Hirschsprung's Advances; Working Towards Autologous tIssue therapIes

NCT06590142 | Recruiting

• 1 other identifier: 322649
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

Children with Hirschsprung's Disease (HSCR) have no normal nerve cells in the lower end of their bowel. This can cause babies to die if left untreated treated. Currently the part of bowel that doesn't have normal nerves is removed with an operation, but this can have long-term complications including needing a permanent bag on the tummy for poo (stoma). Because of this there is an urgent need for better treatments. The investigators have found that children with HSCR have nerve stem cells throughout their bowel, even in the lower end where the nerves haven't grown normally. We can grow these stem cells in the laboratory to form balls of nerve cells (neurospheres). The investigators want to find out whether these neurospheres grow into the nerves that are needed for the bowel to work normally. First the investigators will see how the nerve stem cells from the lower end of the bowel grow compared to those from the normal bowel. Then the investigators will see if the neurospheres change when the investigators put them with medications that affect growth of bowel nerves. At the end of this project the investigators hope to know whether the nerve stem cells at the lower part of the bowel in children with HSCR can turn into bowel nerve cells that might make the bowel work normally. The investigators also hope to know whether the investigators can use medications to make the stem cells turn into normal nerves, meaning that children with HSCR could avoid an operation and a stoma.

Conditions

Hirschsprung Disease

Outcome Measures

Primary Outcomes (1)

• Successful optimisation of a scRNAseq protocol using dissociated human bowel cells

  SC RNA sequencing will be successfully carried out on every specimen in which it is undertaken

  01/03/2026

Study Arms (3)

Hirschsprung's - Aganglionic

Bowel specimens will be taken from the aganglionic segment of bowel from children with Hirschsprung's disease

Procedure: Observational study of tissue specimens

Hirschsprung's - Ganglionic

Bowel specimens will be taken from the ganglionic segment of bowel from children with Hirschsprung's disease

Procedure: Observational study of tissue specimens

Control

Bowel specimens will be taken from the bowel from children who do not have Hirschsprung's disease who are undergoing bowel surgery

Procedure: Observational study of tissue specimens

Interventions

Observational study of tissue specimens PROCEDURE

No intervention will be made

Control; Hirschsprung's - Aganglionic; Hirschsprung's - Ganglionic

Eligibility Criteria

• Age: 0 Years - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

Any child undergoing therapeautic intestinal resection.

You may qualify if:

• Any child undergoing therapeutic intestinal resection (but specifically those in which it is not necessary for all resected tissue to be sent for histopathological analysis, as no additional tissue will be removed for research purposes).

You may not qualify if:

• None

Sponsors & Collaborators

• Alder Hey Children's NHS Foundation Trust: lead
• University of Liverpool: collaborator

Study Sites (1)

Alder Hey Children's NHS Foundation Trust

Liverpool, Merseyside, L12 2AP, United Kingdom

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Ganglionic samples, transition zone and aganglionic segments of bowel, addressing the following objectives: 1. Characterising neural progenitor cells in three HSCR bowel segments using transcriptomics analysis. 2. Analysing the composition of cultured neurospheres from three HSCR bowel segments using flow cytometry and qPCR. 3. Determining the differentiation potential of neural progenitor cells in neurosphere cultures by modulating key signalling pathways including Notch, Sonic Hedgehog and serotonin.

MeSH Terms

Conditions

Hirschsprung Disease

Condition Hierarchy (Ancestors)

Digestive System Abnormalities; Digestive System Diseases; Megacolon; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Central Study Contacts

Rachel Harwood, MBBS

CONTACT

01512824998; rachel.harwood@alderhey.nhs.uk

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2024
• First Posted: September 19, 2024
• Study Start: March 5, 2024
• Primary Completion (Estimated): March 1, 2034
• Study Completion (Estimated): March 1, 2036
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

GB (1)