BBD Longitudinal Study of Osteogenesis Imperfecta

Osteogenesis Imperfecta Clinical Trial

Official title:

Rare Diseases Clinical Research Network Brittle Bone Disease Consortium Longitudinal Study of Osteogenesis Imperfecta

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02432625
• Other study ID #: H36165
• Status: Recruiting
• Start date: June 2015
• Est. completion date: December 2026

Study information

• Verified date: November 2023
• Source: Baylor College of Medicine
• Contact: Dianne Nguyen
• Phone: 713.798.6694
• Email: diannen[@]bcm.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Osteogenesis Imperfecta (OI) is a rare disorder of increased bone fragility characterized by fractures with minimal or absent trauma, dentinogenesis imperfecta (DI), and, in adult years, hearing loss. It is seen in both genders and all races. The clinical features of OI represent a continuum varying from perinatal lethality to individuals with severe skeletal deformities, mobility impairments, and very short stature to nearly asymptomatic individuals with a mild predisposition to fractures, normal stature, and normal lifespan. Fractures can occur in any bone, but are most common in the extremities. These disorders can be devastating and progressive and result in deformity, chronic pain, impaired function and loss of quality of life.

The overall goal of this study is to answer specific question about the natural history of brittle bone diseases as defined by molecular etiology and to develop the foundation for prospective clinical studies.

Description:

The purpose of this natural history study is to perform a long-term follow-up of a large group of people with osteogenesis imperfecta (OI). The research aims are:

1. To collect natural history data on all individuals enrolled in this longitudinal study. The cause of the brittle bone disease will be compared with things like severity, various features and response to treatments.

2. To determine how often people with type I OI have vertebral compression fractures of the spine.

3. To determine how often people with OI develop scoliosis (curvature of the spine).

4. To determine how often people with OI have problems with teeth alignment and how dental health impacts a person's quality of life.

5. To determine the effect of pregnancy in women with OI.

There will be a total of 1000 people with OI in this study. Participants will be asked to come in every year if 17Y and younger or every other year if 18Y and older for a total of five years.

The following information will be collected at the study visits:

Birth History and past surgical history, Current medical history, Scoliosis evaluation, Walking ability Questionnaire, Dental Quality of Life Questionnaire, Scoliosis and fractures Quality of Life Questionnaires, Physical development evaluation, Medications Use

The following tests will be performed:

Physical exam, dental exam, lung function test, hearing test, mobility test.

The following X-rays will be taken:

DEXA scan, X-ray of the spine, X-ray of the jaw.

Biospecimen (urine and blood) samples will be collected.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: December 2026
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Natural History Study:

Inclusion Criteria:

• Individuals with OI diagnosed by molecular (DNA) analysis OR

• Individuals whose clinical history and radiographs are highly suggestive of OI, but whose diagnosis has not been verified by biochemical or molecular studies

Exclusion criteria:

• Individuals who are unable to return for their scheduled follow up visits.

• Individuals with skeletal dysplasias other than OI

• Individuals with OI and a second genetic or syndromic diagnosis

Vertebral Compression Fractures component Inclusion criteria

• Patients with nonsense or frameshift mutations in COL1A1 or COL1A2 of any age and clinical features of OI type I.

Exclusion criteria

• Use of a bone-acting treatment agent such as bisphosphonates, calcitonin, calcitriol, fluoride, etc., within one year of enrollment.

• Conditions other than Osteogenesis Imperfecta-HaploInsufficiency (OI-HI) affecting muscle and/or bone development (i.e. cerebral palsy, rickets)

• Nonsense or frame shift mutations in the final coding exons of COL1A1 or COL1A2, as this may not lead to haploinsufficiency.

Scoliosis in OI component:

Inclusion Criteria

• All study participants between the ages of 3 to 17 years OR

• Study participants 18 years and older with scoliosis

Dental and Craniofacial Abnormalities in OI component:

Inclusion Criteria • All subjects aged 3 years and older enrolled in the Longitudinal Study Exclusion Criteria Subjects who refuse the dental examination

Pregnancy in OI component:

Inclusion criteria

• Females of reproductive age with mutations in any known gene causing OI, who are contemplating pregnancy within 5 years of enrollment in the Natural History Study OR Females who are pregnant with available pre-pregnancy BMD (within 5 years prior to the first pregnancy visit).

Exclusion criteria

• Males

• Females who are peri-menopausal or menopausal

• Females who had gestations associated with higher order multiples.

Related Conditions & MeSH terms

• Osteogenesis Imperfecta

Locations

Country	Name	City	State
Canada	Shriners Hospital for Children	Montreal	Quebec
United States	Kennedy Krieger Institute / Hugo W. Moser Research Institute	Baltimore	Maryland
United States	Baylor College of Medicine	Houston	Texas
United States	University of California Los Angeles	Los Angeles	California
United States	Shriners Hospital for Children, Chicago / Marquette University	Milwaukee	Wisconsin
United States	Hospital for Special Surgery	New York	New York
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Oregon Health and Science University	Portland	Oregon
United States	University of South Florida	Tampa	Florida
United States	Children's National Medical Center	Washington	District of Columbia
United States	AI Dupont Hospital for Children	Wilmington	Delaware

Sponsors (11)

Lead Sponsor	Collaborator
Baylor College of Medicine	Alfred I. duPont Hospital for Children, Children's National Research Institute, Hospital for Special Surgery, New York, Hugo W. Moser Research Institute at Kennedy Krieger, Inc., Oregon Health and Science University, Phoenix Children's Hospital, Shriners Hospitals for Children, University of California, Los Angeles, University of Nebraska, University of South Florida

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Natural History of OI	The molecular basis of the brittle bone disease will be correlated with phenotype, disease progression and response to current standard of care therapies.	5 years
Secondary	Incidence and progression of scoliosis in OI	Incidence and progression of scoliosis in OI analyzed by subtype and Cobb Angle assessment	5 years
Secondary	Number Vertebral compression fractures in OI HaploInsufficiency	Number and location of Vertebral compression fractures in OI-HI	5years
Secondary	Incidence of Oral and craniofacial anomalies	Incidence and progression of oral and craniofacial anomalies as captured by panorex and dental exam	5 years
Secondary	Satisfaction of Oral Health 15Y+	Satisfaction of Oral health as measure by the OHIP 20	5 years
Secondary	Satisfaction of Oral Health 11Y-14Y	Satisfaction of Oral health as measure by the Oral health QOL 11-14Yrs	5 years
Secondary	Effect of pregnancy in women with OI	Change in Spine, Hip, and radius Bone Mineral Density in pregnant women with OI	2 years