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

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

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

About this study

Although conservative treatment of Crohn's disease (CD) is constantly improving some patients still require surgery. Optimal perioperative management includes pharmacological modifications to reduce complications risk. Unfavorable effect of steroids and from recently also biologics on intraabdominal and wound septic complications is known, but until now azathioprine (AZA) is considered to be safe.

The aim of our study was to assess the impact of AZA on intestinal epithelial cells damage as well as restoration and regeneration in patients with active CD as a surrogate marker of healing. We assessed intestinal specimens taken from macroscopically healthy surgical margins of all consecutive CD patients operated due to active isolated ileocecal disease during the study period (2014-2016) in tertiary referral center. We immunohistochemically tested expression of Ki-67, caspase-3 and p-53 as a markers of cell proliferation, apoptosis and DNA damage respectively. Quantitative evaluation of cellular expression of determined proteins was assessed using a confocal microscope. We also performed immunofluorescent tests for cellular integrity using ZO-1 and E-cadherin proteins expression. Additionally we assessed 30 days clinical outcomes.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

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

Treatment and study plan

Primary outcomes

histopathological assessment of the azathioprine's impact on intestinal damage

Time frame: 30 days

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.

Sponsors and collaborators

Lead sponsor

Centre of Postgraduate Medical Education

Other

Registry information

Important dates

Study start: 2014
Primary completion: 2016
Study completion: 2019
First posted: Jul 13, 2022
Registry last updated: Jul 13, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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