Arthrogryposis Multiplex CongenitaPAOLO3NCT07360574
Piezo2-related Arthrogryposis & physiopathOLOgy 3
An observational study of Arthrogryposis Multiplex Congenita and Piezo2 Mutation Gain of Function, run by University Hospital, Grenoble at 1 site in France.
Trial summary
Study type: Observational, non-interventional, single-center, descriptive study. Goal of the study: The goal of this observational study is to characterize the intensity, variability, and qualitative features of pain in patients with arthrogryposis multiplex congenita (AMC) caused by a gain-of-function mutation in… Read more about this study
- Who is it for?
- Ages 10 years and older
- Conditions the study is for
- Arthrogryposis Multiplex Congenita, Piezo2 Mutation Gain of Function
- How many people
- 12 participants
- Where
- 1 siteFrance
- Study dates
- 1 Feb 2026to Jul 2026
- How long will I take part?
- 14 Days
- Phase
- Observational
- 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 10 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients affected by Arthrogryposis Multiplex Congenita with mutation gain of function of Piezo2 gene, followed by the University Hospital of Grenoble.
Who may be able to join
- PIEZO2 mutation gain of function
- Age ≥ 10 years
- Registered member of the PARART database (Pediatric and Adult Registry for Patients With ARThrogryposis)
Who cannot join
- Age < 10 years
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site
CHU Grenoble Alpes
La Tronche, France, 38700
Klaus Dieterich, MD, Phd, 04 76 76 08 43, kdieterich@chu-grenoble.fr
kdieterich@chu-grenoble.fr
About this study
Study type: Observational, non-interventional, single-center, descriptive study.
Goal of the study:
Read more
The goal of this observational study is to characterize the intensity, variability, and qualitative features of pain in patients with arthrogryposis multiplex congenita (AMC) caused by a gain-of-function mutation in PIEZO2. This population is rare and identified through the French national PARART registry (Pediatric and Adult Registry for patients with ARThrogryposis).
Population:
Participants are ≥10 years old, have a genetically confirmed gain-of-function PIEZO2 variant, and are registered in PARART. All procedures are conducted remotely; no onsite visit is required.
Main questions the study aims to answer:
- What is the intensity and day-to-day variability of pain over 14 consecutive days, measured with a Numerical Rating Scale (0-100)?
- What are the sensory qualities and anatomical distribution of pain in this population?
- How does this pain affect quality of life?
- What treatments (pharmacological or non-pharmacological) have been used, and how effective are they?
Study design:
There is no comparison group. The study is descriptive and aims to characterize the pain phenotype linked to PIEZO2 gain-of-function mutations.
What participants will do:
Participants will complete the following tasks remotely:
At Day 1:
Questionnaires:
- Saint-Antoine Pain Questionnaire (QDSA)
- SF-12
- EQ-5D-5L
- Pain monitoring: treatments used
For 14 consecutive days (Day 1 to Day 14), on a paper logbook:
- Daily self-reported Numerical Rating Scale (NRS, 0-100) for pain
- Daily body chart to document pain distribution
All data are collected through REDCap and a paper logbook. No clinical exam, biological sampling, or hospital visit is required.
The study duration for each participant is 14 days.
Read the detailed description
Arthrogryposis multiplex congenita (AMC; Orpha code 1037) is a clinically and genetically heterogeneous group of disorders defined by congenital joint contractures affecting at least two distinct body regions (Dahan-Oliel et al. 2019).
Its estimated prevalence ranges from 1 in 3,000 to 1 in 12,000 live births, based on population-based epidemiological studies (Darin et al. 2002; Lowry et al. 2010; Hoff et al. 2012). The pathophysiology of AMC is closely linked to impaired fetal movement, with the severity of musculoskeletal manifestations depending on the timing and degree of fetal akinesia during development (Pollard, McGonnell, and Pitsillides 2014; Nowlan 2015; Felsenthal and Zelzer 2017).
Advances in molecular genetics have identified gain-of-function variants in the mechanosensitive ion channel PIEZO2 as a key etiology in a distinct subgroup of distal arthrogryposis (Coste et al. 2013). PIEZO2 plays a central role in mechanotransduction, converting mechanical stimuli into ionic currents in peripheral sensory neurons, thereby mediating proprioception and mechanical nociception (Wu, Lewis, and Grandl 2017; Szczot et al. 2021; Ma et al. 2023; Sánchez-Carranza et al. 2024).
Structural studies have shown that PIEZO2 forms a large trimeric propeller-shaped mechanosensitive channel whose architecture enables rapid transduction of membrane tension into cation influx, particularly Na⁺ and Ca²⁺ (Wang et al. 2019). Experimental data indicate that PIEZO2 gain-of-function mutations lead to delayed channel inactivation, neuronal hyperexcitability, and aberrant mechanotransduction, which likely underlie the distinctive pain phenotype observed in affected patients (Coste et al. 2013).
Clinically, individuals with PIEZO2-related AMC frequently report chronic diffuse pain with episodic exacerbations that are often poorly responsive to conventional analgesic strategies. Despite this recognizable pattern, genotype-phenotype correlations and the mechanisms driving pain severity and distribution remain insufficiently characterized.
This single-center, non-interventional observational study aims to describe the pain phenotype of individuals with AMC caused by gain-of-function variants in PIEZO2 identified through the national PARART registry (NCT05673265).
The study consists of prospective remote collection of self-reported outcomes using validated questionnaires. On Day 1, participants complete assessments of pain quality (QDSA) and quality of life (SF-12 and EQ-5D-5L), along with documentation of prior analgesic strategies. From Day 1 to Day 14, participants record daily pain intensity using a Numerical Rating Scale (0-100) and pain localization on a body chart, enabling evaluation of pain intensity, temporal variability, and anatomical distribution.
The study relies exclusively on descriptive statistical analyses, without hypothesis testing or comparison groups. Data are collected and managed using REDCap, in accordance with predefined procedures for pseudonymization, data integrity, and regulatory compliance (Harris et al. 2009; Harris et al. 2019). By systematically characterizing pain features and their impact on quality of life, this study seeks to improve understanding of the clinical pain profile associated with PIEZO2 gain-of-function mutations and to provide a foundation for future mechanism-based therapeutic strategies in this rare condition.
- Keywords
- Arthrogyposis, Piezo2
- Medical subject headings
- Arthrogryposis
What is being measured
The primary outcome is the main question the study is designed to answer.
Numeric Rating Scale
Quantitative Pain Evaluation : scale from 0 (no pain) to 100 (worst pain ever).
Measured: From the start to the end of the follow-up at 14 days
Secondary outcomes (5)
Body Pain Map
Location of the pain on the body.
Measured: From the start to the end of the follow-up at 14 days
EuroQol 5-Dimensions 5-Levels
Self-questionnaire to evaluate the quality of life. 5D : Five Dimensions (Mobility, Self-Care, Usual Activities, Pain/Discomfort, Anxiety/Depression).
5L : Five Levels (No problems, Slight, Moderate, Severe, Extreme problems)
Measured: At the start of the follow-up (Day 1).
12-Item Short Form Health Survey
The SF-12 is a self-reported questionnaire that produces two summary scores: the Physical Component Summary (PCS) and the Mental Component Summary (MCS).
Measured: At the start of the follow-up (Day 1).
Saint-Antoine Pain Questionnaire
Qualitative description of pain with a variety of words refering to the different pain types, in distinct groups.
Measured: At the start of the follow-up (Day 1).
Pain Monitoring / Treatments
Listing of pain treatments (medicinal or non-medicinal) used by the patient.
Measured: At the start of the follow-up (Day 1).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2026
- Study start1 Feb 2026 (estimated)
- Primary completionJul 2026 (estimated)
- Study completionJul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Arthrogryposis Multiplex CongenitaStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 12 participants (estimated)
- Target duration
- 14 Days
Sponsor and investigators
- Lead sponsor
- University Hospital, Grenoble
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07360574
- Sponsor's protocol ID
- 38RC25.0314
- Acronym
- PAOLO3
- Status last verified
- Jan 2026
- First submitted
- 15 Dec 2025
- Last updated
- 22 Jan 2026
- Results posted
- No
- Individual data sharing
- No: Individual participant data will not be shared due to ethical and regulatory constraints, and because no data-sharing plan is defined in the study protocol.
Publications
Coste B, Houge G, Murray MF, Stitziel N, Bandell M, Giovanni MA, Philippakis A, Hoischen A, Riemer G, Steen U, Steen VM, Mathur J, Cox J, Lebo M, Rehm H, Weiss ST, Wood JN, Maas RL, Sunyaev SR, Patapoutian A. Gain-of-function mutations in the mechanically activated ion channel PIEZO2 cause a subtype of Distal Arthrogryposis. Proc Natl Acad Sci U S A. 2013 Mar 19;110(12):4667-72. doi: 10.1073/pnas.1221400110. Epub 2013 Mar 4.
PubMed 23487782Felsenthal N, Zelzer E. Mechanical regulation of musculoskeletal system development. Development. 2017 Dec 1;144(23):4271-4283. doi: 10.1242/dev.151266.
PubMed 29183940Nowlan NC. Biomechanics of foetal movement. Eur Cell Mater. 2015 Jan 2;29:1-21; discussion 21. doi: 10.22203/ecm.v029a01.
PubMed 25552425Pollard AS, McGonnell IM, Pitsillides AA. Mechanoadaptation of developing limbs: shaking a leg. J Anat. 2014 Jun;224(6):615-23. doi: 10.1111/joa.12171. Epub 2014 Mar 18.
PubMed 24635640Hoff JM, Loane M, Gilhus NE, Rasmussen S, Daltveit AK. Arthrogryposis multiplexa congenita: an epidemiologic study of nearly 9 million births in 24 EUROCAT registers. Eur J Obstet Gynecol Reprod Biol. 2011 Dec;159(2):347-50. doi: 10.1016/j.ejogrb.2011.09.027. Epub 2011 Oct 17.
PubMed 22005589Lowry RB, Sibbald B, Bedard T, Hall JG. Prevalence of multiple congenital contractures including arthrogryposis multiplex congenita in Alberta, Canada, and a strategy for classification and coding. Birth Defects Res A Clin Mol Teratol. 2010 Dec;88(12):1057-61. doi: 10.1002/bdra.20738. Epub 2010 Nov 15.
PubMed 21157886Darin N, Kimber E, Kroksmark AK, Tulinius M. Multiple congenital contractures: birth prevalence, etiology, and outcome. J Pediatr. 2002 Jan;140(1):61-7. doi: 10.1067/mpd.2002.121148.
PubMed 11815765Dahan-Oliel N, Cachecho S, Barnes D, Bedard T, Davison AM, Dieterich K, Donohoe M, Fafara A, Hamdy R, Hjartarson HT, S Hoffman N, Kimber E, Komolkin I, Lester R, Ponten E, van Bosse HJP, Hall JG. International multidisciplinary collaboration toward an annotated definition of arthrogryposis multiplex congenita. Am J Med Genet C Semin Med Genet. 2019 Sep;181(3):288-299. doi: 10.1002/ajmg.c.31721. Epub 2019 Jul 7.
PubMed 31282072
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Piezo2-related Arthrogryposis & physiopathOLOgy 3
- ClinicalTrials.gov ID
- NCT07360574
- Acronym / sponsor ID
- PAOLO3 / 38RC25.0314
- Keywords
- Arthrogyposis, Piezo2
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- University Hospital, GrenobleUniversity, hospital or other
- Study start
- 1 Feb 2026 (estimated)
- Primary completion
- Jul 2026 (estimated)
- Study completion
- Jul 2026 (estimated)
- First posted
- 22 Jan 2026 (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.
Study type: Observational, non-interventional, single-center, descriptive study.
Goal of the study:
The goal of this observational study is to characterize the intensity, variability, and qualitative features of pain in patients with arthrogryposis multiplex congenita (AMC) caused by a gain-of-function mutation in PIEZO2. This population is rare and identified through the French national PARART registry (Pediatric and Adult Registry for patients with ARThrogryposis).
Population:
Participants are ≥10 years old, have a genetically confirmed gain-of-function PIEZO2 variant, and are registered in PARART. All procedures are conducted remotely; no onsite visit is required.
Main questions the study aims to answer:
- What is the intensity and day-to-day variability of pain over 14 consecutive days, measured with a Numerical Rating Scale (0-100)?
- What are the sensory qualities and anatomical distribution of pain in this population?
- How does this pain affect quality of life?
- What treatments (pharmacological or non-pharmacological) have been used, and how effective are they?
Study design:
There is no comparison group. The study is descriptive and aims to characterize the pain phenotype linked to PIEZO2 gain-of-function mutations.
What participants will do:
Participants will complete the following tasks remotely:
At Day 1:
Questionnaires:
- Saint-Antoine Pain Questionnaire (QDSA)
- SF-12
- EQ-5D-5L
- Pain monitoring: treatments used
For 14 consecutive days (Day 1 to Day 14), on a paper logbook:
- Daily self-reported Numerical Rating Scale (NRS, 0-100) for pain
- Daily body chart to document pain distribution
All data are collected through REDCap and a paper logbook. No clinical exam, biological sampling, or hospital visit is required.
The study duration for each participant is 14 days.
Detailed description
Arthrogryposis multiplex congenita (AMC; Orpha code 1037) is a clinically and genetically heterogeneous group of disorders defined by congenital joint contractures affecting at least two distinct body regions (Dahan-Oliel et al. 2019).
Its estimated prevalence ranges from 1 in 3,000 to 1 in 12,000 live births, based on population-based epidemiological studies (Darin et al. 2002; Lowry et al. 2010; Hoff et al. 2012). The pathophysiology of AMC is closely linked to impaired fetal movement, with the severity of musculoskeletal manifestations depending on the timing and degree of fetal akinesia during development (Pollard, McGonnell, and Pitsillides 2014; Nowlan 2015; Felsenthal and Zelzer 2017).
Advances in molecular genetics have identified gain-of-function variants in the mechanosensitive ion channel PIEZO2 as a key etiology in a distinct subgroup of distal arthrogryposis (Coste et al. 2013). PIEZO2 plays a central role in mechanotransduction, converting mechanical stimuli into ionic currents in peripheral sensory neurons, thereby mediating proprioception and mechanical nociception (Wu, Lewis, and Grandl 2017; Szczot et al. 2021; Ma et al. 2023; Sánchez-Carranza et al. 2024).
Structural studies have shown that PIEZO2 forms a large trimeric propeller-shaped mechanosensitive channel whose architecture enables rapid transduction of membrane tension into cation influx, particularly Na⁺ and Ca²⁺ (Wang et al. 2019). Experimental data indicate that PIEZO2 gain-of-function mutations lead to delayed channel inactivation, neuronal hyperexcitability, and aberrant mechanotransduction, which likely underlie the distinctive pain phenotype observed in affected patients (Coste et al. 2013).
Clinically, individuals with PIEZO2-related AMC frequently report chronic diffuse pain with episodic exacerbations that are often poorly responsive to conventional analgesic strategies. Despite this recognizable pattern, genotype-phenotype correlations and the mechanisms driving pain severity and distribution remain insufficiently characterized.
This single-center, non-interventional observational study aims to describe the pain phenotype of individuals with AMC caused by gain-of-function variants in PIEZO2 identified through the national PARART registry (NCT05673265).
The study consists of prospective remote collection of self-reported outcomes using validated questionnaires. On Day 1, participants complete assessments of pain quality (QDSA) and quality of life (SF-12 and EQ-5D-5L), along with documentation of prior analgesic strategies. From Day 1 to Day 14, participants record daily pain intensity using a Numerical Rating Scale (0-100) and pain localization on a body chart, enabling evaluation of pain intensity, temporal variability, and anatomical distribution.
The study relies exclusively on descriptive statistical analyses, without hypothesis testing or comparison groups. Data are collected and managed using REDCap, in accordance with predefined procedures for pseudonymization, data integrity, and regulatory compliance (Harris et al. 2009; Harris et al. 2019). By systematically characterizing pain features and their impact on quality of life, this study seeks to improve understanding of the clinical pain profile associated with PIEZO2 gain-of-function mutations and to provide a foundation for future mechanism-based therapeutic strategies in this rare condition.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 14 Days
Who may qualify
- Ages
- 10 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients affected by Arthrogryposis Multiplex Congenita with mutation gain of function of Piezo2 gene, followed by the University Hospital of Grenoble.
Key inclusion criteria (3 listed)
- PIEZO2 mutation gain of function
- Age ≥ 10 years
- Registered member of the PARART database (Pediatric and Adult Registry for Patients With ARThrogryposis)
Key exclusion criteria (1 listed)
- Age < 10 years
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Numeric Rating Scale
Time frame: From the start to the end of the follow-up at 14 days
Quantitative Pain Evaluation : scale from 0 (no pain) to 100 (worst pain ever).
5 secondary outcomes
Body Pain Map
Time frame: From the start to the end of the follow-up at 14 days
EuroQol 5-Dimensions 5-Levels
Time frame: At the start of the follow-up (Day 1).
12-Item Short Form Health Survey
Time frame: At the start of the follow-up (Day 1).
Saint-Antoine Pain Questionnaire
Time frame: At the start of the follow-up (Day 1).
Pain Monitoring / Treatments
Time frame: At the start of the follow-up (Day 1).
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 22 Jan 2026.
- Background: PubMed 23487782Coste B, Houge G, Murray MF, Stitziel N, Bandell M, Giovanni MA, Philippakis A, Hoischen A, Riemer G, Steen U, Steen VM, Mathur J, Cox J, Lebo M, Rehm H, Weiss ST, Wood JN, Maas RL, Sunyaev SR, Patapoutian A. Gain-of-function mutations in the mechanically activated ion channel PIEZO2 cause a subtype of Distal Arthrogryposis. Proc Natl Acad Sci U S A. 2013 Mar 19;110(12):4667-72. doi: 10.1073/pnas.1221400110. Epub 2013 Mar 4.
- Background: PubMed 29183940Felsenthal N, Zelzer E. Mechanical regulation of musculoskeletal system development. Development. 2017 Dec 1;144(23):4271-4283. doi: 10.1242/dev.151266.
- Background: PubMed 25552425Nowlan NC. Biomechanics of foetal movement. Eur Cell Mater. 2015 Jan 2;29:1-21; discussion 21. doi: 10.22203/ecm.v029a01.
- Background: PubMed 24635640Pollard AS, McGonnell IM, Pitsillides AA. Mechanoadaptation of developing limbs: shaking a leg. J Anat. 2014 Jun;224(6):615-23. doi: 10.1111/joa.12171. Epub 2014 Mar 18.
- Background: PubMed 22005589Hoff JM, Loane M, Gilhus NE, Rasmussen S, Daltveit AK. Arthrogryposis multiplexa congenita: an epidemiologic study of nearly 9 million births in 24 EUROCAT registers. Eur J Obstet Gynecol Reprod Biol. 2011 Dec;159(2):347-50. doi: 10.1016/j.ejogrb.2011.09.027. Epub 2011 Oct 17.
- Background: PubMed 21157886Lowry RB, Sibbald B, Bedard T, Hall JG. Prevalence of multiple congenital contractures including arthrogryposis multiplex congenita in Alberta, Canada, and a strategy for classification and coding. Birth Defects Res A Clin Mol Teratol. 2010 Dec;88(12):1057-61. doi: 10.1002/bdra.20738. Epub 2010 Nov 15.
- Background: PubMed 11815765Darin N, Kimber E, Kroksmark AK, Tulinius M. Multiple congenital contractures: birth prevalence, etiology, and outcome. J Pediatr. 2002 Jan;140(1):61-7. doi: 10.1067/mpd.2002.121148.
- Background: PubMed 31282072Dahan-Oliel N, Cachecho S, Barnes D, Bedard T, Davison AM, Dieterich K, Donohoe M, Fafara A, Hamdy R, Hjartarson HT, S Hoffman N, Kimber E, Komolkin I, Lester R, Ponten E, van Bosse HJP, Hall JG. International multidisciplinary collaboration toward an annotated definition of arthrogryposis multiplex congenita. Am J Med Genet C Semin Med Genet. 2019 Sep;181(3):288-299. doi: 10.1002/ajmg.c.31721. Epub 2019 Jul 7.
- Individual participant dataSharing planned: No. Individual participant data will not be shared due to ethical and regulatory constraints, and because no data-sharing plan is defined in the study protocol.
Related trials for Arthrogryposis Multiplex Congenita
Recruiting
Technical Feasibility Study of Ultrasound Muscle Imaging in Antenatal Ultrasound
Arthrogryposis Multiplex Congenita (AMC)
Enrolling by invitation
Palliative Care Needs of Children With Rare Diseases and Their Families
Trisomy 13 Syndrome, Arthrogryposis Congenita Multiplex With Intestinal Atresia
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Arthrogryposis Multiplex Congenita and Piezo2 Mutation Gain of Function, run by University Hospital, Grenoble at 1 site 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 3 inclusion and 1 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: opening soon, as of the sponsor's last update on 22 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Numeric Rating Scale (time frame: From the start to the end of the follow-up at 14 days). 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 NCT07360574, which also lists 8 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 22 Jan 2026.