Urinary Biomarkers of OI Pathobiology

Cross-Linked Collagen Peptides as a Urinary Biomarker of OI Pathobiology

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.

Study Overview

• Status: Active, not recruiting
• Conditions: 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 Type: Observational
• Enrollment (Actual): 25

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3G 1A6
      • Shriners Hospital for Children
• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University Of Nebraska Medical Center
  • New York
    • New York, New York, United States, 10021
      • Hospital for Special Surgery
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health Science University
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53201
      • Shriners Hospital for Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Individuals with OI

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HP/LP Ratio	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).	5 Years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HP/LP ratio	The endpoint would be the HP/LP ratio in those with dominant negative type I collagen mutations vs. those with mutations in P3H complex.	5 Years

Collaborators and Investigators

• Sponsor: Baylor College of Medicine
• Collaborators: University of Washington; Shriners Hospitals for Children; University of Nebraska
• 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

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (ACTUAL): January 1, 2021
• Study Completion (ANTICIPATED): December 1, 2025

Study Registration Dates

• First Submitted: August 20, 2015
• First Submitted That Met QC Criteria: August 21, 2015
• First Posted (ESTIMATE): August 24, 2015

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: February 6, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Musculoskeletal Diseases; Connective Tissue Diseases; Bone Diseases; Bone Diseases, Developmental; Osteochondrodysplasias; Collagen Diseases; Osteogenesis Imperfecta
• Other Study ID Numbers: 37358

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO