Clinical trial NCT05016700: Neuropathological Changes of the Intestinal Wall in Patients With Bowel Evacuation Disorders
Official title: Correlation of Clinical Symptoms With Neuromorphological Changes of the Colorectal Wall in Patients With a Bowel Evacuation Disorder
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Defecation Disorder
Neuropathology
Autoimmune Diseases
Keywords: Neuropathology
Defecation disorder
Autoimmune disease
Hypoganglionosis
Autoimmune ganglionitis
Neurological bowel disorder
Colon surgery
Lead sponsor: Evangelisches Klinikum Köln Weyertal gGmbH
Sponsor class: OTHER
Collaborators: name: University of Cologne
First posted: 2021-08-23
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with severe defecation disorders, both in terms of colonic transit disorder and obstructive defecation disorder, and combinations of both, who have been managed conservatively and require a full-wall bowel biopsy or bowel resection for medical indication.

Brief summary: Constipation and defecation disorders affect about 15% of the European population and of those up to 30% of the patients over 65 years of age. For those affected, this is associated with major restrictions in quality of life and high health care costs .

The underlying causes of constipation and defecation are complex and only partially understood.

Intestinal (full wall) resections taken in clinical practice from these patients when conservative therapy has been exhausted show rarefaction of ganglion cell nests in the myenteric plexus and submucosal plexus as well as changes in cholinergic innervation.

Initial histopathological investigations suggest an inflammatory genesis of this rarefaction of ganglion cell nests, which will be further characterised/investigated in the context of this study on the basis of further histopathological and serological investigations. This may lead to novel therapeutic approaches that can causally treat the symptoms of those affected.

Detailed description: Intestinal transit disorders (constipation/obstipation) and/or defecation disorders (expulsion disorders) are widespread symptoms in our culture, which, depending on their severity, can become a disease. Epidemiological studies show that up to 30% of the population over the age of 65 is affected. The suffering of those affected is usually very high.

The patients are usually treated conservatively at first. The focus is on lifestyle changes, dietary adjustments and medication to support bowel movements. If the symptoms persist despite consistent conservative therapy, additional diagnostics such as laboratory tests, sonography and colonoscopy are performed.

Further diagnostic steps include anal manometry, defecography and colon transit time.

From 2015 onwards, the systematic neuropathological examination of whole-wall samples was performed on the bowel specimen of patients who were surgically treated for defecation disorders. In addition, in individual cases in which no bowel resection was indicated, rectal full-wall samples were taken to confirm the diagnosis and indication for sacral nerve stimulation (SNS) and examined neuropathologically in the same way. The intestinal wall was examined for ganglion cell nests in the myenteric plexus and the submucosal plexus in order to identify the pathophysiological cause of the transport disorder.

The analysis showed rarefaction of the ganglion cell nests in the myenteric plexus and the submucosal plexus, as well as both a change in the cholinergic innervation and changes that suggest an autoimmune initiated process.

Increasing evidence links gastroenteritic germs with chronic intestinal motility disorders, so that a Campylobacter or Yersinia infection could well be the trigger for the observed neuropathological changes.

The aim of the study is to analyse the pathomechanism of chronic intestinal emptying disorders. Neuropathological findings on the plexus of the intestinal wall specimen are correlated to clinical findings measured by clinical scores in order to identify a diagnostic pattern.

Eligibility criteria: Inclusion Criteria:

* obstructive defecation disorder scheduled for surgery
* must be able to undergo surgery
* \> 18 years of age
* informed consent

Exclusion Criteria:

* no defecation disorder
* no surgery needed
* unable to undergo surgery
* ≤ 18 years
* no consent

Primary outcomes:
measure: Neuropathological changes of the intestinal wall in patients with bowel evacuation disorder in correlation to clinical defecation score
timeFrame: 10 years
Secondary outcomes:
measure: Correlation of psychic health and neuropathological changes of the intestinal wall in patients with defecation disorder
timeFrame: 10 years
measure: Correlation of anxiety scoring and neuropathological changes of the intestinal wall in patients with defecation disorder
timeFrame: 10 years
measure: Association of pathological findings for autoimmune activation with duration of symptoms according to medical history
timeFrame: questionaire at inclusion to study
measure: Association of pathological findings for autoimmune reaction with an initiating event according to the medical questionaire
timeFrame: questionaire at inclusion to study
measure: Correlation of abdominal discomforting symptoms and neuropathological changes of the intestinal wall in patients with bowel evacuation disorder
timeFrame: 10 years
measure: Correlation of neuropathological changes of the intestinal wall in patients with bowel evacuation disorder and clinical defecation insufficiency (incontinence)
timeFrame: 10 years
Other outcomes:
Locations:
city: Cologne
country: Germany
facility: Evangelisches Klinikum Koeln Weyertal
state: Northrhine Westphalia
Study officials:
affiliation: Claudia Rudroff, MD PhD
name: Claudia Rudroff, MD
role: PRINCIPAL_INVESTIGATOR
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