Azathioprine Linked With Impaired Intestinal Epithelial Postoperative Regeneration in Crohn's Disease

NCT05456776 | Completed

• 1 other identifier: nr 2803/2012
• Study Type: observational
• Target: 35
• Locations: 0 countries
• Sites: N/A

Brief Summary

What is known?

• the impact of AZA, immunomodulatory drug widely used in active CD, on the intestinal wall differs from those of steroids, what is reflected in the significant difference in the postoperative anastomotic leaks rate
• AZA inhibits intestinal epithelial cell growth by inducing the apoptosis and inhibiting proliferation of intestinal epithelial cells in in vitro studies What is new?
• The effect of AZA on cellular damage was assessed in humans' study
• AZA increases cell apoptosis in the intestinal epithelium of active CD patients, much stronger than steroids
• AZA actively promotes the DNA damage repair in the intestinal epithelium; the steroid effect, even when combined with AZA, is not so pronounced
• The intensity of proliferative processes, in contrast to steroids, is significantly inhibited in response to AZA
• The disintegration of the mucosa layer in response to AZA is observed
• The difference in the mechanisms of action of AZA and steroids on the intestinal mucosa may be directly related to the reported difference in the risk of septic postoperative complications, but this requires further research

Conditions

Inflammatory Bowel Diseases

Keywords

azathioprine, immunomodulators; epithelial repair; restitution, regeneration; cellular damage; Crohn's disease; apoptosis, p53, caspase-3, Ki67

Outcome Measures

Primary Outcomes (1)

• histopathological assessment of the azathioprine's impact on intestinal damage

  Comparison of the impact of immunomodulatory drugs on regeneration and restoration of small and large bowel's epithelial cells not affected by Crohn's disease. It was immunohistochemical assessment of expression of caspase-3, p-53 and Ki-67 as a markers of cell apoptosis, DNA damage and proliferation, respectively. But all of those stainings were then assessed by histopathologist in white light microscope. Quantitative evaluation (counting in high power field) of cellular expression of determined proteins was assessed using a confocal microscope.

  30 days

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The eligible population were male and female patients diagnosed with histopathologically confirmed CD at least six months earlier, operated due to active disease characterised by clinical, endoscopical, and radiological findings. Qualification to surgery was performed by multidisciplinary team consisting of surgeon, gastroenterologist, endoscopist and radiologist and was based on those data. Only patients with isolated ileocecal involvement were included for further evaluation. For the purpose of the study, we divided our cohort into four groups accordingly to preoperative treatment: group N - patients treated with no immunomodulators, group S - patients on steroids, group A - patients on AZA, and group AS - on combination therapy (AZA + steroids).

You may qualify if:

• diagnosed with histopathologically confirmed CD at least six months earlier, operated due to active disease characterised by clinical, endoscopical, and radiological findings
• ileocecal involvement
• No other CD manifestations
• Signed informed consent

You may not qualify if:

• Previous bowel surgery for CD
• Presence of severe, progressive, uncontrolled cardiological, pulmonary, nephrology, contagious or psychiatric illness whose course could affect the patient's risk of perioperative complications
• Significant disease symptoms so far undiagnosed
• Present or suspected malignancy or previous oncological treatment in the last five years
• Cardiac stimulator or cardioverter-defibrillator
• Pregnancy
• Severe non-abdominal surgery or severe trauma in the last year

Sponsors & Collaborators

• Centre of Postgraduate Medical Education: lead

Biospecimen

Retention: SAMPLES WITHOUT DNA

Intestinal samples from macroscopically healthy margins of surgical specimens. Two, one-centimeter each, fragments of the small intestine were cut off from the proximal end of the specimen (S1, S2) and analogous two from the large intestine (L1, L2) of the distal end. Then, all samples were inherently prepared and transferred for immunofluorescence (S1, L1) and Western-blot (S2, L2) analysis, while the whole remaining specimen delivered for histopathological examination.

MeSH Terms

Conditions

Inflammatory Bowel Diseases; Crohn Disease; Spinocerebellar Ataxias

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Cerebellar Ataxia; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinocerebellar Degenerations; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Ataxia; Dyskinesias; Neurologic Manifestations; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2022
• First Posted: July 13, 2022
• Study Start: April 1, 2014
• Primary Completion: December 1, 2016
• Study Completion: October 1, 2019
• Last Updated: July 13, 2022

Record last verified: 2022-07