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Urinary Biomarkers of OI Pathobiology

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ClinicalTrials.gov Identifier: NCT02531087
Recruitment Status : Recruiting
First Posted : August 24, 2015
Last Update Posted : October 28, 2016
Sponsor:
Collaborators:
Information provided by (Responsible Party):

Study Description
Brief Summary:
Osteogenesis imperfecta (OI) is a rare inherited disorder that causes bones to break easily. Individuals with osteogenesis imperfecta break bones often and may have other problems, including hearing loss, dental problems, pain and difficulty getting around. 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. Some doctors now classify OI both on how severe it is as well as which gene is causing OI. When people classify OI this way, there are more than 10 types of OI. The current laboratory testing to determine OI subtype involves the collection of blood and/or skin cells.

Condition or disease
Osteogenesis Imperfecta

Detailed Description:

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. Breaks can occur in any bone, but are most common in the arms and legs. 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. In addition to weak teeth, the teeth in the upper jaw may not match up with the teeth in the lower jaw.

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. When people classify OI this way, there are more than 10 types of OI. The current laboratory testing to determine OI subtype involves the collection of blood and/or skin cells.


Study Design

Study Type : Observational
Estimated Enrollment : 30 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Cross-Linked Collagen Peptides as a Urinary Biomarker of OI Pathobiology
Study Start Date : September 2015
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : September 2025


Groups and Cohorts

Group/Cohort
Individuals with OI
Individuals with OI with confirmed specific genetic mutations
Controls/Unaffected
Individuals who do not have OI and who are not related to an individual with OI


Outcome Measures

Primary Outcome Measures :
  1. HP/LP Ratio [ Time Frame: 5 Years ]
    The endpoint will be to compare the HP/LP ratio in OI patients with collagen overmodification (dominant negative mutations in COL1A1, COL1A2, and biallelic mutations in CRTAP, LEPRE1, PPIB) to those without overmodification (FKBP10, SERPINH1, IFITM5, SERPINF1, WNT1, and haploinsufficient mutations in COL1A1 and COL1A2).


Secondary Outcome Measures :
  1. HP/LP ratio [ Time Frame: 5 Years ]
    The endpoint would be the HP/LP ratio in those with dominant negative type I collagen mutations vs. those with mutations in P3H complex.


Biospecimen Retention:   Samples Without DNA
Urine samples will be collected

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:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Individuals with OI
Criteria

Inclusion Criteria:

  • To be able to participate, you must:

Be enrolled in The Longitudinal Study of OI (NTC #02432625) and have one of the following genetic mutations:

  • glycine substitution mutations in COL1A1 or COL1A2
  • haploinsufficient mutation in COL1A1 or COL1A2
  • mutations in CRTAP, PPIB, or LEPRE1
  • mutations in FKBP10 or SERPINH1
  • mutations in (SERPINF1, WNT1, or IFITM5)
  • dominant negative glycine substitutions and haploinsufficient mutations in COL1A1, and COL1A2

If you are serving as a control, you must not be related to an individual with OI.

Exclusion Criteria:

  • You cannot participate if:
  • You are unable to comply with the sample collection schedule.
  • You are related to one of the OI subjects and would like to serve as a control subject.
  • You have vertebral instrumentation or spinal deformities where we cannot assess lumbar spine aBMD.
  • You have a history of recent fracture (< 3 months).
  • You have serum creatinine above 1x upper limits of normal.
  • You have abnormal kidney function.
  • You are using Minoxidil.
  • You are unable to provide a urine sample readily.
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): NCT02531087


Contacts
Contact: Dianne Dang 713-798-6694 diannen@bcm.edu

Locations
United States, California
University of California Los Angeles Recruiting
Los Angeles, California, United States, 90095
Contact: Samantha Elon    310-794-6420    SAlon@mednet.ucla.edu   
Principal Investigator: Deborah Krakow, M.D.         
United States, Nebraska
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198
Contact: Jennifer Goodwin    402-559-0681    Jennifer.goodwin@unmc.edu   
Principal Investigator: Eric Rush, MD         
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 Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Melanie Abrahamson    503-494-0225    abrahamm@ohsu.edu   
Principal Investigator: Eric Orwoll, M.D.         
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 Recruiting
Milwauke, Wisconsin, United States, 53201
Contact: Angela Caudill    773-385-5868    acaudil@shrinenet.org   
Principal Investigator: Peter Smith, MD         
Canada, Quebec
Shriners Hospital for Children Not yet 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
University of Nebraska
University of Washington
Investigators
Principal Investigator: Vernon Reid Sutton, M.D. Baylor College of Medicine
Principal Investigator: Frank Rauch, M.D. Shriners Hospital for Children
Principal Investigator: David Eyre, Ph.D. University of Washington
More Information

Responsible Party: Brendan Lee, Professor and Chairman, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT02531087     History of Changes
Other Study ID Numbers: 7703
First Posted: August 24, 2015    Key Record Dates
Last Update Posted: October 28, 2016
Last Verified: October 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Osteogenesis Imperfecta
Osteochondrodysplasias
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Genetic Diseases, Inborn
Collagen Diseases
Connective Tissue Diseases