Role of ACTG2 Variants in Smooth Muscle Determination and Function in Pediatric Intestinal Pseudo-obstruction.

NCT ID: NCT06687564

Last Updated: 2025-01-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

4 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-02-28

Study Completion Date

2030-11-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The primary objective of this study is to describe the transcriptional impact of R178, R257, R40 or A136 variants of the ACTG2 gene on iPS differentiation mechanisms up to organoids derived from PIPO patient samples versus those derived from control / WT patients (generation of IPS from cultured cell lines), at different stages of their experimental ex vivo development.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Recruited patients will be sampled during a consultation: a blood sample and a biopsy will be taken directly from the patient. Once these samples have been taken, they will be cultured to be reprogrammed into iPS cells, then grown and differentiated into intestinal organoids.

Various experiments will be carried out (as described in the outcomes) to identify at molecular, cellular and tissue level the mechanisms altered in patients with an R178, R257, R40 or A136 variant, assessing their consequence(s) on the development and functionality of the digestive mesenchyme.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

PIPO

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

FACTORIAL

Experimental, descriptive, prospective, non-randomized, controlled, comparative, monocentric in recruitment but multicentric study in procedures and analyses.
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

PIPO patients

PIPO patients with variants of interest

Group Type EXPERIMENTAL

Biopsy

Intervention Type PROCEDURE

A skin biopsy and a blood sample will be taken to culture the iPS cells and intestinal organoids.

WT

Control arm, same experiments as for patients. Samples from specific cell lines

Group Type OTHER

Biopsy

Intervention Type PROCEDURE

A skin biopsy and a blood sample will be taken to culture the iPS cells and intestinal organoids.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Biopsy

A skin biopsy and a blood sample will be taken to culture the iPS cells and intestinal organoids.

Intervention Type PROCEDURE

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Blood sample

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

PIPO Population:

1. Minor or adult patient ≥ 4 years of age
2. Patient with PIPO before age 18
3. Male or female
4. Patient with PIPO meeting at least 2 of the ESPGHAN criteria (Thapar et al 2018) and carrying the R178, R257, R40 or A136 mutation of the ACTG2 gene.
5. Patient whose assent has been obtained and whose legal guardians have given their written informed consent
6. Patient affiliated to the French Social Security system or benefiting from an equivalent plan

WT population:

\- iPS cell lines MS573 or WT8288 or 202CT or SD378M, from the Nantes University Hospital biological collection and generated from samples from control patients without POIC who have consented to donate their samples.

Exclusion Criteria

PIPO population :

1. Patients with a history of radiotherapy treatment
2. Patient with lymphocyte lineage damage
Minimum Eligible Age

4 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

University Hospital, Grenoble

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Phymedexp Inserm U1046 - Cnrs Umr 9214

Montpellier, , France

Site Status

Tens - Inserm Un Umr 1235

Nantes, , France

Site Status

AP-HP Hôpital Robert Debré

Paris, , France

Site Status

Countries

Review the countries where the study has at least one active or historical site.

France

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

John Rendu, Dr

Role: CONTACT

0476765573 ext. +33

Mandy Leger

Role: CONTACT

0476768410 ext. +33

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Pascal de Santa Barbara, Dr

Role: primary

0467515234 ext. +33

Maxime Mahé, Dr

Role: primary

0240412885 ext. +33

Emmanuelle DUGELAY, Dr

Role: primary

0140032020 ext. +33

References

Explore related publications, articles, or registry entries linked to this study.

Zenzeri L, Tambucci R, Quitadamo P, Giorgio V, De Giorgio R, Di Nardo G. Update on chronic intestinal pseudo-obstruction. Curr Opin Gastroenterol. 2020 May;36(3):230-237. doi: 10.1097/MOG.0000000000000630.

Reference Type BACKGROUND
PMID: 32073506 (View on PubMed)

Fournier N, Fabre A. Smooth muscle motility disorder phenotypes: A systematic review of cases associated with seven pathogenic genes (ACTG2, MYH11, FLNA, MYLK, RAD21, MYL9 and LMOD1). Intractable Rare Dis Res. 2022 Aug;11(3):113-119. doi: 10.5582/irdr.2022.01060.

Reference Type BACKGROUND
PMID: 36200034 (View on PubMed)

Assia Batzir N, Kishor Bhagwat P, Larson A, Coban Akdemir Z, Baglaj M, Bofferding L, Bosanko KB, Bouassida S, Callewaert B, Cannon A, Enchautegui Colon Y, Garnica AD, Harr MH, Heck S, Hurst ACE, Jhangiani SN, Isidor B, Littlejohn RO, Liu P, Magoulas P, Mar Fan H, Marom R, McLean S, Nezarati MM, Nugent KM, Petersen MB, Rocha ML, Roeder E, Smigiel R, Tully I, Weisfeld-Adams J, Wells KO; Baylor-Hopkins Center for Mendelian Genomics; Posey JE, Lupski JR, Beaudet AL, Wangler MF. Recurrent arginine substitutions in the ACTG2 gene are the primary driver of disease burden and severity in visceral myopathy. Hum Mutat. 2020 Mar;41(3):641-654. doi: 10.1002/humu.23960. Epub 2019 Dec 19.

Reference Type BACKGROUND
PMID: 31769566 (View on PubMed)

de Santa Barbara P, van den Brink GR, Roberts DJ. Development and differentiation of the intestinal epithelium. Cell Mol Life Sci. 2003 Jul;60(7):1322-32. doi: 10.1007/s00018-003-2289-3.

Reference Type BACKGROUND
PMID: 12943221 (View on PubMed)

Mahe MM, Brown NE, Poling HM, Helmrath MA. In Vivo Model of Small Intestine. Methods Mol Biol. 2017;1597:229-245. doi: 10.1007/978-1-4939-6949-4_17.

Reference Type BACKGROUND
PMID: 28361322 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2024-A01516-41

Identifier Type: OTHER

Identifier Source: secondary_id

38RC23.0368

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.