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BBD Longitudinal Study of Osteogenesis Imperfecta

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ClinicalTrials.gov Identifier: NCT02432625
Recruitment Status : Recruiting
First Posted : May 4, 2015
Last Update Posted : January 24, 2022
Sponsor:
Collaborators:
Shriners Hospitals for Children
Hospital for Special Surgery, New York
Children's National Research Institute
Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
University of California, Los Angeles
Oregon Health and Science University
University of Nebraska
Children's Mercy Hospital Kansas City
Information provided by (Responsible Party):
Brendan Lee, Baylor College of Medicine

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.


Condition or disease
Osteogenesis Imperfecta

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.

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Study Type : Observational
Estimated Enrollment : 1000 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Rare Diseases Clinical Research Network Brittle Bone Disease Consortium Longitudinal Study of Osteogenesis Imperfecta
Study Start Date : June 2015
Estimated Primary Completion Date : June 2025
Estimated Study Completion Date : December 2026





Primary Outcome Measures :
  1. Natural History of OI [ Time Frame: 5 years ]
    The molecular basis of the brittle bone disease will be correlated with phenotype, disease progression and response to current standard of care therapies.


Secondary Outcome Measures :
  1. Incidence and progression of scoliosis in OI [ Time Frame: 5 years ]
    Incidence and progression of scoliosis in OI analyzed by subtype and Cobb Angle assessment

  2. Number Vertebral compression fractures in OI HaploInsufficiency [ Time Frame: 5years ]
    Number and location of Vertebral compression fractures in OI-HI

  3. Incidence of Oral and craniofacial anomalies [ Time Frame: 5 years ]
    Incidence and progression of oral and craniofacial anomalies as captured by panorex and dental exam

  4. Satisfaction of Oral Health 15Y+ [ Time Frame: 5 years ]
    Satisfaction of Oral health as measure by the OHIP 20

  5. Satisfaction of Oral Health 11Y-14Y [ Time Frame: 5 years ]
    Satisfaction of Oral health as measure by the Oral health QOL 11-14Yrs

  6. Effect of pregnancy in women with OI [ Time Frame: 2 years ]
    Change in Spine, Hip, and radius Bone Mineral Density in pregnant women with OI


Biospecimen Retention:   Samples With DNA
  1. Blood
  2. Urine


Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Individuals with a diagnosis of Osteogenesis Imperfecta are eligible to enroll in the natural history study.
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02432625


Contacts
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Contact: Dianne Nguyen 713.798.6694 diannen@bcm.edu

Locations
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United States, California
University of California Los Angeles Recruiting
Los Angeles, California, United States, 90095
Contact: Samantha Alon    310-794-6420    SAlon@mednet.ucla.edu   
Principal Investigator: Deborah Krakow, MD         
United States, Delaware
AI Dupont Hospital for Children Recruiting
Wilmington, Delaware, United States, 19803
Contact: Cassondra Brown    302-298-7930    Cassondra.Brown@nemours.org   
Principal Investigator: Michael Bober, MD         
United States, District of Columbia
Children's National Medical Center Recruiting
Washington, District of Columbia, United States, 21205
Contact: Austin Austin       ausgillies@gmail.com   
Contact: Gillies         
Principal Investigator: Laura Tosi, MD         
United States, Florida
Tampa Shriners Hospital for Children Recruiting
Tampa, Florida, United States, 33612
Contact: Margaret Gross-King    813-972-2250 ext 7538    mgking@shrinenet.org   
Principal Investigator: Danielle Gomez, MD         
United States, Maryland
Kennedy Krieger Institute / Hugo W. Moser Research Institute Recruiting
Baltimore, Maryland, United States, 21205
Contact: Jennifer Nagy, RN, BSN    443-923-2704    Nagy@kennedykrieger.org   
Principal Investigator: Mahim Jain, MD         
United States, Missouri
Children's Mercy Hospital Recruiting
Kansas City, Missouri, United States, 64108
Contact: Kemi Lewis    816-302-8419    kjlewis@cmh.edu   
Principal Investigator: Eric Rush, MD         
United States, Nebraska
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198
Contact: Elizabeth Strudthoff, B.S.    402-559-0681    elizabeth.strudthoff@unmc.edu   
Principal Investigator: Paul Esposito, MD         
United States, New York
Hospital for Special Surgery Recruiting
New York, New York, United States, 10021
Contact: Holly Loturco    212-774-2355    loturcoh@HSS.EDU   
Principal Investigator: Cathleen Raggio, MD         
United States, Oregon
Oregon Health and Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Catherine Pederson    503-494-0225    pedersec@ohsu.edu   
Principal Investigator: Eric Orwoll, MD         
United States, Texas
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Dianne Nguyen    713-798-6694    diannen@bcm.edu   
Principal Investigator: V.Reid Sutton, MD         
United States, Wisconsin
Shriners Hospital for Children, Chicago / Marquette University Recruiting
Milwaukee, Wisconsin, United States, 53201
Contact: Angela Caudill, MPT    773-385-5868    acaudill@shrinenet.org   
Principal Investigator: Peter Smith, MD         
Canada, Quebec
Shriners Hospital for Children Recruiting
Montreal, Quebec, Canada, H3G 1A6
Contact: Michaela Durigova    514-282-7158    mdurigova@shriners.mcgill.ca   
Principal Investigator: Frank Rauch, MD         
Sub-Investigator: Francis Glorieux, MD         
Sponsors and Collaborators
Baylor College of Medicine
Shriners Hospitals for Children
Hospital for Special Surgery, New York
Children's National Research Institute
Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
University of California, Los Angeles
Oregon Health and Science University
University of Nebraska
Children's Mercy Hospital Kansas City
Investigators
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Study Chair: V. Reid Sutton, M.D. Baylor College of Medicine
Study Chair: Frank Rauch, M.D. McGill University
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Responsible Party: Brendan Lee, Professor and Chairman, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT02432625    
Other Study ID Numbers: H36165
First Posted: May 4, 2015    Key Record Dates
Last Update Posted: January 24, 2022
Last Verified: January 2022
Keywords provided by Brendan Lee, Baylor College of Medicine:
Osteogenesis Imperfecta
Collagen
Brittle Bone Disorder
Rare Disease Clinical Research Network
COL1A2
Additional relevant MeSH terms:
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Osteogenesis Imperfecta
Osteochondrodysplasias
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Genetic Diseases, Inborn
Collagen Diseases
Connective Tissue Diseases