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

NCT05016700 | Recruiting

• 1 other identifier: EVKKoeln
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

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.

Conditions

Defecation Disorder; Neuropathology; Autoimmune Diseases

Keywords

Neuropathology; Defecation disorder; Autoimmune disease; Hypoganglionosis; Autoimmune ganglionitis; Neurological bowel disorder; Colon surgery

Outcome Measures

Primary Outcomes (1)

• Neuropathological changes of the intestinal wall in patients with bowel evacuation disorder in correlation to clinical defecation score

  Clinical outcome measure by score: Altomare Score (name of initiator) score (minimum 0 to maximum 30 points; higher values mean worse outcome)

  10 years

Secondary Outcomes (6)

• Correlation of psychic health and neuropathological changes of the intestinal wall in patients with defecation disorder

  10 years

• Correlation of anxiety scoring and neuropathological changes of the intestinal wall in patients with defecation disorder

  10 years

• Association of pathological findings for autoimmune activation with duration of symptoms according to medical history

  questionaire at inclusion to study

• Association of pathological findings for autoimmune reaction with an initiating event according to the medical questionaire

  questionaire at inclusion to study

• Correlation of abdominal discomforting symptoms and neuropathological changes of the intestinal wall in patients with bowel evacuation disorder

  10 years

Interventions

blood sample DIAGNOSTIC_TEST

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

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Evangelisches Klinikum Köln Weyertal gGmbH: lead
• University of Cologne: collaborator

Study Sites (1)

Evangelisches Klinikum Koeln Weyertal

Cologne, North Rhine-Westphalia, 50931, Germany

RECRUITING

Related Publications (10)

• 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.

  PMID: 22969211 BACKGROUND

• 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.

  PMID: 17277762 BACKGROUND

• 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.

  PMID: 16949932 BACKGROUND

• 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.

  PMID: 16041063 BACKGROUND

• 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.

  PMID: 11786765 BACKGROUND

• 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.

  PMID: 28681569 BACKGROUND

• 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.

  PMID: 21222160 BACKGROUND

• 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.

  PMID: 23510245 BACKGROUND

• 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.

  PMID: 19711225 BACKGROUND

• 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.

  PMID: 30593823 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples (EDTA) to investigate immunological activation for the individual patient

MeSH Terms

Conditions

Autoimmune Diseases

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Claudia Rudroff, MD

  Claudia Rudroff, MD PhD

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Claudia L Rudroff, MD

CONTACT

+49221479; claudia@rudroff.com

Joshy Madukkakuzhy

CONTACT

+49221479; joshy.madukkakuzhy@evk-koeln.de

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of the Department of Visceral Surgery and Functional Surgery of the lower GI Tract

Study Record Dates

• First Submitted: July 24, 2021
• First Posted: August 23, 2021
• Study Start: March 20, 2019
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2033
• Last Updated: March 10, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: now
• Access Criteria: open

Locations

DE (1)