Ulcer Healing Analysis for Inflammatory Bowel Disease

Overseen By Neeraj Kapur, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Terrence A Barrett

Must be taking: Anti-TNF therapy

Must not be taking: Anticoagulants, Anti-platelets, Steroids, Metformin

Disqualifiers: Pregnant, HIV positive, Stroke, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 5 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how colonic ulcers heal in individuals with inflammatory bowel disease (IBD) compared to healthy individuals and those with rheumatoid or psoriatic arthritis. Researchers will analyze small tissue samples (biopsies) to understand gene and cell energy patterns during healing. Individuals with ulcerative colitis or Crohn's disease, especially those who have tried or are new to biologic treatments like Entyvio (also known as Entyvio Pen), or those with arthritis on anti-TNF therapy, might be suitable candidates. As an unphased trial, this study provides a unique opportunity to contribute to scientific understanding and potentially improve future treatments for IBD and arthritis.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on anticoagulants, anti-platelet medications (except low-dose aspirin), steroids, or metformin.

What prior data suggests that this biopsy method is safe?

Research shows that the main procedure in this study, serial biopsy, is generally safe. A biopsy involves taking a small piece of tissue from the body to check for disease. It is a common procedure, and most people handle it well. Serious side effects are rare, but some discomfort or minor bleeding may occur, which are usually not severe.

In this study, participants with inflammatory bowel disease (IBD), rheumatoid arthritis, psoriatic arthritis, and healthy volunteers will undergo biopsies. The focus is on the biopsy process itself, not on testing a new drug or treatment. No new medication is being tested for safety, only the biopsy procedure.

In summary, serial biopsy is a routine procedure and is considered safe, with only minor side effects reported in most cases. Prospective participants should discuss any concerns with the study team. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it focuses on using serial biopsy to better understand ulcer healing in conditions like ulcerative colitis and Crohn's disease. Unlike traditional treatments that primarily rely on medication to manage symptoms, this technique aims to provide detailed insights into the healing process at a cellular level. By closely examining tissue samples over time, researchers hope to identify new therapeutic targets and improve personalized treatment plans, potentially leading to more effective and tailored care for patients with inflammatory bowel disease.

What evidence suggests that this trial's treatments could be effective for ulcer healing in inflammatory bowel disease?

Research has shown that treatments like Entyvio can benefit people with ulcerative colitis and Crohn's disease, both types of inflammatory bowel disease (IBD). In some studies, patients taking Entyvio experienced significant symptom improvement by Week 52, with some noticing benefits as early as Week 6, sometimes without needing steroids. These findings suggest that targeting specific parts of the immune system can aid in gut healing for IBD. Such treatments aim to reduce inflammation, which is crucial for managing these conditions. Participants in this trial will belong to different groups, including those with IBD, those with rheumatoid or psoriatic arthritis, and healthy controls, to analyze ulcer healing across these conditions. ^{1 4 5 6 7}

Who Is on the Research Team?

Terrence Barrett, MD

Principal Investigator

University of Kentucky

Are You a Good Fit for This Trial?

This trial is for people with ulcerative colitis or Crohn's disease who haven't responded to or haven't tried biologic treatments, and those with rheumatoid or psoriatic arthritis on anti-TNF therapy. Healthy individuals with normal colonic mucosa can also participate.

Inclusion Criteria

I have been diagnosed with ulcerative colitis or Crohn's disease.

I have been diagnosed with rheumatoid or psoriatic arthritis.

I have either not responded to biologic treatment or have never received it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Biopsy

Biopsies are collected at baseline during standard of care endoscopy

1 day

1 visit (in-person)

Treatment

Participants receive anti-TNF therapy as part of their standard care

5 weeks

Follow-up Biopsy

Biopsies are collected at a follow-up research endoscopy to assess healing

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in gene expression and ulcer healing

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Serial Biopsy

Trial Overview The study involves taking small tissue samples (biopsies) from the colon at two different times to compare healing processes in patients with IBD against those in healthy controls and arthritis patients.

How Is the Trial Designed?

Group I: Rheumatoid/Psoriatic Arthritis Experimental Treatment 1 Intervention

Participants in this group will have been diagnosed with rheumatoid (RA) or psoriatic arthritis (PsA) and will be receiving anti-TNF antibody therapy at the time of enrollment.

Group II: Inflammatory Bowel Disease Experimental Treatment 1 Intervention

Participants in this group will have been diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) and have either failed treatment with biologics or be naive to biologic therapy.

Group III: Healthy Controls Experimental Treatment 1 Intervention

Participants in this group will be healthy (not diagnosed with inflammatory bowel disease).

Serial Biopsy is already approved in United States, European Union for the following indications:

Approved in United States as Entyvio for:

• Moderate to severe ulcerative colitis
• Crohn's disease

Approved in European Union as Entyvio for:

• Moderate to severe ulcerative colitis
• Crohn's disease

Who Is Running the Clinical Trial?

Terrence A Barrett

Lead Sponsor

Trials

1

Recruited

60+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

Mucosal healing is becoming a key goal in treating inflammatory bowel disease, as it may lead to better patient outcomes, including sustained remission and fewer hospitalizations.

There is currently no standardized definition of mucosal healing, making it challenging to evaluate the effectiveness of different treatments and their long-term impact on disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mucosal healing as a treatment for IBD? Papi, C., Aratari, A.[2022]

In a study of 67 ulcerative colitis patients, those treated with a combination of anti-TNFα agents and azathioprine showed a higher rate of mucosal healing (43.3%) compared to those on anti-TNFα monotherapy, indicating that combination therapy may be more effective.

Mucosal healing was linked to specific pre-treatment levels of T helper cell transcription factors, with lower levels of Th1-Tbet and higher levels of Th17-Rorc associated with better outcomes, suggesting that these factors could help predict treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of tissue healing in ulcerative colitis patients treated with anti-TNF. Viazis, N., Giakoumis, M., Bamias, G., et al.[2017]

In a study of adults with moderate to severe Crohn's disease receiving adalimumab, mucosal healing was significantly more pronounced in the rectum, sigmoid/left colon, and transverse colon compared to the right colon and ileum after 52 weeks of treatment.

The analysis revealed that at Week 52, 28.3% of patients showed healing in the colon compared to 21.2% in the ileum, indicating that different segments of the intestine respond differently to adalimumab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterisation of Mucosal Healing with Adalimumab Treatment in Patients with Moderately to Severely Active Crohn's Disease: Results from the EXTEND Trial. Reinisch, W., Colombel, JF., D'Haens, G., et al.[2022]

In a study of 26 patients with ulcerative colitis and Crohn's colitis, oral nicotine therapy was generally well-tolerated, with 29 out of 31 patients able to tolerate at least 6 mg daily, indicating its potential as a safe treatment option.

While 6 out of 13 patients with active disease became asymptomatic after treatment, some patients experienced adverse events, leading to 7 discontinuations, highlighting the need for careful monitoring of tolerance during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary observations of oral nicotine therapy for inflammatory bowel disease: an open-label phase I-II study of tolerance. Ingram, JR., Rhodes, J., Evans, BK., et al.[2019]

Mucosal healing (MH) is essential in managing ulcerative colitis (UC) as it leads to lower rates of clinical relapse, hospitalization, and colorectal cancer, highlighting its importance in improving patient outcomes.

Several approved drugs, including anti-TNFα drugs and vedolizumab, have proven efficacy in achieving MH, emphasizing the need for a strict definition of complete MH as a treatment goal for UC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mucosal Healing in Ulcerative Colitis: A Comprehensive Review. Boal Carvalho, P., Cotter, J.[2022]

Mucosal healing is increasingly recognized as an important goal in treating inflammatory bowel disease (IBD), as it is linked to better clinical outcomes for patients with Crohn's disease and ulcerative colitis.

Despite its potential benefits, the use of mucosal healing as a standard treatment endpoint is still developing, facing challenges that hinder its routine application in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mucosal healing in inflammatory bowel disease. Osterman, MT.[2022]

Mucosal healing is a key therapeutic goal in inflammatory bowel disease, as it can improve patient outcomes and potentially change the disease's progression.

Anti-TNFα therapies have been shown to induce rapid and sustained mucosal healing in a significant number of patients with Crohn's disease and ulcerative colitis, although predicting which patients will achieve this healing remains challenging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mucosal healing in inflammatory bowel disease: treatment efficacy and predictive factors. Papi, C., Fascì-Spurio, F., Rogai, F., et al.[2022]

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]

A comprehensive index combining the Crohn's Disease Activity Index (CDAI), C-reactive protein (CRP), and platelet-to-lymphocyte percentage ratio (PLpR) significantly improves the prediction of endoscopic activity in patients with ileocolic Crohn's disease, outperforming CDAI alone.

In a study of 300 patients, the new index demonstrated strong predictive performance with an area under the curve (AUC) of 0.849, indicating it is a reliable tool for monitoring disease activity and potential flares.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined use of CDAI and blood indices for assessing endoscopic activity in ileocolic Crohn's disease. Hu, X., Li, J., Sun, Y., et al.[2023]

Fecal calprotectin (FC) levels above 321 mg/kg can predict disease relapse in ulcerative colitis patients at 6 and 12 months, suggesting it is a reliable noninvasive biomarker for monitoring disease progression.

Regular measurement of FC may reduce the need for invasive procedures like endoscopy while improving patient prognosis by identifying those at higher risk for relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Calprotectin Predicts Relapse and Histological Mucosal Healing in Ulcerative Colitis. Theede, K., Holck, S., Ibsen, P., et al.[2022]

Mucosal healing is a key goal in managing inflammatory bowel diseases, as it is linked to better disease outcomes, but defining what constitutes complete or partial healing remains unclear.

Current assessment methods for mucosal healing, such as endoscopy and imaging, are often invasive and costly, making them less suitable for regular monitoring in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical aspects of mucosal healing in inflammatory bowel diseases: what is it and what is the real value for the everyday practice? Miheller, P., Mandel, MD., Mullner, K., et al.[2015]

In a study of 773 ulcerative colitis patients, those treated with biologics or Janus kinase inhibitors (BIO/JAKi) had lower remission rates and more severe disease compared to those on 5-aminosalicylic acids (5-ASAs), indicating a higher disease burden.

Despite having more treatment options, BIO/JAKi patients reported worse patient-reported outcomes, including higher absenteeism and activity impairment, suggesting ongoing challenges in managing ulcerative colitis effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disease Burden and Patient-Reported Outcomes Among Ulcerative Colitis Patients According to Therapy at Enrollment Into CorEvitas' Inflammatory Bowel Disease Registry. Cross, RK., Naegeli, AN., Harrison, RW., et al.[2023]

Citations

1. entyviohcp.com entyviohcp.com/ulcerative-colitis-efficacy

Demonstrated efficacy in ulcerative colitis *Many patients taking ENTYVIO IV achieved remission at Week 52 vs placebo, some without steroids. Some achieved remission at Week 6.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9322578/

Real‐world data on switching from intravenous to ... Long‐term effectiveness of vedolizumab in inflammatory bowel disease: a national study based on the Swedish National Quality Registry for inflammatory bowel ...

3. ema.europa.eu ema.europa.eu/en/documents/product-information/entyvio-epar-product-information_en.pdf

entyvio-epar-product-information_en.pdf - EMA The risk of malignancy is increased in patients with ulcerative colitis and Crohn's disease. Immunomodulatory medicinal products may increase the risk of ...

4. clinicaltrialsarena.com clinicaltrialsarena.com/marketdata/entyvio-treatment-uc-cd/

Entyvio for the Treatment of Ulcerative Colitis and Crohn's ... Results demonstrated that patients treated with Entyvio achieved and maintained greater clinical response and a greater clinical remission, as ...

5. mdpi.com mdpi.com/2077-0383/12/24/7657

Switching Vedolizumab from IV to SC Injection in ... Results: Eighty-two patients were included in the study. Of them, 35 patients had active disease (35/82 = 43%) at the time of the switch and 47 ...

6. entyviohcp.com entyviohcp.com/

ENTYVIO® (vedolizumab) - Official HCP Website Many patients taking ENTYVIO IV achieved remission at Week 52 vs placebo, some without steroids. Some achieved remission at Week 6. Clinical remission was ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2025/761359Orig1s000MultidisciplineR.pdf

761359Orig1s000 - accessdata.fda.gov The current BLA 761359 provides for Entyvio (vedolizumab) injection and Entyvio. Pen (vedolizumab) injection for long-term maintenance therapy ...