

Exclusion Criteria

My treatment changed after a colonoscopy showed my colon is now normal or inactive.

I am using corticosteroids after my colonoscopy showed normal or inactive disease.

I have a history of primary sclerosing cholangitis or dysplasia.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to either de-escalation of therapy or continuation of current therapy and monitored for 24 months

24 months

Regular visits as per clinical practice

Follow-up

Participants who remain in remission will continue 5 years of longitudinal data collection from routine clinical care

5 years

What Are the Treatments Tested in This Trial?

Interventions

• De-escalation of Therapy

Trial Overview The STOP-UC trial compares two approaches: continuing current medical therapy versus decreasing or stopping it altogether for those in remission from ulcerative colitis. Participants will be randomly placed into one of these groups.

How Is the Trial Designed?

Group I: de-escalation group Active Control 1 Intervention

de-escalation or discontinuation of therapy

Group II: Control group Active Control 1 Intervention

continuation of current therapy

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Published Research Related to This Trial

A systematic review of 83 randomized controlled trials involving 17,737 patients with ulcerative colitis revealed significant variability in the definitions of clinical response and remission, with over 50 different definitions used.

Despite advancements in trial design, there is a need for a standardized core outcome set to improve the consistency of efficacy and safety reporting in clinical trials for ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heterogeneity in Definitions of Endpoints for Clinical Trials of Ulcerative Colitis: A Systematic Review for Development of a Core Outcome Set. Ma, C., Panaccione, R., Fedorak, RN., et al.[2019]

A systematic review of seven randomized controlled trials involving biologic drugs for ulcerative colitis found no significant differences in the rate of adverse events among adalimumab, golimumab, and vedolizumab during the induction phase, and infliximab, adalimumab, golimumab, and vedolizumab during the maintenance phase.

Vedolizumab showed the most favorable safety profile during the induction phase, while infliximab was favored during the maintenance phase, suggesting that while all biologics are generally safe, some may have advantages in specific treatment phases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Profile of Biologic Drugs in the Therapy of Ulcerative Colitis: A Systematic Review and Network Meta-Analysis. Moćko, P., Kawalec, P., Pilc, A.[2018]

Anti-TNF therapies have significantly improved outcomes for patients with inflammatory bowel disease (IBD), but issues like primary failure and side effects can limit their long-term use.

New targeted therapies are emerging that may offer better safety profiles and the potential for combination treatments, but more research is needed to determine their optimal use and long-term safety in managing IBD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IBD therapeutics: what is in the pipeline? Toskas, A., Akbar, A.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6676361/

Treatment De-Escalation in Patients With Inflammatory ... In this study, approximately 50% of the patients experienced relapse within 1 year after infliximab discontinuation. Long-term outcomes of this group were ...

2. journals.lww.com journals.lww.com/ajg/fulltext/2022/10002/s1019_long_term_outcomes_of_treatment_with_and.1019.aspx

S1019 Long-Term Outcomes of Treatment With and... After de-escalation, 3 patients maintained objective remission (2 biochemical, 1 endoscopic), 3 had disease flare, of which 1 required colectomy, and 2 lacked ...

3. gastrojournal.org gastrojournal.org/article/S0016-5085(24)05537-9/fulltext

Ethical Considerations of De-intensification of Therapy in IBD In an international survey, 25% of patients equated remission with de-escalation of therapy, and 10% with stopping therapy.

4. academic.oup.com academic.oup.com/ecco-jcc/article/18/Supplement_1/i1567/7587195

P844 Frequency and effectiveness of dose de-escalation of ... The incidence rate of dose de-escalation per patient-year of follow-up was: 6% (95% confidence interval [CI]=5.8-6.2%), 9% (7.4-10.7%), 5% (1-9 ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S021057052300376X

De-escalating therapy in inflammatory bowel disease Anti-TNF discontinuation led to significantly higher relapse rates compared to IMM discontinuation in UC and CD patients on combination therapy.

6. academic.oup.com academic.oup.com/crohnscolitis360/article/7/2/otaf026/8115984

A Guide to De-escalation of Combination Therapy in ... Advanced combination therapy has seen increased use in IBD therapy; however, there is limited data on how to de-escalate these patients safely.

7. nature.com nature.com/articles/s44355-024-00005-9

Patients with ulcerative colitis who have normalized ... Patients with ulcerative colitis who have normalized histology are clinically stable after de-escalation of therapy | npj Gut and Liver.

8. gutnliver.org gutnliver.org/journal/view.html?doi=10.5009/gnl220070

De-escalation of Therapy in Patients with Quiescent ... This revealed that dose de-escalation based on trough level was associated with a decreased risk of relapse.