Epigenetic Regulation of Osteogenesis Imperfecta Severity : miROI Study

Study Overview
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Brief Summary
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Osteogenesis Imperfecta (OI) is a heterogeneous group of rare connective tissue hereditary diseases responsible for fragility and bone deformity. OI is caused by an autosomal dominant mutation of COL1A1 or COL1A2, encoding α1 and α2 of the collagen, regardless of their phenotypic severity (1 to 5 OI type). This observation suggests the existence of a undetermined mechanism that may be found in epigenetic regulation, including particularly micro Ribonucleic Acids (miRs). Indeed, these small non-coding miRs are involved in the regulation of major steps of cellular processes in different pathologies, especially in bone disease. Currently, no study can provide a satisfactory answer. This is an etiologic study to reveal the correlation between micro-RNAs (miR) expression and the type I or III of the Osteogenesis Imperfecta (OI). The aim of this study is therefore to identify miRs significantly associated with the severity of OI.

Official Title
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Epigenetic Regulation of Osteogenesis Imperfecta Severity : miROI Study

Conditions
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Osteogenesis Imperfecta

Intervention / Treatment
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* Biological: Blood sample
* Biological: Blood sample


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Control population: Male or female 18 years old and over Be part of cohorts STRAMBO, OFELY or MODAM Patients with OI: Male or female ≥18 years old Have COL1A1 or COL1A2 mutation Have a diagnosis of type 1 or 3 from Silence classification made by a rheumatologist expert in bone pathologies Exclusion Criteria: Refusal to participate in the study Have received glucocorticoid treatment for more than 3 months Have received anti-osteoporotic treatment for less than 1 year ago Have Chronic inflammatory rheumatism Have an uncontrolled hypo/hyper thyroidism ou hypo/hyper parathyroidism Have cancer or bone metastases (current or in the past two years) Have benign bone tumors or Paget's disease Have malabsorptive disease (Celiac disease, Whipple's disease, intestinal bypass, short bowel syndrome) and inflammatory bowel disease Pregnant or lactating women Have psychiatric disorders seriously hindering understanding Have difficulties in oral understanding of French language Not a beneficiary of french social security Patients protected by law

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Osteogenesis imperfecta type 1<br>Patients with OI type 1 | Biological: Blood sample<br>* A study specific blood sample will be collected.<br>|
| Experimental: Osteogenesis imperfecta type 3<br>Patients with OI type 3 | Biological: Blood sample<br>* A study specific blood sample will be collected.<br>|
| Active Comparator: Control population<br>The control population corresponds to a pre-existing serum collection of osteoarthritis cohorts (OFELY and MODAM for women, STRAMBO for men). | Biological: Blood sample<br>* Pre-collected serum of cohort OFELY and MODAM for women, STRAMBO for men will be used for the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| micro Ribonucleic Acids (miRs) expression in serum of the patients Osteogenesis imperfecta (OI) type I or III versus control population | Identification of specific miRs expressed in the serum of OI patients using NGS (Next Generation Sequencing). | up to 1 month (after inclusion) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nature of micro Ribonucleic Acids (miRs) identified by Next-Gen Sequencing (NGS ) | Compare the nature of the miRs identified by NGS (Next Generation Sequencing) in serum between the 3 groups of subjects: type 1 Osteogenesis Imperfecta (OI), type 3 OI and controls (controls are patients with osteoarthritis). | Up to 1 month (after inclusion) | 
| Level of expression of micro Ribonucleic Acids (miRs) identified by Next-Gen Sequencing (NGS ) | The objective is to validate expression of miRs identified by NGS (Next Generation Sequencing) in blood samples of patients from 3 groups: an Osteogenesis imperfecta (OI) type 1 cohort and an OI type 3 cohort, recruited for the study, and a pre-existing group of control patients (issued from cohorts OFELY and MODAM for women, STRAMBO for men). Expression of the significant miRs identified by NGS will be measured by Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) and then these results will be compared with same analysis on blood samples of control patients. | Up to 1 month (after inclusion) | 
| Presence of fracture | Severity of OI will be evaluated using radiological data (fracture) extracted from patients' medical records. Association between expression of miRs in patients with OI with the severity of the disease will be studied by statistical analysis. | Up to 1 month (after inclusion) | 
| Presence of biochemical markers of bone turnover in blood | Severity of OI will be evaluated using biological data (biochemical markers of bone turnover) extracted from patients' medical records. Association between expression of miRs in patients with OI with the severity of the disease will be studied by statistical analysis. | Up to 1 month (after inclusion) | 
| Bone pain | Severity of OI will be evaluated using clinical data (bone pain mesured on Visual Analogue Scale) extracted from patients' medical records. Association between expression of miRs in patients with OI with the severity of the disease will be studied by statistical analysis. | Up to 1 month (after inclusion) | 
| Quality of life | Investigators will use a specific questionnaire completed by a rheumatologist at inclusion to obtain more information about a patient's lifestyle. The higher the score the more severe the disease impact and vice versa. Association between expression of miRs in patients with OI with the severity of the disease will be studied by statistical analysis. | Up to 1 month (after inclusion) | 
| Assessment of environmental factors | The investigating team will use information extracted from patients' medical records to obtain environmental information, which includes using a specific questionnaire completed by a rheumatologist with patients at inclusion. Association between expression of miRs in patients with OI with the environmental data will be studied by statistics analysis. | Up to 1 month (after inclusion) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteogenesis imperfecta, micro Ribonucleic acids, epigenetics