NCT03617640

Brief Summary

Hirschsprung's disease (HD) is diagnosed shortly after birth and is characterized by the presence of megacolon. HD is caused when ganglion cells of the enteric nervous system (ENS) in the wall of the large intestine do not develop before birth. This results in a lack of gastrointestinal motility and leads to stool obstruction. It is known that ablation of enteric nerves is associated with intestinal infection and inflammation. Indeed the most severe complication in HD is Hirschsprung's associated enterocolitis (HAEC), characterized by explosive diarrhea, abdominal distension, fever and impending septic shock. Bacteria overgrowth and changes in colonic mucosal immune cell populations during HAEC suggest a possible defect in mucosal immune homeostasis. Under steady state conditions, the mucosal immune system must be tightly controlled to avoid harmful reactions against commensal flora and food antigens, while allowing protective immune responses against invading pathogens. This balance between tolerance and defense is influenced by the mucosal microenvironment, which in turn determines the phenotype and stability of mucosal immune cell populations. The goal of this project is to understand if the enteric nervous system plays a role in regulating mucosal immunity and how this might contribute to the development of HAEC.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
103

participants targeted

Target at P50-P75 for all trials

Timeline
Completed

Started Feb 2015

Longer than P75 for all trials

Geographic Reach
2 countries

8 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 28, 2015

Completed
3.4 years until next milestone

First Submitted

Initial submission to the registry

July 24, 2018

Completed
13 days until next milestone

First Posted

Study publicly available on registry

August 6, 2018

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 28, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 28, 2022

Completed
Last Updated

November 4, 2022

Status Verified

November 1, 2022

Enrollment Period

7 years

First QC Date

July 24, 2018

Last Update Submit

November 3, 2022

Conditions

Hirschsprung's Disease Associated Enterocolitis

Keywords

enteric neuropathiesImmune cellsNervous cellsMicrobiom

Outcome Measures

Primary Outcomes (3)

  • Phenotypic analysis of immune and nervous cell populations

    Determining cell frequencies and subtypes using fluorescence-activated cell sorting (FACS) and FlowJo software

    5 years

  • Expression profil

    RNA expression profile of whole colon tissue and single cell populations

    5 years

  • Histological analysis

    Microscopic analysis of colonic tissue using immunofluorescence and immunohistochemistry

    5 years

Secondary Outcomes (2)

  • Microbial metagenomics sequencing

    5 years

  • Identifying genetic defect

    5 years

Study Arms (2)

Hirschsprung's disease patients

Children diagnosed with Hirschsprung's disease or Hirschsprung's disease associated enterocolitis

control patients

Children diagnosed and treated for miscellaneous bowel diseases

Eligibility Criteria

Age0 Months - 18 Years
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64)
Sampling MethodNon-Probability Sample
Study Population

patients between 0 and 18 years undergoing bowel resection

You may qualify if:

  • Informed consent

You may not qualify if:

  • No signed informed consent No blood from patients with weak general state of health

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

Kinderchirurgie Universität Heidelberg

Heidelberg, 69120, Germany

Location

Ospedale Regionale di Bellinzona e Valli

Bellinzona, 6500, Switzerland

Location

Inselspital Universität Bern

Bern, 3010, Switzerland

Location

Hôpitaux Universitaires Genève

Geneva, 1205, Switzerland

Location

Bâtiment Hospitalier CHUV

Lausanne, 1011, Switzerland

Location

Luzerner Kantonsspital

Lucerne, 6000, Switzerland

Location

Kinderspital St. Gallen

Sankt Gallen, 9000, Switzerland

Location

Kinderspital Zürich

Zurich, 8032, Switzerland

Location

Related Publications (7)

  • Amiel J, Lyonnet S. Hirschsprung disease, associated syndromes, and genetics: a review. J Med Genet. 2001 Nov;38(11):729-39. doi: 10.1136/jmg.38.11.729.

    PMID: 11694544BACKGROUND

  • Demehri FR, Halaweish IF, Coran AG, Teitelbaum DH. Hirschsprung-associated enterocolitis: pathogenesis, treatment and prevention. Pediatr Surg Int. 2013 Sep;29(9):873-81. doi: 10.1007/s00383-013-3353-1.

    PMID: 23913261BACKGROUND

  • Peterson LW, Artis D. Intestinal epithelial cells: regulators of barrier function and immune homeostasis. Nat Rev Immunol. 2014 Mar;14(3):141-53. doi: 10.1038/nri3608.

    PMID: 24566914BACKGROUND

  • Curotto de Lafaille MA, Lafaille JJ. Natural and adaptive foxp3+ regulatory T cells: more of the same or a division of labor? Immunity. 2009 May;30(5):626-35. doi: 10.1016/j.immuni.2009.05.002.

    PMID: 19464985BACKGROUND

  • Cornet A, Savidge TC, Cabarrocas J, Deng WL, Colombel JF, Lassmann H, Desreumaux P, Liblau RS. Enterocolitis induced by autoimmune targeting of enteric glial cells: a possible mechanism in Crohn's disease? Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):13306-11. doi: 10.1073/pnas.231474098. Epub 2001 Oct 30.

    PMID: 11687633BACKGROUND

  • Flamant M, Aubert P, Rolli-Derkinderen M, Bourreille A, Neunlist MR, Mahe MM, Meurette G, Marteyn B, Savidge T, Galmiche JP, Sansonetti PJ, Neunlist M. Enteric glia protect against Shigella flexneri invasion in intestinal epithelial cells: a role for S-nitrosoglutathione. Gut. 2011 Apr;60(4):473-84. doi: 10.1136/gut.2010.229237. Epub 2010 Dec 7.

    PMID: 21139062BACKGROUND

  • Rusmini M, Griseri P, Lantieri F, Matera I, Hudspeth KL, Roberto A, Mikulak J, Avanzini S, Rossi V, Mattioli G, Jasonni V, Ravazzolo R, Pavan WJ, Pini-Prato A, Ceccherini I, Mavilio D. Induction of RET dependent and independent pro-inflammatory programs in human peripheral blood mononuclear cells from Hirschsprung patients. PLoS One. 2013;8(3):e59066. doi: 10.1371/journal.pone.0059066. Epub 2013 Mar 18.

    PMID: 23527089BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

* colonic tissue * blood

MeSH Terms

Conditions

Intestinal Pseudo-Obstruction

Condition Hierarchy (Ancestors)

IleusIntestinal ObstructionIntestinal DiseasesGastrointestinal DiseasesDigestive System Diseases

Study Officials

  • Stefan Holland-Cunz, Prof

    University Children's Hospital Basel

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Dr. Simone Keck

Study Record Dates

First Submitted

July 24, 2018

First Posted

August 6, 2018

Study Start

February 28, 2015

Primary Completion

February 28, 2022

Study Completion

February 28, 2022

Last Updated

November 4, 2022

Record last verified: 2022-11

Data Sharing

IPD Sharing
Will not share

Locations

CH(7)DE(1)