Ulcer Healing Analysis for Inflammatory Bowel Disease

Overseen by Terrence Barrett, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

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

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial involves taking small pieces of tissue from the colon to study how ulcers heal. It includes patients with inflammatory bowel disease, arthritis, and healthy individuals to compare healing processes. Researchers will examine how genes work and how cells produce energy to understand healing.

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 data supports the effectiveness of the treatment Serial Biopsy, Entyvio, Entyvio Pen for healing ulcers in inflammatory bowel disease?

Research suggests that achieving mucosal healing (healing of the gut lining) in inflammatory bowel disease can lead to better patient outcomes, such as fewer hospital visits and surgeries. Although specific data on Entyvio is not provided, the general evidence indicates that treatments promoting mucosal healing are beneficial. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

The safety profile of biologic drugs, including those used for ulcerative colitis like vedolizumab (Entyvio), has been studied, showing they are generally safe for humans, though they may have some side effects. ^{6 7 8 9 10}

How does the drug Entyvio differ from other treatments for inflammatory bowel disease?

Entyvio (also known as vedolizumab) is unique because it specifically targets the gut by blocking a protein that causes inflammation, which may lead to better mucosal healing (repair of the gut lining) compared to other treatments that affect the entire immune system. This targeted approach can potentially result in fewer side effects and improved outcomes for patients with inflammatory bowel disease. ^{2 3 10 11 12}

Research Team

Terrence Barrett, MD

Principal Investigator

University of Kentucky

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Serial Biopsy (Procedure)

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.

Participant Groups

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).

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+

Dr. Griffin P. Rodgers

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

Chief Executive Officer since 2007

MD, M.A.C.P.

Dr. Griffin P. Rodgers

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

Chief Medical Officer since 2007

MD, M.A.C.P.

Findings from Research

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 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]

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]

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]

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]

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]

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 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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Fecal Calprotectin Predicts Relapse and Histological Mucosal Healing in Ulcerative Colitis. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Mucosal healing as a treatment for IBD? [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Predictors of tissue healing in ulcerative colitis patients treated with anti-TNF. [2017]

4. England 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? [2015]

5. United States pubmed.ncbi.nlm.nih.gov

Mucosal healing in inflammatory bowel disease. [2022]

6. England 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. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

Preliminary observations of oral nicotine therapy for inflammatory bowel disease: an open-label phase I-II study of tolerance. [2019]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Mucosal Healing in Ulcerative Colitis: A Comprehensive Review. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Mucosal healing in inflammatory bowel disease: treatment efficacy and predictive factors. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Combined use of CDAI and blood indices for assessing endoscopic activity in ileocolic Crohn's disease. [2023]

12. England 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. [2022]