Epigenetic Regulation of Osteogenesis Imperfecta Severity : miROI Study

Osteogenesis Imperfecta Clinical Trial

— miROI  

Official title:

Epigenetic Regulation of Osteogenesis Imperfecta Severity : miROI Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04009733
• Other study ID #: 69HCL19_0021
• Secondary ID: 2019-A00521-56
• Status: Completed
• Phase: N/A
• Start date: October 3, 2019
• Est. completion date: April 24, 2022

Study information

• Verified date: May 2023
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: April 24, 2022
• Est. primary completion date: April 24, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Osteogenesis Imperfecta

Intervention

Biological:
• Blood sample
A study specific blood sample will be collected.
• Blood sample
Pre-collected serum of cohort OFELY and MODAM for women, STRAMBO for men will be used for the study.

Locations

Country	Name	City	State
France	Hôpital Edouard Herriot	Lyon

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)