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| Name | Class |
|---|---|
| University of Cologne | OTHER |
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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.
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.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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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.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Claudia L Rudroff, MD | Contact | +49221479 | 5110 | claudia@rudroff.com |
| Joshy Madukkakuzhy | Contact | +49221479 | 5121 | joshy.madukkakuzhy@evk-koeln.de |
| Name | Affiliation | Role |
|---|---|---|
| Claudia Rudroff, MD | Claudia Rudroff, MD PhD | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Evangelisches Klinikum Koeln Weyertal | Recruiting | Cologne | North Rhine-Westphalia | 50931 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22969211 | Background | 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. | |
| 17277762 | 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. |
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After publication of data all data will be uploaded to clinical trials
now
open
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 18, 2018 | Aug 13, 2021 | Prot_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Feb 27, 2019 | Aug 13, 2021 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D001327 | Autoimmune Diseases |
| ID | Term |
|---|---|
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
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Blood samples (EDTA) to investigate immunological activation for the individual patient
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 16949932 | 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. |
| 16041063 | 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. |
| 11786765 | 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. |
| 28681569 | 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. |
| 21222160 | 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. |
| 23510245 | 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. |
| 19711225 | 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. |
| 30593823 | Result | 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. |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |