Clinical trial NCT02432625: BBD Longitudinal Study of Osteogenesis Imperfecta
Official title: Rare Diseases Clinical Research Network Brittle Bone Disease Consortium Longitudinal Study of Osteogenesis Imperfecta
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Osteogenesis Imperfecta
Keywords: Osteogenesis Imperfecta
Collagen
Brittle Bone Disorder
Rare Disease Clinical Research Network
COL1A2
Lead sponsor: Baylor College of Medicine
Sponsor class: OTHER
Collaborators: name: Shriners Hospitals for Children
name: Hospital for Special Surgery, New York
name: Children's National Research Institute
name: Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
name: University of California, Los Angeles
name: Oregon Health and Science University
name: University of Nebraska
name: Alfred I. duPont Hospital for Children
name: University of South Florida
name: Phoenix Children's Hospital
name: Marquette University
First posted: 2015-05-04
Enrollment: 1000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Individuals with a diagnosis of Osteogenesis Imperfecta are eligible to enroll in the natural history study.

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Natural History of OI
timeFrame: 10 years
Secondary outcomes:
measure: Incidence and progression of scoliosis in OI
timeFrame: 10 years
measure: Number Vertebral compression fractures in OI HaploInsufficiency
timeFrame: 10 years
measure: Incidence of Oral and craniofacial anomalies
timeFrame: 10 years
measure: Satisfaction of Oral Health 15Y+
timeFrame: 10 years
measure: Satisfaction of Oral Health 11Y-14Y
timeFrame: 10 years
measure: Effect of pregnancy in women with OI
timeFrame: 10 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: Wilmington
country: United States
facility: AI Dupont Hospital for Children
state: Delaware
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Baltimore
country: United States
facility: Kennedy Krieger Institute / Hugo W. Moser Research Institute
state: Maryland
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Milwaukee
country: United States
facility: Shriners Hospital for Children, Chicago / Marquette University
state: Wisconsin
city: Montreal
country: Canada
facility: Shriners Hospital for Children
state: Quebec
Study officials:
affiliation: Baylor College of Medicine
name: V. Reid Sutton, M.D.
role: STUDY_CHAIR
affiliation: McGill University
name: Frank Rauch, M.D.
role: STUDY_CHAIR
References: