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

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ClinicalTrials.gov Identifier: NCT03575221
Recruitment Status : Recruiting
First Posted : July 2, 2018
Last Update Posted : July 4, 2022
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )

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:

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 Population:

Individuals previously enrolled in 97-CH-0064, or other NIH OI study protocols from whom childhood data were collected at the NIH. Or individuals from birth to age 12 years at enrollment with a diagnosis of OI type III XVIII and potential additional types to be identified by OI genetic mutations.

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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


Group/Cohort
Enrollees
Individuals with Osteogenesis Imperfecta



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 ]


Information from the National Library of Medicine

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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.


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): NCT03575221


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

Locations
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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
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Principal Investigator: Joan C Marini, M.D. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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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    Key Record Dates
Last Update Posted: July 4, 2022
Last Verified: June 14, 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
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.

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