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

• ClinicalTrials.gov Identifier: NCT03575221
• Recruitment Status: Recruiting
• First Posted: July 2, 2018
• Last Update Posted: December 16, 2021
• Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )

Study Description

Brief Summary:

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.

Condition or disease
Osteogenesis Imperfecta; Short Stature

Detailed Description:

We propose a longitudinal study of the natural history of the collagen-related disorder osteogenesis imperfecta (OI). The overall objectives are to 1) obtain a comprehensive assessment of the natural history and progression of the multiple secondary features of osteogenesis imperfecta, and 2) further the understanding of genotype-phenotype correlation using biosamples collected from well-characterized affected individuals. This study is in part a continuation of protocol 97-CH-0064, and thus will continue to follow individuals with OI enrolled in that protocol, to incorporate biosamples obtained, and to analyze data collected under that protocol. The major objectives of protocol 97-CH-0064 have focused on radiographic features including scoliosis and rib deformities, bone density, intensive rehabilitation, and physical therapy. New developments in genetics, bone tissue biology, and pathophysiology of OI in the past decade, along with the increasing life expectancy of affected individuals, highlight a need for the continuation and expansion of this natural history study to understand the full disease phenotypic spectrum, and to generate biobanks of tissue samples from well-characterized study participants for continued research. This proposed protocol will: 1) Continue to follow study participants, use biosamples, and analyze data gathered under protocol 97-CH-0064 (which will be closed upon the start of this protocol). 2) Expand to include currently known collagen-related OI types V-XVIII and potential additional types, in addition to collagen OI types III and IV included under protocol 97-CH-0064. 3) Extend the age criteria for study participants to include individuals of all ages, with age at study enrollment targeted to those from birth to 12 years. This will allow us to follow clinical outcomes of young adults who had aged out of prior NICHD OI research programs. The major objectives will focus on: 1) Continued comprehensive assessment of radiographic, bone density, audiology, dental, cardiovascular, pulmonary, and neurologic manifestations, and physical rehabilitation. The immediate goals from this will encompass a) identifying underlying contributing factors and comorbidities for scoliosis, b) gaining insight into occurrence and progression of cardiac valvular abnormalities, and c) elucidating the pathogenesis of primary lung parenchymal defects in individuals with OI. 2) Additional comprehensive assessment of endocrine and renal systems. The novel evaluation of metabolism in individuals with OI will allow understanding of obesity prevalence in this population. 3) Continued genetic and molecular biology investigations of OI.

Study Design

• Study Type: Observational
• Estimated Enrollment: 125 participants
• Observational Model: Cohort
• Time Perspective: Other
• Official Title: A Natural History of the Collagen-Related Disorder Osteogenesis Imperfecta and the Genotype-Phenotype Correlation
• Actual Study Start Date: July 30, 2018
• Estimated Primary Completion Date: December 31, 2029
• Estimated Study Completion Date: December 31, 2029

Groups and Cohorts

Group/Cohort
Enrollees; Individuals with Osteogenesis Imperfecta

Outcome Measures

Primary Outcome Measures :

1. Clinical course, underlying pathogenesis, and comorbidities in the assessed systems in individuals with OI [ Time Frame: Ongoing ]
   clinical course
2. Correlation of genotype and phenotype [ Time Frame: Ongoing ]
   genotype-phenotype correlations
3. Causes of morbidities in individuals with OI [ Time Frame: Ongoing ]
   clinical course

Secondary Outcome Measures :

1. Tolerability and feasibility of each measure of the clinical battery of assessments based on clinical observation [ Time Frame: Ongoing ]

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

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

Criteria

• 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.

Contacts and Locations

Contacts

Contact: Joan C Marini, M.D.; (301) 594-3418; marinij@cc1.nichd.nih.gov

Locations

United States, Maryland

National Institutes of Health Clinical Center; Recruiting

Bethesda, Maryland, United States, 20892

Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 prpl@cc.nih.gov

Sponsors and Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Principal Investigator: Joan C Marini, M.D.; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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;:.

• Responsible Party: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• ClinicalTrials.gov Identifier: NCT03575221
• Other Study ID Numbers: 180120; 18-CH-0120
• First Posted: July 2, 2018
• Last Update Posted: December 16, 2021
• Last Verified: September 30, 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) ):

Osteogenesis Imperfecta; Collagen; Short Stature; Natural History

Additional relevant MeSH terms:

Dwarfism; Osteogenesis Imperfecta; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Endocrine System Diseases; Osteochondrodysplasias; Collagen Diseases; Connective Tissue Diseases