Ehlers-Danlos SyndromeREDNCT04133272
Registry of Ehlers-Danlos Syndrome
An observational study of Ehlers-Danlos Syndrome, run by Luca Sangiorgi at 1 site in Italy.
Trial summary
RED is a retrospective and prospective registry, finalized for care and research purposes. It is articulated in main sections - strongly related and mutually dependent on each other - corresponding to different data domains: personal information, clinical data, genetic data, genealogical data, surgeries, etc. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Ehlers-Danlos Syndrome
- How many people
- 3,000 participants
- Where
- 1 siteItaly
- Study dates
- Jun 2014to Jan 2033
- How long will I take part?
- 25 Years
- 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 Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Patients affected by Ehlers-Danlos Syndrome. The Registry will include also data on fetuses (prenatal and abortion)
Who may be able to join
- All Ehlers-Danlos Syndrome patients, including prenatal and fetal diagnosis of Ehlers-Danlos Syndrome
Who cannot join
- Any condition unrelated to Ehlers-Danlos Syndrome
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Irccs Istituto Ortopedico Rizzoli
Bologna, Emilia-Romagna, 40136
Marina Mordenti, PhD, +39 051 6366062, registri.malattierare@ior.it
Marcella Lanza, PhD, +39 051 6366169, registri.malattierare@ior.it
About this study
Official title: Registry of Ehlers-Danlos Syndrome That Collects Clinical, Functional, Genetic, Genealogical, Imaging, Surgical, Treatment, Quality of Life Data. Data Are Linked to Patients' Biological Samples, When Available
RED is a retrospective and prospective registry, finalized for care and research purposes. It is articulated in main sections - strongly related and mutually dependent on each other - corresponding to different data domains: personal information, clinical data, genetic data, genealogical data, surgeries, etc.
This approach has been developed to corroborate and integrate data from different sources and evaluating several aspects of diseases and to correlate genetic background and phenotypic outcomes, in order to better investigate disease pathophysiology. Due to legal requirements, institutional directives and organizational issues, we are unable to include individuals residing outside Italy in the registry at this time. We are currently engaged in the preparation of a recruitment process for individuals residing outside Italy.
Read the detailed description
The traditional method of collecting patient information is often chaotic, inconvenient and sometimes even unsafe, particularly when dealing with rare diseases. In 2014, the need to simplify the diagnostic process and to overcome the difficulties of data storage and analysis, led to the suggestion of implementing the Registry of Ehlers-Danlos Syndrome (RED).
The RED relies on an IT platform named Genotype-phenotype Data Integration platform - GeDI. This solution was developed through a collaboration between Rare Skeletal Disease Department and a local software company (Dilaxia) and is General Data Protection Regulation (GDPR)-compliant, multi-client and web-accessible. It has been designed according to current medical informatics standards, including the Orphanet code, the International Classification of Diseases (ICD), the Human Genome Variants Society, aiming to follow FAIR (Findability Accessibility Interoperability Reusability) principles. GeDI is continuously being implemented to improve the management of people with Ehlers-Danlos Syndrome and to assist researchers in analysing the information collected. RED is divided into the following main sections:
- Personal data: it comprises general information, birth details and residence data;
- Patient data: including the patients internal code, the hospital code and other patient details;
- Diagnostic Process: the diagnosis, the status (affected, suspected, etc.), age at diagnosis, comorbidities, allergies, etc.;
- Genogram: a tool for designing the family transmission of the disease, alongside information on the disease status of all relatives included;
- Clinical events: it records a long list of signs and symptoms of Ehlers-Danlos Syndrome as well as several additional items to describe the disease
- Genetic Analysis and Alteration: including analytical technique, sample information, analysis duration, etc. This section also comprises detailed information on any detected pathological variants (e.g. gene, international reference, DNA change, protein change, genomic position, etc.);
- Visits: this section includes visit type (genetic, orthopedic, rehabilitation, pediatric, etc.), the date of the visit, prescriptions, imaging, etc.;
- Treatments: this section comprises information of a wide range of treatments including pharmacological, devices, supplements, and other treatments such as psychological, nutritional, etc.;
- Surgeries: this section contains information on the type of surgeries, the age of the patients, the site/localization of the procedures, etc.
- Documents: this repository allow us to store all types of documents (radiological reports, imaging, consents, clinical reports, etc.);
- Consents: this section provides a comprehensive overview of all consents collected, including the collection date;
- Samples: this section includes information on the samples, like the type, date of collection, etc.
- PROs: this section collects information on patients reported outcomes such as the quality of life or ABC scale.
- Conditions
- Ehlers-Danlos Syndrome
- Keywords
- Disease Registry, Natural History Study, Disease Evolution, Genotype-Phenotype Correlation
- Medical subject headings
- Ehlers-Danlos Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Ehlers-Danlos Syndrome patients | The group comprises all patients affected by Ehlers-Danlos Syndrome, including prenatal and fetal diagnosis of Ehlers-Danlos Syndrome |
What is being measured
The primary outcome is the main question the study is designed to answer.
Natural History and Epidemiology in terms of clinical, genetic and functional evaluation
To maintain an established registry in order to assess epidemiology and natural history.
Collection of:
- physical examinations data: assessment of type of the disease (according to Orphanet types)
- orthopedic and functional data: stature (cm), weight (kg), Beighton score, pain score (numeric scale), presence cardiac lesion (ultrasound)
- surgical procedures: type, number and site of surgeries disease-related and age at surgeries
- genetics background: target gene, type of mutation, type of variant detected, clinical significance
- family history: inheritance in maternal or paternal line
- treatment information: pharmacological, devices, supplements, and other treatments
Clinical, orthopedic, surgical, treatment and functional features are updated at each follow up. Clinical reports, medical charts, genetic report and imaging are the primary sources of data.
Measured: 25 years
Secondary outcomes (1)
Genotype-Phenotype Correlation among clinical features and molecular background
The secondary outcome comprises the correlation between genotype and phenotype. This includes but is not limited to clinical features and genetic background. This will be pursued using the information collected during visits and follow-ups and the genetic information resulting from molecular investigations
Measured: 25 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2019
- Study startJun 2014
- Primary completionJun 2027 (estimated)
- Study completionJan 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Ehlers-Danlos SyndromeStudies of the same condition, open and under way.
- 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
- Other
- Enrolment
- 3,000 participants (estimated)
- Target duration
- 25 Years
Sponsor and investigators
- Lead sponsor
- Luca Sangiorgi
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Luca Sangiorgi, Istituto Ortopedico Rizzoli
- Investigators
- Luca Sangiorgi, MD, PhD, MS, Principal investigator, Istituto Ortopedico Rizzoli
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04133272
- Sponsor's protocol ID
- 21611/2014
- Acronym
- RED
- Status last verified
- Nov 2026
- First submitted
- 14 Oct 2019
- Last updated
- 5 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Ritelli M, Rovati C, Venturini M, Chiarelli N, Cinquina V, Castori M, Colombi M. Application of the 2017 criteria for vascular Ehlers-Danlos syndrome in 50 patients ascertained according to the Villefranche nosology. Clin Genet. 2020 Feb;97(2):287-295. doi: 10.1111/cge.13653. Epub 2019 Nov 3.
PubMed 31600821Ghali N, Sobey G, Burrows N. Ehlers-Danlos syndromes. BMJ. 2019 Sep 18;366:l4966. doi: 10.1136/bmj.l4966. No abstract available.
PubMed 31533917Black CM, Gathercole LJ, Bailey AJ, Beighton P. The Ehlers-Danlos syndrome: an analysis of the structure of the collagen fibres of the skin. Br J Dermatol. 1980 Jan;102(1):85-96. doi: 10.1111/j.1365-2133.1980.tb05675.x.
PubMed 7378285Beighton P. Ehlers-Danlos syndrome. Ann Rheum Dis. 1970 May;29(3):332-3. doi: 10.1136/ard.29.3.332. No abstract available.
PubMed 5432600Benistan K, Gillas F. Pain in Ehlers-Danlos syndromes. Joint Bone Spine. 2020 May;87(3):199-201. doi: 10.1016/j.jbspin.2019.09.011. Epub 2019 Sep 25. No abstract available.
PubMed 31562935Hausser I. Diagnosis of Ehlers-Danlos syndrome: data deficiency still does not allow establishment of a complete history of the disease and its pathomechanisms. Br J Dermatol. 2020 Mar;182(3):535-536. doi: 10.1111/bjd.18373. Epub 2019 Aug 20. No abstract available.
PubMed 31432500Jesudas R, Chaudhury A, Laukaitis CM. An update on the new classification of Ehlers-Danlos syndrome and review of the causes of bleeding in this population. Haemophilia. 2019 Jul;25(4):558-566. doi: 10.1111/hae.13800. Epub 2019 Jun 10.
PubMed 31329366De Baets S, Calders P, Verhoost L, Coussens M, Dewandele I, Malfait F, Vanderstraeten G, Van Hove G, Van de Velde D. Patient perspectives on employment participation in the "hypermobile Ehlers-Danlos syndrome". Disabil Rehabil. 2021 Mar;43(5):668-677. doi: 10.1080/09638288.2019.1636316. Epub 2019 Jul 9.
PubMed 31287330Copetti M, Morlino S, Colombi M, Grammatico P, Fontana A, Castori M. Severity classes in adults with hypermobile Ehlers-Danlos syndrome/hypermobility spectrum disorders: a pilot study of 105 Italian patients. Rheumatology (Oxford). 2019 Oct 1;58(10):1722-1730. doi: 10.1093/rheumatology/kez029.
PubMed 30783660Mu W, Muriello M, Clemens JL, Wang Y, Smith CH, Tran PT, Rowe PC, Francomano CA, Kline AD, Bodurtha J. Factors affecting quality of life in children and adolescents with hypermobile Ehlers-Danlos syndrome/hypermobility spectrum disorders. Am J Med Genet A. 2019 Apr;179(4):561-569. doi: 10.1002/ajmg.a.61055. Epub 2019 Jan 31.
PubMed 30703284Morri M, Tremosini M, Forni C, Moroni A, Pedrini E, Cecco AD, Gnoli M, Sangiorgi L. Characteristics of Pain in Patients Diagnosed With Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders. An Observational Study. Pain Res Manag. 2026;2026(1):e6664142. doi: 10.1155/prm/6664142.
PubMed 42363793
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Registry of Ehlers-Danlos Syndrome That Collects Clinical, Functional, Genetic, Genealogical, Imaging, Surgical, Treatment, Quality of Life Data. Data Are Linked to Patients' Biological Samples, When Available
- ClinicalTrials.gov ID
- NCT04133272
- Acronym / sponsor ID
- RED / 21611/2014
- Conditions
- Ehlers-Danlos Syndrome
- Keywords
- Disease Registry, Natural History Study, Disease Evolution, Genotype-Phenotype Correlation
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 3,000 participants (estimated)
- Lead sponsor
- Luca SangiorgiUniversity, hospital or other
- Study start
- Jun 2014 (actual)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Jan 2033 (estimated)
- First posted
- 21 Oct 2019 (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.
RED is a retrospective and prospective registry, finalized for care and research purposes. It is articulated in main sections - strongly related and mutually dependent on each other - corresponding to different data domains: personal information, clinical data, genetic data, genealogical data, surgeries, etc.
This approach has been developed to corroborate and integrate data from different sources and evaluating several aspects of diseases and to correlate genetic background and phenotypic outcomes, in order to better investigate disease pathophysiology. Due to legal requirements, institutional directives and organizational issues, we are unable to include individuals residing outside Italy in the registry at this time. We are currently engaged in the preparation of a recruitment process for individuals residing outside Italy.
Detailed description
The traditional method of collecting patient information is often chaotic, inconvenient and sometimes even unsafe, particularly when dealing with rare diseases. In 2014, the need to simplify the diagnostic process and to overcome the difficulties of data storage and analysis, led to the suggestion of implementing the Registry of Ehlers-Danlos Syndrome (RED).
The RED relies on an IT platform named Genotype-phenotype Data Integration platform - GeDI. This solution was developed through a collaboration between Rare Skeletal Disease Department and a local software company (Dilaxia) and is General Data Protection Regulation (GDPR)-compliant, multi-client and web-accessible. It has been designed according to current medical informatics standards, including the Orphanet code, the International Classification of Diseases (ICD), the Human Genome Variants Society, aiming to follow FAIR (Findability Accessibility Interoperability Reusability) principles. GeDI is continuously being implemented to improve the management of people with Ehlers-Danlos Syndrome and to assist researchers in analysing the information collected. RED is divided into the following main sections:
- Personal data: it comprises general information, birth details and residence data;
- Patient data: including the patients internal code, the hospital code and other patient details;
- Diagnostic Process: the diagnosis, the status (affected, suspected, etc.), age at diagnosis, comorbidities, allergies, etc.;
- Genogram: a tool for designing the family transmission of the disease, alongside information on the disease status of all relatives included;
- Clinical events: it records a long list of signs and symptoms of Ehlers-Danlos Syndrome as well as several additional items to describe the disease
- Genetic Analysis and Alteration: including analytical technique, sample information, analysis duration, etc. This section also comprises detailed information on any detected pathological variants (e.g. gene, international reference, DNA change, protein change, genomic position, etc.);
- Visits: this section includes visit type (genetic, orthopedic, rehabilitation, pediatric, etc.), the date of the visit, prescriptions, imaging, etc.;
- Treatments: this section comprises information of a wide range of treatments including pharmacological, devices, supplements, and other treatments such as psychological, nutritional, etc.;
- Surgeries: this section contains information on the type of surgeries, the age of the patients, the site/localization of the procedures, etc.
- Documents: this repository allow us to store all types of documents (radiological reports, imaging, consents, clinical reports, etc.);
- Consents: this section provides a comprehensive overview of all consents collected, including the collection date;
- Samples: this section includes information on the samples, like the type, date of collection, etc.
- PROs: this section collects information on patients reported outcomes such as the quality of life or ABC scale.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Target follow-up
- 25 Years
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ehlers-Danlos Syndrome patients | – | –The group comprises all patients affected by Ehlers-Danlos Syndrome, including prenatal and fetal diagnosis of Ehlers-Danlos Syndrome |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients affected by Ehlers-Danlos Syndrome. The Registry will include also data on fetuses (prenatal and abortion)
Key inclusion criteria (1 listed)
- All Ehlers-Danlos Syndrome patients, including prenatal and fetal diagnosis of Ehlers-Danlos Syndrome
Key exclusion criteria (1 listed)
- Any condition unrelated to Ehlers-Danlos Syndrome
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
Natural History and Epidemiology in terms of clinical, genetic and functional evaluation
Time frame: 25 years
To maintain an established registry in order to assess epidemiology and natural history. Collection of: 1. physical examinations data: assessment of type of the disease (according to Orphanet types) 2. orthopedic and functional data: stature (cm), weight (kg), Beighton score, pain score (numeric scale), presence cardiac lesion (ultrasound) 3. surgical procedures: type, number and site of surgeries disease-related and age at surgeries 4. genetics background: target gene, type of mutation, type of variant detected, clinical significance 5. family history: inheritance in maternal or paternal line 6. treatment information: pharmacological, devices, supplements, and other treatments Clinical, orthopedic, surgical, treatment and functional features are updated at each follow up. Clinical reports, medical charts, genetic report and imaging are the primary sources of data.
1 secondary outcome
Genotype-Phenotype Correlation among clinical features and molecular background
Time frame: 25 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 5 Nov 2026.
- Background: PubMed 31600821Ritelli M, Rovati C, Venturini M, Chiarelli N, Cinquina V, Castori M, Colombi M. Application of the 2017 criteria for vascular Ehlers-Danlos syndrome in 50 patients ascertained according to the Villefranche nosology. Clin Genet. 2020 Feb;97(2):287-295. doi: 10.1111/cge.13653. Epub 2019 Nov 3.
- Background: PubMed 31533917Ghali N, Sobey G, Burrows N. Ehlers-Danlos syndromes. BMJ. 2019 Sep 18;366:l4966. doi: 10.1136/bmj.l4966. No abstract available.
- Background: PubMed 7378285Black CM, Gathercole LJ, Bailey AJ, Beighton P. The Ehlers-Danlos syndrome: an analysis of the structure of the collagen fibres of the skin. Br J Dermatol. 1980 Jan;102(1):85-96. doi: 10.1111/j.1365-2133.1980.tb05675.x.
- Background: PubMed 5432600Beighton P. Ehlers-Danlos syndrome. Ann Rheum Dis. 1970 May;29(3):332-3. doi: 10.1136/ard.29.3.332. No abstract available.
- Background: PubMed 31562935Benistan K, Gillas F. Pain in Ehlers-Danlos syndromes. Joint Bone Spine. 2020 May;87(3):199-201. doi: 10.1016/j.jbspin.2019.09.011. Epub 2019 Sep 25. No abstract available.
- Background: PubMed 31432500Hausser I. Diagnosis of Ehlers-Danlos syndrome: data deficiency still does not allow establishment of a complete history of the disease and its pathomechanisms. Br J Dermatol. 2020 Mar;182(3):535-536. doi: 10.1111/bjd.18373. Epub 2019 Aug 20. No abstract available.
- Background: PubMed 31329366Jesudas R, Chaudhury A, Laukaitis CM. An update on the new classification of Ehlers-Danlos syndrome and review of the causes of bleeding in this population. Haemophilia. 2019 Jul;25(4):558-566. doi: 10.1111/hae.13800. Epub 2019 Jun 10.
- Background: PubMed 31287330De Baets S, Calders P, Verhoost L, Coussens M, Dewandele I, Malfait F, Vanderstraeten G, Van Hove G, Van de Velde D. Patient perspectives on employment participation in the "hypermobile Ehlers-Danlos syndrome". Disabil Rehabil. 2021 Mar;43(5):668-677. doi: 10.1080/09638288.2019.1636316. Epub 2019 Jul 9.
- Background: PubMed 30783660Copetti M, Morlino S, Colombi M, Grammatico P, Fontana A, Castori M. Severity classes in adults with hypermobile Ehlers-Danlos syndrome/hypermobility spectrum disorders: a pilot study of 105 Italian patients. Rheumatology (Oxford). 2019 Oct 1;58(10):1722-1730. doi: 10.1093/rheumatology/kez029.
- Background: PubMed 30703284Mu W, Muriello M, Clemens JL, Wang Y, Smith CH, Tran PT, Rowe PC, Francomano CA, Kline AD, Bodurtha J. Factors affecting quality of life in children and adolescents with hypermobile Ehlers-Danlos syndrome/hypermobility spectrum disorders. Am J Med Genet A. 2019 Apr;179(4):561-569. doi: 10.1002/ajmg.a.61055. Epub 2019 Jan 31.
- Derived from this study: PubMed 42363793Morri M, Tremosini M, Forni C, Moroni A, Pedrini E, Cecco AD, Gnoli M, Sangiorgi L. Characteristics of Pain in Patients Diagnosed With Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders. An Observational Study. Pain Res Manag. 2026;2026(1):e6664142. doi: 10.1155/prm/6664142.
- Institutional webpage of Registries For Rare Hereditary DiseasesLink provided by the sponsor.
Related trials for Ehlers-Danlos Syndrome
Not yet recruiting
COG+OT Telerehabilitation for Adults With Subjective Cognitive Complaints
Subjective Cognitive Complaints, Ehlers-Danlos Syndrome
RecruitingObservational study
Metabolic Phenotyping in vEDS
Vascular Ehlers-Danlos Syndrome, Vascular Ehlers Danlos Syndrome
Not yet recruitingObservational study
CLINICAL AND BIOLOGICAL DATABASE OF PATIENTS WITH NON-VASCULAR EHLERS-DANLOS SYNDROMES
Ehlers-Danlos Syndromes (EDS)
Not yet recruiting
Evaluation of the Role of Serum Tenascin-X Levels in the Diagnosis of Hypermobile Ehlers-Danlos Syndrome
Ehlers-Danlos Syndromes (EDS)
Enrolling by invitationObservational study
Presentation of Young Adults With and Without Joint Hypermobility
Hypermobile Ehlers-Danlos Syndrome, Postural Orthostatic Tachycardia Syndrome (POTS)
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.
Luca Sangiorgi, MD, PhD, MS principal investigator
Istituto Ortopedico Rizzoli
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 Ehlers-Danlos Syndrome, run by Luca Sangiorgi at 1 site in Italy.
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 1 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: looking for participants now, as of the sponsor's last update on 5 Nov 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 Italy. 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 Marina Mordenti, PhD (+39 05 6366062, registri.malattierare@ior.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Natural History and Epidemiology in terms of clinical, genetic and functional evaluation (time frame: 25 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 NCT04133272, which also lists 11 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 5 Nov 2026.