Inflammatory Bowel DiseasesNCT05456776
Azathioprine Linked With Impaired Intestinal Epithelial Postoperative Regeneration in Crohn's Disease
An observational study of Inflammatory Bowel Diseases, run by Centre of Postgraduate Medical Education.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Inflammatory Bowel Diseases
- How many people
- 35 participants
- Where
- No sites listed yet
- Study dates
- Apr 2014to Oct 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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).
Who may be able to join
- 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
Who cannot join
- 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
About this study
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
Read the detailed description
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.
- Conditions
- Inflammatory Bowel Diseases
- Keywords
- azathioprine, immunomodulators, epithelial repair, restitution, regeneration, cellular damage, Crohn's disease, apoptosis, p53, caspase-3, Ki67
- Medical subject headings
- Inflammatory Bowel Diseases, Crohn Disease, Spinocerebellar Ataxias
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2022
- Study startApr 2014
- Primary completionDec 2016
- Study completionOct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Inflammatory Bowel DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre of Postgraduate Medical Education
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05456776
- Sponsor's protocol ID
- nr 2803/2012
- Status last verified
- Jul 2022
- First submitted
- 6 Jul 2022
- Last updated
- 13 Jul 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Azathioprine Linked With Impaired Intestinal Epithelial Postoperative Regeneration in Crohn's Disease
- ClinicalTrials.gov ID
- NCT05456776
- Acronym / sponsor ID
- nr 2803/2012
- Conditions
- Inflammatory Bowel Diseases
- Keywords
- azathioprine, immunomodulators, epithelial repair, restitution, regeneration, cellular damage, Crohn's disease, apoptosis, p53, caspase-3, Ki67
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Centre of Postgraduate Medical EducationUniversity, hospital or other
- Study start
- Apr 2014 (actual)
- Primary completion
- Dec 2016 (actual)
- Study completion
- Oct 2019 (actual)
- First posted
- 13 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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).
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
An observational study of Inflammatory Bowel Diseases, run by Centre of Postgraduate Medical Education.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
histopathological assessment of the azathioprine's impact on intestinal damage (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2022.