Natural History of the Collagen-Related Disorder Osteogenesis Imperfecta and Genotype Phenotype Correlation

A Natural History of the Collagen-Related Disorder Osteogenesis Imperfecta and the Genotype-Phenotype Correlation

Background:

Osteogenesis Imperfecta (OI) is a connective tissue disorder. OI affects many aspects of a person s health and growth. It can cause frequent fractures, short stature, and bowing of the long bones. There is no known cure for OI so researchers want to learn more about it.

Objectives:

To obtain a natural history of the course of OI. To find changes in genes that affect the disease.

Eligibility:

People from birth to age 12 years with certain types of OI

People who previously had childhood data collected in certain other protocols

Design:

Participants will stay in the clinic for a few days each visit. Visits will be about every 3-4 months to age 5 then about every 6-12 months. Visits may include:

Medical history

Physical exam

Hearing test

Dental exam

Blood, urine, and heart tests

Breathing measured while wearing a clear plastic hood for about 30 minutes

Tests of motion, strength, and motor skills

X-rays of the left hand, chest, legs, and spine

Bone density scan. Participants will lie on a flat table while a very small dose of x-rays is passed through the body.

Computed tomography and magnetic resonance imaging scans. Participants will lie on an exam table that moves in and out a scanner.

Breathing tests using stickers on the chest, a light probe on a finger or foot, and a face mask

Ultrasound of the kidneys, ureters, and bladder

Questionnaires

A small section of skin removed from the arm or thigh

For some tests, participants may take medicine to make them sleepy.

Participants may give separate consent for photos to be taken.

Study Overview

• Status: Completed
• Conditions: Osteogenesis Imperfecta; Short Stature

Detailed Description

study Description:

This is a longitudinal study of the natural history of the collagen-related disorder osteogenesis imperfecta (OI), that includes enrolling new patients under the age of 12 years, along with an extended data collection from adult patients on whom previous childhood data was collected at the NIH.

Objectives:

Primary Objectives: 1) Identify and monitor longitudinal functional outcomes of individuals with collagen and collagen-related disorders, with focuses on identifying underlying contributing factors and comorbidities for scoliosis; gaining insight into occurrence and progression of cardiac valvular abnormalities; pathogenesis of primary lung parenchymal defects; and establish novel data relating to metabolism in OI and its relationship to obesity. 2) Correlate genotypic and phenotypic expression. 3) Identify genetic factors that modify the severity of clinical expression

Secondary Objectives: Adapt and develop standard of care management guidelines for individuals with collagen and collagen-related disorders.

Endpoints:

Primary Endpoints: 1) Clinical course, underlying pathogenesis, and comorbidities in the assessed systems in individuals with OI including for each focus: scoliosis progression across age, scoliosis progression relating to predictive factor, and scoliosis progression relating to mutation spectrum; time to development of valvular abnormality; development of pulmonary tissue abnormalities, presence/absence of pulmonary tissue abnormality, and time to development of pulmonary tissue abnormality; time to development of metabolic abnormality. 2) Correlation of phenotype relating to genotype. 3) Causes of morbidities in individuals with OI.

Secondary endpoints: Tolerability and feasibility of each measure of the clinical battery of assessments based on clinical observation.

• Study Type: Observational
• Enrollment (Actual): 42

Contacts and Locations

• Study Contact: Name: Joan C Marini, M.D.; Phone Number: (301) 594-3418; Email: marinij@cc1.nichd.nih.gov
• Study Contact Backup: Name: Joshua J Zimmerberg, M.D.; Phone Number: (301) 496-6571; Email: zimmerbj@mail.nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Individuals of all ages, races, genders, and nationalities@@@@@@

Description

• INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet either #1 OR #2 of the following criteria:

1. Individuals previously enrolled in 97-CH-0064, or other NIH OI study protocols for whom childhood data were collected at the NIH.

   OR

2. Individuals from birth to age 12 years at enrollment to this protocol 18-CH-0120 with

a diagnosis of any of OI type III - XVIII or potential additional types.

Diagnosis of OI determined by identification of:

1. A mutation in one allele of genes causing autosomal dominant OI types

   (COL1A1, COL1A2, or IFITM5), OR

2. at least one mutation in genes that are indicative of the autosomal recessive OI types.

OR

Individuals with a clinical diagnosis of OI, and a mutation in one of the above genes identified through the Rare Bone disease screening protocol (04-CH-0077).

EXCLUSION CRITERIA:

• Individuals with the diagnosis of OI Type I.
• Individuals who cannot travel to the NIH because of their medical condition.
• Individuals who, in the opinion of the Investigator, are unable to comply with the protocol or have medical conditions that would potentially increase the risk of participation.

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There are no exclusionary criteria related to race or gender for this protocol.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Enrollees; Individuals with Osteogenesis Imperfecta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical course, underlying pathogenesis, and comorbidities in the assessed systems in individuals with OI	clinical course	Ongoing
Correlation of genotype and phenotype	genotype-phenotype correlations	Ongoing
Causes of morbidities in individuals with OI	clinical course	Ongoing

Secondary Outcome Measures

Outcome Measure	Time Frame
Tolerability and feasibility of each measure of the clinical battery of assessments based on clinical observation	Ongoing

Collaborators and Investigators

• Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: Joshua J Zimmerberg, M.D., Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Publications and helpful links

General Publications

• Ballenger KL, Tugarinov N, Talvacchio SK, Knue MM, Dang Do AN, Ahlman MA, Reynolds JC, Yanovski JA, Marini JC. Osteogenesis Imperfecta: The Impact of Genotype and Clinical Phenotype on Adiposity and Resting Energy Expenditure. J Clin Endocrinol Metab. 2022 Jan 1;107(1):67-76. doi: 10.1210/clinem/dgab679. Erratum In: J Clin Endocrinol Metab. 2021 Oct 30;:

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2018
• Primary Completion (Actual): January 30, 2024
• Study Completion (Actual): January 30, 2024

Study Registration Dates

• First Submitted: June 28, 2018
• First Submitted That Met QC Criteria: June 29, 2018
• First Posted (Actual): July 2, 2018

Study Record Updates

• Last Update Posted (Actual): February 2, 2024
• Last Update Submitted That Met QC Criteria: February 1, 2024
• Last Verified: January 29, 2024

More Information

Terms related to this study

• Keywords: Natural History; Osteogenesis Imperfecta; Collagen; Short Stature
• Additional Relevant MeSH Terms: Endocrine System Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Connective Tissue Diseases; Bone Diseases; Bone Diseases, Developmental; Osteochondrodysplasias; Collagen Diseases; Osteogenesis Imperfecta; Dwarfism
• Other Study ID Numbers: 180120; 18-CH-0120

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: .Once primary and secondary endpoints are met to be able to publish/share, we will create a plan to address the IPD sharing as well.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No