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

Autoimmune Diseases Clinical Trial

— Constipation  

Official title:

Correlation of Clinical Symptoms With Neuromorphological Changes of the Colorectal Wall in Patients With a Bowel Evacuation Disorder

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05016700
• Other study ID #: EVKKoeln
• Status: Recruiting
• Start date: March 20, 2019
• Est. completion date: December 31, 2033

Study information

• Verified date: January 2024
• Source: Evangelisches Klinikum Köln Weyertal gGmbH
• Contact: Claudia L Rudroff, MD
• Phone: +49221479
• Email: claudia.rudroff[@]evk-koeln.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: December 31, 2033
• Est. primary completion date: December 31, 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Autoimmune Diseases
• Neuropathology

Intervention

Diagnostic Test:
• blood sample
we want to identify a diagnostic option to identify patients, who have a neuropathological distraction of their ganglia cells in the bowel

Locations

Country	Name	City	State
Germany	Evangelisches Klinikum Koeln Weyertal	Cologne	Northrhine Westphalia

Sponsors (2)

Lead Sponsor	Collaborator
Evangelisches Klinikum Köln Weyertal gGmbH	University of Cologne

Country where clinical trial is conducted

Germany, 

References & Publications (10)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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: 10.1 — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Correlation of psychic health and neuropathological changes of the intestinal wall in patients with defecation disorder	Changes in QoL and relief from depressive symptoms after surgery measured by clinical psysic health questionnaire (PHQ 9) ; minimum 0 to maximum 27 points; higher scores mean worse outcome	10 years
Secondary	Correlation of anxiety scoring and neuropathological changes of the intestinal wall in patients with defecation disorder	Changes in anxiety symptoms after surgery measured by clinical general anxiety score (GAD 7); minimum 0 to maximum 21 points; higher scores mean worse outcome	10 years
Secondary	Association of pathological findings for autoimmune activation with duration of symptoms according to medical history	Onset of symptoms in correlation to severity and picture of pathological findings in months	questionaire at inclusion to study
Secondary	Association of pathological findings for autoimmune reaction with an initiating event according to the medical questionaire	Identification of an initiating event to the occurrence of the symptoms	questionaire at inclusion to study
Secondary	Correlation of abdominal discomforting symptoms and neuropathological changes of the intestinal wall in patients with bowel evacuation disorder	Clinical outcome measure rectal toxicity score (minimum 0 to maximum 32 points; higher scores mean worse outcome)	10 years
Secondary	Correlation of neuropathological changes of the intestinal wall in patients with bowel evacuation disorder and clinical defecation insufficiency (incontinence)	Clinical outcome measure by score: Wexner (name of initiator) incontinence score (minimum 0 to maximum 20 points; higher scores mean worse outcome)	10 years