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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 9, 2019
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) )

Tracking Information
First Submitted Date June 28, 2018
First Posted Date July 2, 2018
Last Update Posted Date July 9, 2019
Actual Study Start Date July 30, 2018
Estimated Primary Completion Date December 31, 2029   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: May 31, 2019)
  • Clinical course, underlying pathogenesis, and comorbidities in the assessed systems in individuals with OI [ Time Frame: Ongoing ]
    clinical course
  • Correlation of genotype and phenotype [ Time Frame: Ongoing ]
    genotype-phenotype correlations
  • Causes of morbidities in individuals with OI [ Time Frame: Ongoing ]
    clinical course
Original Primary Outcome Measures
 (submitted: June 29, 2018)
  • Clinical course, underlying pathogenesis, and comorbidities in the assessed systems in individuals with OI [ Time Frame: Ongoing ]
  • Correlation of genotype and phenotype [ Time Frame: Ongoing ]
  • Causes of morbidities in individuals with OI [ Time Frame: Ongoing ]
Change History Complete list of historical versions of study NCT03575221 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: June 29, 2018)
Tolerability and feasibility of each measure of the clinical battery of assessments based on clinical observation [ Time Frame: Ongoing ]
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Natural History of the Collagen-Related Disorder Osteogenesis Imperfecta and Genotype Phenotype Correlation
Official Title A Natural History of the Collagen-Related Disorder Osteogenesis Imperfecta and the Genotype-Phenotype Correlation
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.

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 phenotypic disease 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 Type Observational
Study Design Observational Model: Cohort
Time Perspective: Other
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population Individuals of all ages, races, genders, and nationalities@@@@@@
Condition
  • Osteogenesis Imperfecta
  • Short Stature
Intervention Not Provided
Study Groups/Cohorts Enrollees
Individuals with Osteogenesis Imperfecta
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: June 29, 2018)
125
Original Estimated Enrollment Same as current
Estimated Study Completion Date December 31, 2029
Estimated Primary Completion Date December 31, 2029   (Final data collection date for primary outcome measure)
Eligibility Criteria
  • INCLUSION CRITERIA:
  • Individuals previously enrolled in 97-CH-0064, or other NIH OI study protocols for whom childhood data were collected at the NIH.
  • Individuals from birth to age 12 years at enrollment with a diagnosis of OI type III - XVIII and 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 screening protocol.

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.

<TAB>

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

Sex/Gender
Sexes Eligible for Study: All
Ages up to 100 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Joan C Marini, M.D. (301) 594-3418 marinij@mail.nih.gov
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT03575221
Other Study ID Numbers 180120
18-CH-0120
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )
Study Sponsor Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborators Not Provided
Investigators
Principal Investigator: Joan C Marini, M.D. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date June 27, 2019