Crohn Disease · Ulcerative Colitis
Switching or Continuing IBD Therapy Despite Ongoing Bowel Inflammation
This study compares switching to another targeted immunomodulator with continuing current therapy in adults whose Crohn’s disease or ulcerative colitis symptoms are controlled despite moderate-to-severe bowel inflammation.
Registry title: Treat-to-Target of Endoscopic Remission in Patients With IBD in Symptomatic Remission
19 recruiting U.S. sites ↓Study at a glance
- Age
- 18 Years and older
- Treatment
- Pragmatic
- Design
- Randomized
- Central study contact
- Siddharth Singh, MD480-301-8000singh.siddharth@mayo.edu
- Sponsor
- Mayo Clinic
Research question
Among people with inflammatory bowel disease whose symptoms are controlled but whose bowel inflammation remains moderate to severe, how do switching targeted therapy and continuing current therapy compare in effectiveness and safety?
Participant snapshot
Who the study is looking for
- The study is looking for adults age 18 or older with Crohn’s disease or ulcerative colitis diagnosed at least six months ago.
- The study is looking for people in corticosteroid-free symptomatic remission according to defined patient-reported symptom measures.
- The study is looking for people with moderate-to-severe bowel inflammation shown by an eligible endoscopy or imaging test within six months before screening.
- The study is looking for people taking an approved targeted immunomodulator at a stable dose who could receive at least one alternative targeted therapy.
Participation overview
What participation may involve
Participants continue their current targeted immunomodulator or switch to another agent selected through routine care. The study follows treatment outcomes, symptoms, quality of life, treatment burden, satisfaction, and safety using questionnaires and medical-record data. What participation may involve: - Receive routine inflammatory bowel disease care while following the assigned strategy of switching or continuing targeted therapy. - Complete the two-item patient-reported outcome measure, called PRO2, at baseline and approximately every 12 weeks. - Complete questionnaires about disease control, quality of life, disability, treatment burden, and treatment satisfaction at baseline and up to three additional times. - Allow study data to be extracted from medical records at baseline and approximately every six months at minimum. Follow-up lasts 52 to 104 weeks for some participants and the full 104 weeks for others. The protocol mandates no study-specific visits. Visits follow the local standard-of-care schedule, with additional visits at the treating physician’s discretion.
Study interventions
What participants may receive or do
- Pragmatic: Participants are randomly assigned either to continue their current targeted immunomodulator or to switch, through routine care, to another guideline-supported agent chosen by the local physician and covered by the participant’s insurance formulary. Treatment may later change after relapse or intolerance at the treating team’s discretion.
Study design
How the comparison works
This is a pragmatic, multicenter, parallel-group trial that randomly assigns participants to switch targeted therapy or continue their current targeted therapy while care is delivered through routine clinical practice. Participants are randomly assigned to one of two parallel treatment strategies. The study is open-label, meaning participants and clinicians know which treatment strategy was assigned. The comparison group continues its current targeted immunomodulator and concomitant therapy. No placebo arm is listed; the study compares switching therapy with continuing current therapy.
Reported activities
Procedures and tests
- Before screening, an eligible endoscopy or imaging study must have shown moderate-to-severe bowel inflammation within the preceding six months.
- The qualifying assessment may be colonoscopy, flexible sigmoidoscopy, balloon-assisted enteroscopy, capsule endoscopy, magnetic resonance enterography, computed tomography enterography, or intestinal ultrasound.
- Participants complete the two-item patient-reported outcome measure, PRO2, at baseline and approximately every 12 weeks.
- Additional questionnaires assess inflammatory bowel disease control, quality of life, fatigue, disability, treatment burden, and medication satisfaction.
- Study information is extracted from medical records at baseline and approximately every six months at minimum.
- If a moderate-to-severe symptomatic relapse occurs, objective inflammation may be confirmed within two months using fecal calprotectin, C-reactive protein, endoscopy, enterography, or intestinal ultrasound.
Eligibility highlights
Details that may affect whether you contact the study
These are selected highlights, not a complete eligibility check. Exact criteria remain in the full registry record below.
Common requirements
- Participants must be age 18 or older; women must not be pregnant or breastfeeding.
- Crohn’s disease or ulcerative colitis must have been diagnosed at least six months earlier and confirmed by the treating provider.
- Participants must currently use an approved targeted immunomodulator for inflammatory bowel disease.
- The targeted immunomodulator dose must have been stable for at least three months before the qualifying endoscopy or imaging study.
- From the qualifying test through randomization, participants cannot escalate the targeted immunomodulator or add an immunomodulator, corticosteroid, or mesalamine; dose reduction is permitted at the provider’s discretion.
- Participants must be free of corticosteroids and in symptomatic remission according to the study’s disease-specific PRO2 symptom thresholds and the treating provider’s assessment.
- An eligible endoscopy or imaging study within six months before screening must show moderate-to-severe bowel inflammation under the study’s disease-specific definitions.
- Participants must be able to receive at least one alternative targeted immunomodulator, excluding their current one, under drug-label, clinical, and reimbursement guidelines.
Possible reasons someone may not be able to join
- People with an ostomy or ileoanal pouch are excluded.
- A serious disease other than ulcerative colitis or Crohn’s disease may exclude someone if the investigator believes it would interfere with full participation.
- A history of alcohol or drug abuse, or another health condition, may exclude someone if the investigator believes it would interfere with following study procedures.
- Anyone previously enrolled in this study is excluded.
- People with mild endoscopic disease activity are excluded when their treating provider would not consider switching targeted therapy.
Important unknowns
What the record does not make clear
- The registry says switched therapy must be covered by the participant’s insurance formulary and that no study-related medications are provided, but it does not state which care, tests, or participant costs are covered.
- The registry does not report whether participants receive compensation.
- The registry does not report whether travel, lodging, parking, or related expenses are reimbursed.
- No study-specific visits are mandated, but the registry does not explain whether questionnaires and other study activities can be completed remotely.
- A recent qualifying endoscopy or imaging study is required, but the registry does not clearly state whether additional endoscopies or imaging are required after randomization.
- The continuing group remains on concomitant therapy, and either group may start or stop inflammatory bowel disease therapies after relapse or intolerance, but the allowed background-treatment rules are not fully described.
- Corticosteroid rescue for a documented flare counts as treatment failure, and treating teams may change therapy after relapse or intolerance, but a specific rescue-treatment plan is not reported.
- The detailed description defines relapse confirmation using fecal calprotectin greater than 150 micrograms per gram, while the primary-outcome description uses greater than 250 micrograms per gram.
Before contacting the site
Questions for the study team
- How is the alternative targeted immunomodulator chosen, and what happens if my insurer does not cover the preferred option?
- Which medications, tests, and routine-care visits would the study cover, and which costs would fall to me or my insurer?
- Will I need another endoscopy or imaging test after randomization, and if so, when and why?
- What would happen to my assigned treatment and study follow-up if symptoms return, side effects occur, or I need rescue therapy?
- Can questionnaires and data collection be completed remotely, and are any in-person research activities required?
- Will I be followed for 52 weeks or 104 weeks, and when is that determined?
- Which fecal calprotectin threshold is used to confirm inflammation after a symptomatic relapse?
Before changing care
Questions for your gastroenterologist
- How stable is my disease clinically, and what does my ongoing endoscopic or imaging inflammation mean in my individual situation?
- What are the approved alternatives to my current targeted immunomodulator, and how do their risks and monitoring needs compare for me?
- Could any change to my current medicines before randomization conflict with the study’s treatment-stability requirements?
- If I consider this study, how would you coordinate routine care, monitoring, and treatment changes with the research team?
- What symptoms or test results would prompt rescue treatment or a change in therapy in my case?
This plain-language digest is provided by the Aidy clinical trials API. It may omit details and is not medical advice or an eligibility decision. Review the full registry record and confirm details with the study team.
Source record
Full registry record
The sections below preserve the study information supplied through ClinicalTrials.gov, including complete descriptions, criteria, outcomes, and locations.
About this study
The purpose of this study is to compare the effectiveness and safety of a strategy of switching to an alternative targeted immunomodulator (TIM) therapy to treat to a target of endoscopic remission, versus continuing index TIM in patients with inflammatory bowel disease (IBD) (Crohn's disease or ulcerative colitis \[UC\]) in symptomatic remission with moderate to severe endoscopic inflammation despite optimization of index TIM in a real-world setting.
This is a pragmatic, open-label, multicenter randomized control trial (RCT) conducted in asymptomatic patients with IBD who have persistent moderate to severe endoscopic inflammation despite optimization of index TIM. This study plans to recruit approximately 216 participants in the United States, who will either switching to treatment with alternative TIM to treat to a target of endoscopic remission or continue index optimized TIM. After randomization, patients will be followed prospectively within routine clinical practice for up to 2 years (104 weeks); 156 patients will be followed for the full 104 weeks, whereas 60 patients will be followed for a variable time period between 52 to 104 weeks. This trial will be conducted within select active sites in the United States and Canada The primary outcome will be time from randomization to treatment failure, as a composite of: 1. Moderate severe symptomatic relapse based on PRO2 (2-item patient reported outcome), with objective confirmation of inflammation within 2 months of event (fecal calprotectin \[FC\] \>150 mcg/g, or C reactive protein \[CRP\] \>5mg/L, or endoscopy showing moderate-severe inflammation, or magnetic resonance enterography (MRE)/computed tomography enterography (CTE)/intestinal ultrasound (IUS) showing active inflammation) with need for escalation of therapy; 2. Need for rescue therapy with corticosteroids for a documented symptomatic IBD flare; 3. IBD related hospitalization; 4. IBD-related surgery; 5. IBD-related structural complications (CD: symptomatic stricture, fistula or abscess; UC: symptomatic stricture); 6. Treatment-emergent adverse event requiring drug discontinuation. Secondary outcomes will include time from randomization to each of the components in the primary outcome, quality of life (overall quality of life, fatigue, IBD-related disability), burden of treatment (financial burden, burden of monitoring, treatment side effects), treatment satisfaction, and safety. In compliance with the pragmatic methodology of this study embedded in routine clinical care, there is no study visit mandated per study protocol. Participant visit schedules will follow local SOC with any additional visits at the treating physician's discretion. Data on all effectiveness, treatment burden and safety outcomes will be captured using a REDCap (Research Electronic Data Capture) database hosted at CCF. Data for the study will be extracted from medical record information and entered into the EDC system at baseline and then approximately every 6 months (at a minimum) thereafter, up to a 2-year follow-up period. Patient-reported outcome (PRO) measures (self-assessment questionnaires) will be utilized in this study to determine primary (efficacy) and secondary (quality of life and treatment burden and satisfaction) outcomes. Participants will complete the PRO2 at baseline and approximately every 12 weeks during the up to 2-year follow-up period; additional questionnaires (IBD-Control, PROMIS-7, Short Inflammatory Bowel Disease Questionnaire \[SIBDQ\], IBD Disability Index \[IBD-DI\], Treatment Burden Questionnaire, and Treatment Satisfaction Questionnaire for Medication) will be completed at baseline (following randomization) and up to 3 more additional times during the up to 2-year follow-up period.
Study design and administration
- Organization
- Mayo Clinic
- Organization class
- Other
- Organization study ID
- RCT01519
- Lead sponsor
- Mayo Clinic
- Sponsor class
- Other
- Enrollment type
- Estimated
- Allocation
- Randomized
- Intervention model
- Parallel
- Primary purpose
- Other
- Masking
- None
- Who is masked
- Not provided
- Standard age groups
- Adult, Older Adult
Study arms
Other
Switching Targeted Immunomodulators Treatment
Participants randomized to a strategy of switching TIM will be switched to one of the preferred agents recommended by clinical guidelines and covered by the participants' insurance formulary as part of routine care, and at the discretion of the site investigator and treating provider. No study-related medications will be provided. For participants randomized to switch to an alternative TIM, selection of alternative agent will be determined at the discretion of the local site physician in accordance with clinical guidelines on the management of moderate to severe ulcerative colitis, and management of moderate to severe CD from the AGA and ACG.9, 34, 35 These guidelines include recommendations on positioning of TIMs for first line use (TIM-naïve patients) and second-line use (in patients with prior exposure to TIMs).
Interventions: Other: Pragmatic
Other
Continuing Index Targeted Immunomodulators Treatment
Participants randomized to a strategy of continuing TIM will continue on their concomitant therapy.
Interventions: Other: Pragmatic
Interventions
Other
Pragmatic
Patients randomized to a strategy of switching TIM will be switched to one of the preferred agents recommended by clinical guidelines and covered by the patients' insurance formulary as part of routine care, and at the discretion of the site investigator and treating provider. No study-related medications will be provided. Patients (and their providers) in either treatment arm will be allowed to stop or start new TIMs and other IBD-directed therapies in case of symptomatic relapse or intolerance to therapies, at the discretion of the treating provider-patient team.
Eligibility
18 Years and older
All
Not accepted
Inclusion criteria (31)
- Participants must meet all of the following criteria for enrolment into the study.Registry-derived · unreviewed
- Male or nonpregnant, nonlactating females, ≥ 18 years of age.Registry-derived · unreviewed
- An established diagnosis of CD or UC for at least 6 months based on standard clinical criteria, confirmed by the treating provider.Registry-derived · unreviewed
- Current treatment with an approved TIM for treatment of IBD, including biologic agents (e.g., TNFα antagonists, ustekinumab, vedolizumab) and small molecule inhibitors (e.g., Janus kinase inhibitors, ozanimod), including future TIMs that become commercially available during the conduct of the trial.Registry-derived · unreviewed
- Dose of TIM should be stable for 3 or more months prior to qualifying endoscopy/radiology. No treatment escalation of TIM or addition of IMM, corticosteroid, or mesalamines after the qualifying endoscopy/radiology procedure up to randomization is permitted. Dose de-escalation after qualifying procedure is permissible at the discretion of the treating provider.Registry-derived · unreviewed
- In corticosteroid-free symptomatic remission based on validated PROs (PRO2 score) and deemed to be experiencing no other IBD-related symptoms in the opinion of the treating provider. Includes patients who may be in medically induced remission (on index TIM); or surgically induced remission with post-op initiation of index TIM for prophylaxis and colonoscopy/imaging performed at least 3 months after initiation/optimization of TIM showing moderate-severe bowel inflammation. Validated PROs are defined as:Registry-derived · unreviewed
- CD: PRO2 (2-item patient reported outcome) mean daily score of abdominal pain score ≤1 and stool frequency score ≤ 3; orRegistry-derived · unreviewed
- UC: PRO2, with absence of rectal bleeding (rectal bleeding score = 0) and with stool frequency score ≤1.Registry-derived · unreviewed
- Evidence of moderate to severe bowel inflammation on local reading of colonoscopy, flexible sigmoidoscopy, balloon-assisted enteroscopy, capsule endoscopy or MR, CT enterography, or intestinal ultrasound, performed within 6 months prior to screening, defined at the investigator's discretion or as follows:Registry-derived · unreviewed
- CD: Colonoscopy showing moderately to severely active inflammation based on 1 of the following variables/scores:Registry-derived · unreviewed
- Simple Endoscopic Score for Crohn's Disease (SES-CD) score ≥7 or score ≥4 for those with isolated ileal disease, orRegistry-derived · unreviewed
- Presence of mucosal ulcers \>5 mm in size if SES-CD has not been recorded, orRegistry-derived · unreviewed
- Simplified Endoscopic Mucosal Assessment for Crohn's Disease (SEMA-CD) score ≥2, orRegistry-derived · unreviewed
- Rutgeerts score i2b or higher for patients in surgically induced remission with post-operative endoscopic recurrence \[Note, either SES-CD or Rutgeerts score can be used for participants with post-operative recurrence\]; orRegistry-derived · unreviewed
- CD: MRE or CTE showing moderately to severely active inflammation based on 1 of the following variables:Registry-derived · unreviewed
- Increased bowel wall thickness, orRegistry-derived · unreviewed
- Mural hyperenhancement, orRegistry-derived · unreviewed
- Peri-enteric fat stranding, orRegistry-derived · unreviewed
- Radiographic features of ulceration, orRegistry-derived · unreviewed
- Intramural T2 signal on fat suppressed images; orRegistry-derived · unreviewed
- CD: Capsule endoscopy showing moderately to severely active small bowel disease based on Lewis score \>790 (in case the disease is not accessible via endoscopy), or per local endoscopist if Lewis score is not reported; orRegistry-derived · unreviewed
- CD: Gastrointestinal ultrasound showing at least 1 of the following variables:Registry-derived · unreviewed
- Increased bowel wall thickness \>5 mm, orRegistry-derived · unreviewed
- Color doppler score \>5/cm2, orRegistry-derived · unreviewed
- Bowel stenosis, orRegistry-derived · unreviewed
- Bowel stratification, orRegistry-derived · unreviewed
- Fatty wrapping; orRegistry-derived · unreviewed
- UC: modified MES score of 2 to 3, or documentation of any endoscopic feature that would define an MES of 2 to 3 (e.g., friability, ulceration, spontaneous bleeding, complete loss of vascular pattern), if an MES has not been recorded.Registry-derived · unreviewed
- Eligible to receive at least 1 alternative TIM (excluding their index TIM) for the treatment of their disease per approved drug label, based on clinical and reimbursement guidelines.Registry-derived · unreviewed
- Able to participate fully in all aspects of this clinical trial.Registry-derived · unreviewed
- Informed consent must be obtained and documented.Registry-derived · unreviewed
Exclusion criteria (6)
- Participants who exhibit any of the following conditions are to be excluded from the study.Registry-derived · unreviewed
- Presence of ostomy or ileoanal pouches.Registry-derived · unreviewed
- Serious underlying disease other than UC or CD that in the opinion of the investigator may interfere with the participant's ability to participate fully in the study.Registry-derived · unreviewed
- History of alcohol or drug abuse or any other medical or health condition that in the opinion of the investigator may interfere with the participant's ability to comply with the study procedures.Registry-derived · unreviewed
- Prior enrolment in the current study.Registry-derived · unreviewed
- Mild endoscopic disease activity, where treating providers would not consider switching TIM.Registry-derived · unreviewed
This information can identify a possible match, conflict, or item needing confirmation. Only the study team can determine eligibility.
Study outcomes
Primary outcome
Time to Treatment Failure
Time frame: From randomization up to 104 weeks
Time to treatment failure, as a composite of: (1) moderate severe symptomatic relapse based on PRO2, with objective confirmation of inflammation within 2 months of event (FC \>250 mcg/g, or CRP \>5mg/L, or endoscopy showing moderate-severe inflammation, or MRE/CTE/IUS showing active inflammation) with need for escalation of therapy; (2) need for rescue therapy with corticosteroids for a documented symptomatic IBD flare; (3) IBD related hospitalization; (4) IBD-related surgery; (5) IBD-related structural complications (CD: symptomatic stricture, fistula or abscess; UC: symptomatic stricture); (6) treatment-emergent adverse event requiring drug discontinuation
Secondary outcome
Treatment failure as defined in the composite primary outcome
Time frame: Binary, up to 104 weeks
Treatment failure as defined in the composite primary outcome
Secondary outcome
Time to each individual component of the composite primary outcome
Time frame: From randomization up to 104 weeks
Time to each individual component of the composite primary outcome
Secondary outcome
Overall Quality of Life
Time frame: Continuous, up to 104 weeks or Early Discontinuation
A) Scores of the SIBDQ. B) Scores of the IBD-Control. C) Scores of the PROMIS 7 scale. D) Scores of the on IBD-DI.
Secondary outcome
Treatment Burden/Satisfaction
Time frame: Continuous, up to 104 weeks or Early Discontinuation
A) Scores of Treatment Burden Questionnaire, including medication, time and administrative, lifestyle change, social life and financial burden. B) Scores of Treatment Satisfaction Questionnaire for Medication, measuring treatment satisfaction across domains of effectiveness, side effects, convenience and global satisfaction. C) Scores of the CoPaQ, including out-of-pocket costs, for management of IBD, including treatment, monitoring, outpatient visits, and any unplanned healthcare utilization.
Secondary outcome
Overall Safety
Time frame: Continuous, up to 104 weeks or Early Discontinuation
A) Treatment-related serious adverse events (SAEs) or unexpected SAEs. B) Serious infections, defined as infections requiring hospitalization and/or intravenous antibiotics.
Recruiting locations in the United States
Mayo Clinic Arizona
RecruitingScottsdale, Arizona, 85259, United States
Siddharth Singh, MD480-301-8000
Siddharth Singh, MD
Hoag Hospital
RecruitingIrvine, California, 92618, United States
Caroline Hwang, MD
Caroline Hwang, MD
UC San Diego Health
RecruitingLa Jolla, California, 92037, United States
Brigid Boland, MD858-657-7000
Brigid Boland, MD
Cedars-Sinai
RecruitingLos Angeles, California, 90048, United States
Gil Melmed, MD310-423-4100
Gil Melmed, MD
Sutter Health
RecruitingPalo Alto, California, 94301, United States
Ryan McConnell, MD484-995-1640
Ryan McConnell, MD
University of Colorado
RecruitingAurora, Colorado, 80045, United States
Mark Gerich, MD303-724-7244
Mark Gerich, MD
Yale University
RecruitingNew Haven, Connecticut, 06510, United States
Jill Gaidos, MD203-785-4138
Jill Gaidos, MD
MedStar Georgetown University Hospital
RecruitingWashington D.C., District of Columbia, 20007, United States
Mark Mattar, MD202-444-4898
Mark Mattar, MD
Mayo Clinic Jacksonville
RecruitingJacksonville, Florida, 32224, United States
Jana Al Hashash, MD904-953-0131
Jana Al Hashash, MD
Advent Health
RecruitingOrlando, Florida, 32804, United States
Jennifer Seminerio-Diehl, MD407-303-9921
Jennifer Seminerio-Diehl, MD
University of Chicago Medicine
RecruitingChicago, Illinois, 60637, United States
David Rubin, MD773-702-2950
David Rubin, MD
Dartmouth Hitchcock
RecruitingLebanon, New Hampshire, 03756, United States
Corey Siegel, MD603-650-5261
Corey Siegel, MD
Saratoga Schenectady Gastroenterology Associates
RecruitingBurnt Hills, New York, 12027, United States
Mark Metwally, MD518-831-1500
Mark Metwally, MD
Cornell University
RecruitingNew York, New York, 10021, United States
Dana Lukin, MD212-746-5077
Dana Lukin, MD
NYU Langone Health
RecruitingNew York, New York, 10016, United States
David Hudesman, MD855-698-4232
David Hudesman, MD
Gastroenterology Associates
RecruitingProvidence, Rhode Island, 02904, United States
Samir Shah, MD401-274-4800
Samir Shah, MD
University of Texas Southwestern
RecruitingDallas, Texas, 75235, United States
David Fudman, MD214-645-6355
David Fudman, MD
Baylor College of Medicine
RecruitingHouston, Texas, 77030, United States
Jason Hou, MD713-798-8220
Jason Hou, MD
University of Utah Health
RecruitingSalt Lake City, Utah, 84132, United States
Ann Flynn, MD801-587-7678
Ann Flynn, MD
Central study contacts
Registry dates
- First posted
- Feb 8, 2022
- Primary completion
- Aug 1, 2028
- Overall completion
- Feb 1, 2029
Trial information comes from ClinicalTrials.gov and may change. Confirm current status, eligibility, and site details with the study team. Aidy does not provide medical advice or determine eligibility.