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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 : October 28, 2016
Information provided by (Responsible Party):

Study Description
Brief Summary:

Osteogenesis Imperfecta (OI) is a rare disorder that causes bones to break easily. People with OI may have broken bones with little or no trauma, dentinogenesis imperfecta (DI), and, in adult years, hearing loss. It is seen in both genders and all races. OI can range from very severe to very mild. Individuals with the most severe type of OI may die at birth. People with severe OI who survive may have bowed arms and legs, very short stature and be unable to walk. People with the mildest form of OI may only break bones occasionally and have normal height and lifespan. People with OI also often have problems with the spine. The spine problems include compression fractures and scoliosis (a curvature of the spine). DI is characterized by grey or brown teeth that may chip and wear down and break easily.

Before the genetic cause of OI was known, OI was classified into four types. Each type was based upon the symptoms and severity of OI. In most people with OI, the cause is a change in one of the genes that makes a protein called type 1 collagen. In the past decade, it was discovered that in about 5% of people with OI it is in another gene. Some doctors now classify OI both on how severe it is as well as which gene is causing OI.

Our research aims are:

  1. Perform DNA testing and collect natural history data on all individuals enrolled in this longitudinal study. The genetic cause of the brittle bone disease will be compared with things like severity, various features and response to treatments.
  2. We will see how often people with type I OI have vertebral compression fractures of the spine. We will do x-rays to see how often they get compression fractures of the vertebrae, what happens over time and any risk factors that increase the risk of these compression fractures.
  3. We will follow people with all forms of OI to see how often they develop scoliosis (curvature of the spine). We will look at the effects of scoliosis on lung function, ability to walk and quality of life. We will also look at the effects of various treatments (bracing, surgery, etc.) on scoliosis and lung function.
  4. We will look at dental health in people with OI. We will see how often people with OI have problems with teeth alignment. Importantly, we will see how dental health impacts a person's quality of life.

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). We will collect information including:

  • medical history
  • number of broken bones,
  • surgeries done
  • medications taken,
  • ability to walk,
  • pain
  • lung function and breathing
  • hearing
  • bone mineral density The overall goal is to improve the health and quality of life of people with OI.

There will be a total of 1000 people with OI in this study.

We will ask you to come in every year for five years and we will do the following tests or ask you about your:

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 you are using

We will perform a physical exam, a dental exam, assess how well your lungs are working, perform a hearing test, measure your ability to walk and get around, assess your strength and if you are able to do certain things for yourself, perform a Walk Test.

We will take the following X-rays:measure your bone density (strength) with a DEXA scan, take an X-ray of your spine, take an X-ray of your hand, take an X-ray of your jaw.

We will collect the following samples from you:

We will collect 1 teaspoon blood to study your gene, may collect skin cells with a biopsy, and collect 1 teaspoon of blood and 2 teaspoon of urine for future research on OI.

Study Design

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 2020
Estimated Study Completion Date : June 2025

Groups and Cohorts

Outcome Measures

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 assessment of therapeutic interventions

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

  3. Oral and craniofacial anomalies [ Time Frame: 5 years ]
    incidence and progression of oral and craniofacial

Biospecimen Retention:   Samples With DNA
  1. Blood
  2. Skin cells
  3. Urine

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Senior
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.

Inclusion Criteria:

  • Natural History Study:

    • Have had a DNA test or skin collagen test that proves you have OI or
    • Your clinical history and x-rays are highly suggestive of OI, but your diagnosis has not been verified by collagen or DNA testing
  • Vertebral Compression Fractures component

    • You have a genetic change where your body makes half the normal amount of collagen. These types of genetic changes are called nonsense or frameshift mutations in COL1A1 or COL1A2 genes
  • Scoliosis in OI component:

    • You are older than 3 years of age
  • Dental and Craniofacial Abnormalities in OI component:

    • You are older than 3 years of age and agree to a dental exam and to digital photos of teeth and face being taken.

Exclusion Criteria:

  • Natural History Study

    • You are can't return for study visits at least yearly
    • You have a condition other than OI
    • You have OI and a second genetic or syndromic diagnosis
  • Vertebral Compression Fractures component

    • You have used a medication such as bisphosphonates, calcitonin, calcitriol, fluoride, etc., in the past year.
    • You have conditions other than OI that affects muscle and/or bone development (examples include cerebral palsy, rickets, etc.)
    • You have nonsense or frame shift mutations in the final coding exons of COL1A1 or COL1A2.
  • Scoliosis in OI component:

    • You are unable to have spine x-rays taken.
  • Dental and Craniofacial Abnormalities in OI component:

    • You refuse the dental examination.
Contacts and Locations

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

Contact: Dianne Dang 713.798.6694 diannen@bcm.edu

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, District of Columbia
Children's National Medical Center Recruiting
Washington, District of Columbia, United States, 21205
Contact: Marianne Floor    210-320-2157    mfloor@gmail.com   
Principal Investigator: Laura Tosi, MD         
United States, Maryland
Kennedy Krieger Institute / Hugo W. Moser Research Institute Recruiting
Baltimore, Maryland, United States, 21205
Contact: Sheila Lampel, RN, BSN    443-923-9328    Lampel@kennedykrieger.org   
Principal Investigator: Emily Germain-Lee, MD         
United States, Nebraska
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198
Contact: Jennifer Goodwin, B.S.    402-559-0681    Jennifer.goodwin@unmc.edu   
United States, New York
Hospital for Special Surgery Recruiting
New York, New York, United States, 10021
Contact: Sobiah Khan    212-774-2355    KhanS@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 Samad    713-798-2109    Dianne.samad@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 Research Institute
Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
University of California, Los Angeles
Oregon Health and Science University
University of Nebraska
Study Chair: V. Reid Sutton, M.D. Baylor College of Medicine
Study Chair: Frank Rauch, M.D. McGill University
More Information

Responsible Party: Brendan Lee, Professor and Chairman, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT02432625     History of Changes
Other Study ID Numbers: 7701
First Posted: May 4, 2015    Key Record Dates
Last Update Posted: October 28, 2016
Last Verified: October 2016

Keywords provided by Brendan Lee, Baylor College of Medicine:
Osteogenesis Imperfecta
Brittle Bone Disorder
Rare Disease Clinical Research Network

Additional relevant MeSH terms:
Rare Diseases
Osteogenesis Imperfecta
Disease Attributes
Pathologic Processes
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Genetic Diseases, Inborn
Collagen Diseases
Connective Tissue Diseases