Neuropathological Changes of the Intestinal Wall in Patients With Bowel Evacuation Disorders

NCT ID: NCT05016700

Last Updated: 2025-03-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

500 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-03-20

Study Completion Date

2033-12-31

Brief Summary

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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

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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.

Conditions

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Defecation Disorder Neuropathology Autoimmune Diseases

Study Design

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Observational Model Type

COHORT

Study Time Perspective

RETROSPECTIVE

Interventions

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blood sample

we want to identify a diagnostic option to identify patients, who have a neuropathological distraction of their ganglia cells in the bowel

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Cologne

OTHER

Sponsor Role collaborator

Evangelisches Klinikum Köln Weyertal gGmbH

OTHER

Sponsor Role lead

Responsible Party

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Claudia Rudroff

Head of the Department of Visceral Surgery and Functional Surgery of the lower GI Tract

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Claudia Rudroff, MD

Role: PRINCIPAL_INVESTIGATOR

Claudia Rudroff, MD PhD

Locations

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Evangelisches Klinikum Koeln Weyertal

Cologne, North Rhine-Westphalia, Germany

Site Status RECRUITING

Countries

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Germany

Central Contacts

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Claudia L Rudroff, MD

Role: CONTACT

+49221479 ext. 5110

Joshy Madukkakuzhy

Role: CONTACT

+49221479 ext. 5121

Facility Contacts

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Claudia L Rudroff, PhD MD

Role: primary

+49-221-479 ext. 5110

Joshy Madukkakuzhy

Role: backup

+49-221-479 ext. 5121

References

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Han EC, Oh HK, Ha HK, Choe EK, Moon SH, Ryoo SB, Park KJ. Favorable surgical treatment outcomes for chronic constipation with features of colonic pseudo-obstruction. World J Gastroenterol. 2012 Aug 28;18(32):4441-6. doi: 10.3748/wjg.v18.i32.4441.

Reference Type BACKGROUND
PMID: 22969211 (View on PubMed)

Bassotti G, Villanacci V, Nascimbeni R, Asteria CR, Fisogni S, Nesi G, Legrenzi L, Mariano M, Tonelli F, Morelli A, Salerni B. Colonic neuropathological aspects in patients with intractable constipation due to obstructed defecation. Mod Pathol. 2007 Mar;20(3):367-74. doi: 10.1038/modpathol.3800748. Epub 2007 Feb 2.

Reference Type BACKGROUND
PMID: 17277762 (View on PubMed)

Bassotti G, Villanacci V, Cathomas G, Maurer CA, Fisogni S, Cadei M, Baron L, Morelli A, Valloncini E, Salerni B. Enteric neuropathology of the terminal ileum in patients with intractable slow-transit constipation. Hum Pathol. 2006 Oct;37(10):1252-8. doi: 10.1016/j.humpath.2006.04.027. Epub 2006 Jul 20.

Reference Type BACKGROUND
PMID: 16949932 (View on PubMed)

Bassotti G, Villanacci V, Maurer CA, Fisogni S, Di Fabio F, Cadei M, Morelli A, Panagiotis T, Cathomas G, Salerni B. The role of glial cells and apoptosis of enteric neurones in the neuropathology of intractable slow transit constipation. Gut. 2006 Jan;55(1):41-6. doi: 10.1136/gut.2005.073197. Epub 2005 Jul 24.

Reference Type BACKGROUND
PMID: 16041063 (View on PubMed)

Wedel T, Roblick UJ, Ott V, Eggers R, Schiedeck TH, Krammer HJ, Bruch HP. Oligoneuronal hypoganglionosis in patients with idiopathic slow-transit constipation. Dis Colon Rectum. 2002 Jan;45(1):54-62. doi: 10.1007/s10350-004-6114-3.

Reference Type BACKGROUND
PMID: 11786765 (View on PubMed)

Valli PV, Pohl D, Fried M, Caduff R, Bauerfeind P. Diagnostic use of endoscopic full-thickness wall resection (eFTR)-a novel minimally invasive technique for colonic tissue sampling in patients with severe gastrointestinal motility disorders. Neurogastroenterol Motil. 2018 Jan;30(1). doi: 10.1111/nmo.13153. Epub 2017 Jul 6.

Reference Type BACKGROUND
PMID: 28681569 (View on PubMed)

Do MY, Myung SJ, Park HJ, Chung JW, Kim IW, Lee SM, Yu CS, Lee HK, Lee JK, Park YS, Jang SJ, Kim HJ, Ye BD, Byeon JS, Yang SK, Kim JH. Novel classification and pathogenetic analysis of hypoganglionosis and adult-onset Hirschsprung's disease. Dig Dis Sci. 2011 Jun;56(6):1818-27. doi: 10.1007/s10620-010-1522-9. Epub 2011 Jan 11.

Reference Type BACKGROUND
PMID: 21222160 (View on PubMed)

Porter CK, Choi D, Cash B, Pimentel M, Murray J, May L, Riddle MS. Pathogen-specific risk of chronic gastrointestinal disorders following bacterial causes of foodborne illness. BMC Gastroenterol. 2013 Mar 8;13:46. doi: 10.1186/1471-230X-13-46.

Reference Type BACKGROUND
PMID: 23510245 (View on PubMed)

Mearin F, Perello A, Balboa A, Perona M, Sans M, Salas A, Angulo S, Lloreta J, Benasayag R, Garcia-Gonzalez MA, Perez-Oliveras M, Coderch J. Pathogenic mechanisms of postinfectious functional gastrointestinal disorders: results 3 years after gastroenteritis. Scand J Gastroenterol. 2009;44(10):1173-85. doi: 10.1080/00365520903171276.

Reference Type BACKGROUND
PMID: 19711225 (View on PubMed)

Sanchez-Ruiz M, Brunn A, Montesinos-Rongen M, Rudroff C, Hartmann M, Schluter D, Pfitzer G, Deckert M. Enteric Murine Ganglionitis Induced by Autoimmune CD8 T Cells Mimics Human Gastrointestinal Dysmotility. Am J Pathol. 2019 Mar;189(3):540-551. doi: 10.1016/j.ajpath.2018.11.016. Epub 2018 Dec 27.

Reference Type RESULT
PMID: 30593823 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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EVKKoeln

Identifier Type: -

Identifier Source: org_study_id

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