PIPOSMOOTH-PIPONCT06687564
Role of ACTG2 Variants in Smooth Muscle Determination and Function in Pediatric Intestinal Pseudo-obstruction.
A study testing Biopsy in people with PIPO, run by University Hospital, Grenoble at 3 sites in France.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 4 years and older
- Conditions the study is for
- PIPO
- What is being tested?
- Biopsy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 3 sitesFrance
- Study dates
- 4 Feb 2026to 3 Feb 2032
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- PIPO Population:
- Minor or adult patient ≥ 4 years of age
- Patient with PIPO before age 18
- Male or female
- 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.
- Patient whose assent has been obtained and whose legal guardians have given their written informed consent
Show all 9Show fewer
- 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.
Who cannot join
- PIPO population :
- Patients with a history of radiotherapy treatment
- Patient with lymphocyte lineage damage
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
France3 sites, 3 recruiting
- Recruiting
Phymedexp Inserm U1046 - Cnrs Umr 9214
Montpellier, 34295
Pascal de Santa Barbara, Dr, 0467515234 ext. +33, Pascal.de-Santa-Barbara@inserm.fr
- Recruiting
Tens - Inserm Un Umr 1235
Nantes, 44035
Maxime Mahé, Dr, 0240412885 ext. +33, maxime.mahe@inserm.fr
- Recruiting
AP-HP Hôpital Robert Debré
Paris, 75019
Emmanuelle DUGELAY, Dr, 0140032020 ext. +33, emmanuelle.dugelay@aphp.fr
About this study
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.
Read the detailed description
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
- PIPO
- Being tested
- Biopsy
- Keywords
- PIPO, CIPO, ACTG2, pseudo-obstruction, organoid, iPS, Pediatric Intestinal Pseudo-Obstruction, Chronic Intestinal Pseudo-obstruction
- Medical subject headings
- Intestinal Pseudo-Obstruction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BiopsyProcedure or surgery
Also called Blood sample
A skin biopsy and a blood sample will be taken to culture the iPS cells and intestinal organoids.
| Study group | Role | What they receive |
|---|---|---|
| PIPO patients | Experimental | PIPO patients with variants of interest Receives: Procedure: Biopsy |
| WT | Other | Control arm, same experiments as for patients. Samples from specific cell lines Receives: Procedure: Biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Description of the transcriptional impact of R178, R257, R40 or A136 variants of the ACTG2 gene
Difference in transcript expression (%) in RNASeq transcriptomic analysis between samples carrying the R178, R257, R40 or A136 variants of the ACTG2 gene on the differentiation mechanisms of iPS up to organoids derived from PIPO patient samples versus those derived from control patients
Measured: At different stages of their experimental ex vivo development (mesenchymal progenitors, determined smooth muscle cells, differentiated smooth muscle cells and 3D organization of smooth muscle) through study completion, an average of 5 years
Secondary outcomes (5)
Evaluate the impact of R178, R257, R40 or A136 variants of the ACTG2 gene on gastrointestinal contractile function between mutant versus WT organoids.
Difference (%) in isometric contraction force between mutant versus WT organoids by electrical stimulation and specific agonist.
Measured: At different stages of their experimental ex vivo development (mesenchymal progenitors, determined smooth muscle cells, differentiated smooth muscle cells and 3D organization of smooth muscle) an average of 5 years
Evaluate the immunofluorescence labeling differential between mutant and WT cells from IPS and organoids
Difference in fluorescence (%) between mutant and WT cells as cell stages from iPS to organoids
Measured: At different stages of their experimental ex vivo development (mesenchymal progenitors, determined smooth muscle cells, differentiated smooth muscle cells and 3D organization of smooth muscle) an average of 5 years
Evaluate the impact of R178, R257, R40 or A136 mutations of the ACTG2 gene on the actin network of fibroblasts derived from skin samples of diseased patients versus those of WTpatients.
Difference in actin network labeling by immunofluorescence (%) between skin fibroblasts from PIPO and WT patients.
Measured: At different stages of their experimental ex vivo development (mesenchymal progenitors, determined smooth muscle cells, differentiated smooth muscle cells and 3D organization of smooth muscle) an average of 5 years
Evaluate the effect of reversion of the R178, R257, R40 or A136 mutation versus WT on functionality and contractility during differentiation of cells into organoids.
Difference in isometric contraction strength (%) between mutant versus WT versus revertant organoids via specific agonist and electrical stimulation.
Measured: At different stages of their experimental ex vivo development (mesenchymal progenitors, determined smooth muscle cells, differentiated smooth muscle cells and 3D organization of smooth muscle) an average of 5 years
Assessing the potential of a chemical library to correct the phenotype
Identification of molecules inducing a significant difference in isometric contraction force (%) between treated mutant organoids, untreated mutant organoids and treated and untreated WT
Measured: At different stages of their experimental ex vivo development (mesenchymal progenitors, determined smooth muscle cells, differentiated smooth muscle cells and 3D organization of smooth muscle) an average of 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2024
- Study start4 Feb 2026
- Primary completion3 Feb 2032 (estimated)
- Study completion3 Feb 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for PIPOStudies of the same condition, open and under way.
- More trials run by University Hospital, GrenobleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Model description
- Experimental, descriptive, prospective, non-randomized, controlled, comparative, monocentric in recruitment but multicentric study in procedures and analyses.
- Masking
- None (open label)
- Enrolment
- 4 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Grenoble
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06687564
- Sponsor's protocol ID
- 38RC23.0368
- Other IDs
- 2024-A01516-41
- Acronym
- SMOOTH-PIPO
- Status last verified
- May 2026
- First submitted
- 11 Oct 2024
- Last updated
- 27 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 32073506Fournier 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.
PubMed 36200034Assia 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.
PubMed 31769566de 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.
PubMed 12943221Mahe 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.
PubMed 28361322
Study at a glance
From the registry record, last updated by the sponsor on 27 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of ACTG2 Variants in Smooth Muscle Determination and Function in Pediatric Intestinal Pseudo-obstruction.
- ClinicalTrials.gov ID
- NCT06687564
- Acronym / sponsor ID
- SMOOTH-PIPO / 38RC23.0368
- Conditions
- PIPO
- Keywords
- PIPO, CIPO, ACTG2, pseudo-obstruction, organoid, iPS, Pediatric Intestinal Pseudo-Obstruction, Chronic Intestinal Pseudo-obstruction
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 4 participants (estimated)
- Lead sponsor
- University Hospital, GrenobleUniversity, hospital or other
- Study start
- 4 Feb 2026 (actual)
- Primary completion
- 3 Feb 2032 (estimated)
- Study completion
- 3 Feb 2032 (estimated)
- First posted
- 13 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Experimental, descriptive, prospective, non-randomized, controlled, comparative, monocentric in recruitment but multicentric study in procedures and analyses.
| Arm | Type | Receives |
|---|---|---|
| PIPO patients | Experimental | Procedure: BiopsyPIPO patients with variants of interest |
| WT | Other | Procedure: BiopsyControl arm, same experiments as for patients. Samples from specific cell lines |
Who may qualify
- Ages
- 4 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Minor or adult patient ≥ 4 years of age
- Patient with PIPO before age 18
- Male or female
- 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.
- Patient whose assent has been obtained and whose legal guardians have given their written informed consent
Key exclusion criteria (3 listed)
- Patients with a history of radiotherapy treatment
- Patient with lymphocyte lineage damage
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BiopsyAlso: Blood sampleA skin biopsy and a blood sample will be taken to culture the iPS cells and intestinal organoids. | Procedure or surgery | PIPO patients, WT |
Primary outcome
Description of the transcriptional impact of R178, R257, R40 or A136 variants of the ACTG2 gene
Time frame: At different stages of their experimental ex vivo development (mesenchymal progenitors, determined smooth muscle cells, differentiated smooth muscle cells and 3D organization of smooth muscle) through study completion, an average of 5 years
Difference in transcript expression (%) in RNASeq transcriptomic analysis between samples carrying the R178, R257, R40 or A136 variants of the ACTG2 gene on the differentiation mechanisms of iPS up to organoids derived from PIPO patient samples versus those derived from control patients
5 secondary outcomes
Evaluate the impact of R178, R257, R40 or A136 variants of the ACTG2 gene on gastrointestinal contractile function between mutant versus WT organoids.
Time frame: At different stages of their experimental ex vivo development (mesenchymal progenitors, determined smooth muscle cells, differentiated smooth muscle cells and 3D organization of smooth muscle) an average of 5 years
Evaluate the immunofluorescence labeling differential between mutant and WT cells from IPS and organoids
Time frame: At different stages of their experimental ex vivo development (mesenchymal progenitors, determined smooth muscle cells, differentiated smooth muscle cells and 3D organization of smooth muscle) an average of 5 years
Evaluate the impact of R178, R257, R40 or A136 mutations of the ACTG2 gene on the actin network of fibroblasts derived from skin samples of diseased patients versus those of WTpatients.
Time frame: At different stages of their experimental ex vivo development (mesenchymal progenitors, determined smooth muscle cells, differentiated smooth muscle cells and 3D organization of smooth muscle) an average of 5 years
Evaluate the effect of reversion of the R178, R257, R40 or A136 mutation versus WT on functionality and contractility during differentiation of cells into organoids.
Time frame: At different stages of their experimental ex vivo development (mesenchymal progenitors, determined smooth muscle cells, differentiated smooth muscle cells and 3D organization of smooth muscle) an average of 5 years
Assessing the potential of a chemical library to correct the phenotype
Time frame: At different stages of their experimental ex vivo development (mesenchymal progenitors, determined smooth muscle cells, differentiated smooth muscle cells and 3D organization of smooth muscle) an average of 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 May 2026.
- Background: PubMed 32073506Zenzeri 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.
- Background: PubMed 36200034Fournier 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.
- Background: PubMed 31769566Assia 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.
- Background: PubMed 12943221de 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.
- Background: PubMed 28361322Mahe 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.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Biopsy in people with PIPO, run by University Hospital, Grenoble at 3 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact John Rendu, Dr (0476765573 ext. +33, jrendu@chu-grenoble.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Description of the transcriptional impact of R178, R257, R40 or A136 variants of the ACTG2 gene (time frame: At different stages of their experimental ex vivo development (mesenchymal progenitors, determined smooth muscle cells, differentiated smooth muscle cells and 3D organization of smooth muscle) through study completion, an average of 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06687564, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 May 2026.