Clinical trial NCT04115774: Registry of Osteogenesis Imperfecta
Official title: Registry of Osteogenesis Imperfecta That Collects Clinical, Functional, Genetic, Genealogical, Imaging, Surgical, Quality of Life Data. Data Are Linked to Patients Biological Sample
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Osteogenesis Imperfecta
Keywords: Disease Registry
Natural History Study
Genotype-Phenotype Correlation
Brittle Bone Disease
Lead sponsor: Istituto Ortopedico Rizzoli
Sponsor class: OTHER
First posted: 2019-10-04
Enrollment: 5000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: OTHER
Sampling method: PROBABILITY_SAMPLE
Study population: Patients affected by Osteogenesis Imperfecta. The Registry will include also data on foetuses (prenatal and abortion).

Brief summary: ROI is a retrospective and prospective registry, finalized to care and research. 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 individuated in order to corroborate and integrate data from different resources and aspects of the diseases and to correlate genetic background and phenotypic outcomes, in order to better investigate diseases pathophysiology.

Detailed description: The common way to collect patient information is frequently chaotic and inconvenient (sometimes even unsafe), particularly when dealing with rare diseases. The need to simplify the diagnostic process and to overcome the difficulties of data storage and analysis, suggested in 2013 to implement the Registry of Osteogenesis Imperfecta (ROI).

The ROI relies on an IT Platform named Genotype-phenotype Data Integration platform -GeDI.This solution, realized by a collaboration among Medical Genetic Department and a local software-house (NSI - Nier IT Solution), is a General Data Protection Regulation (GDPR)-compliant, multi-client, web-accessible system and it has been designed according to current medical informatics standards (Orphanet code, ICD-10, Human Genome Variants Society, Findability Accessibility Interoperability Reusability Principles). GeDI is continuously implemented to improve management of persons with Osteogenesis Imperfecta and to help researchers in analysing collected information. ROI is articulated in main sections:

1. Personal data: it comprises general information, birth details and residence data
2. Patient data: including the patients internal code, the hospital code and other details on patients
3. Diagnosis: the diagnosis, the status (affected, suspect, etc.), age at diagnosis, comorbidities, allergies, etc.
4. Genogram: a tool to design family transmission of the disease, flanked by info on diseases status of all included relatives
5. Clinical events: records 23 signs and symptoms of Osteogenesis Imperfecta (representing the main Osteogenesis Imperfecta features) and 12 additional items to describe the disease
6. Genetic Analysis and Alteration: including technique, sample information, duration of analysis, etc. In addition, this section comprises detailed information on detected pathological variants (gene, international reference, DNA change, Protein change, genomic position, etc.)
7. Visits: it includes the typology of the visit (genetic, orthopaedic, rehabilitation, paediatric, etc.), the date of the visit, treatment, prescription, imaging, etc.
8. Surgeries: this section contains information on the surgeries type, the age of the patients, the site/localization of the procedures, etc.
9. Documents: this repository is allowed to store all type of documents (radiological reports, imaging, consents, clinical reports, etc.)
10. Consents: this section comprises a complete overview of all collected consents, including the date of collection.
11. Samples: it comprises the type of samples (DNA, tissue, whole peripheral blood, etc.)

Eligibility criteria: Inclusion Criteria:

* All Osteogenesis Imperfecta patients, including prenatal and fetal diagnosis of Osteogenesis Imperfecta

Exclusion Criteria:

* Any condition unrelated to Osteogenesis Imperfecta

Primary outcomes:
measure: Natural History and Epidemiology
timeFrame: 25 years
Secondary outcomes:
measure: Genotype-Phenotype Correlation
timeFrame: 25 years
Other outcomes:
measure: Disease evolution
timeFrame: 25 years
Locations:
city: Bologna
country: Italy
facility: Irccs Istituto Ortopedico Rizzoli
state: Emilia Romagna
Study officials:
affiliation: Istituto Ortopedico Rizzoli
name: Luca Sangiorgi, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ablin DS, Sane SM. Non-accidental injury: confusion with temporary brittle bone disease and mild osteogenesis imperfecta. Pediatr Radiol. 1997 Feb;27(2):111-3. doi: 10.1007/s002470050079.
citation: Davie MW, Haddaway MJ. Bone mineral content and density in healthy subjects and in osteogenesis imperfecta. Arch Dis Child. 1994 Apr;70(4):331-4. doi: 10.1136/adc.70.4.331.
citation: Chapman S, Hall CM. Non-accidental injury or brittle bones. Pediatr Radiol. 1997 Feb;27(2):106-10. doi: 10.1007/s002470050078.
citation: Lindert U, Cabral WA, Ausavarat S, Tongkobpetch S, Ludin K, Barnes AM, Yeetong P, Weis M, Krabichler B, Srichomthong C, Makareeva EN, Janecke AR, Leikin S, Rothlisberger B, Rohrbach M, Kennerknecht I, Eyre DR, Suphapeetiporn K, Giunta C, Marini JC, Shotelersuk V. MBTPS2 mutations cause defective regulated intramembrane proteolysis in X-linked osteogenesis imperfecta. Nat Commun. 2016 Jul 6;7:11920. doi: 10.1038/ncomms11920.
citation: Martin E, Shapiro JR. Osteogenesis imperfecta:epidemiology and pathophysiology. Curr Osteoporos Rep. 2007 Sep;5(3):91-7. doi: 10.1007/s11914-007-0023-z.
citation: Miller ME, Hangartner TN. Temporary brittle bone disease: association with decreased fetal movement and osteopenia. Calcif Tissue Int. 1999 Feb;64(2):137-43. doi: 10.1007/s002239900592.
citation: Moore MS, Minch CM, Kruse RW, Harcke HT, Jacobson L, Taylor A. The role of dual energy x-ray absorptiometry in aiding the diagnosis of pediatric osteogenesis imperfecta. Am J Orthop (Belle Mead NJ). 1998 Dec;27(12):797-801.
citation: Roughley PJ, Rauch F, Glorieux FH. Osteogenesis imperfecta--clinical and molecular diversity. Eur Cell Mater. 2003 Jun 30;5:41-7; discussion 47. doi: 10.22203/ecm.v005a04.
citation: Sillence DO, Senn A, Danks DM. Genetic heterogeneity in osteogenesis imperfecta. J Med Genet. 1979 Apr;16(2):101-16. doi: 10.1136/jmg.16.2.101.
citation: Maioli M, Gnoli M, Boarini M, Tremosini M, Zambrano A, Pedrini E, Mordenti M, Corsini S, D'Eufemia P, Versacci P, Celli M, Sangiorgi L. Genotype-phenotype correlation study in 364 osteogenesis imperfecta Italian patients. Eur J Hum Genet. 2019 Jul;27(7):1090-1100. doi: 10.1038/s41431-019-0373-x. Epub 2019 Mar 18.
citation: Zionts LE, Nash JP, Rude R, Ross T, Stott NS. Bone mineral density in children with mild osteogenesis imperfecta. J Bone Joint Surg Br. 1995 Jan;77(1):143-7.
citation: Hill CL, Baird WO, Walters SJ. Quality of life in children and adolescents with Osteogenesis Imperfecta: a qualitative interview based study. Health Qual Life Outcomes. 2014 Apr 16;12:54. doi: 10.1186/1477-7525-12-54.
citation: Hald JD, Folkestad L, Harslof T, Brixen K, Langdahl B. Health-Related Quality of Life in Adults with Osteogenesis Imperfecta. Calcif Tissue Int. 2017 Nov;101(5):473-478. doi: 10.1007/s00223-017-0301-4. Epub 2017 Jul 4.
citation: Vanz AP, van de Sande Lee J, Pinheiro B, Zambrano M, Brizola E, da Rocha NS, Schwartz IVD, de Souza Pires MM, Felix TM. Health-related quality of life of children and adolescents with osteogenesis imperfecta: a cross-sectional study using PedsQL. BMC Pediatr. 2018 Mar 2;18(1):95. doi: 10.1186/s12887-018-1077-z.