Osteogenesis ImperfectaNCT00001594
Evaluation and Intervention for the Effects of Osteogenesis Imperfecta
An observational study of Osteogenesis Imperfecta, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
Trial summary
We propose a longitudinal study of the natural history of types III and IV osteogenesis imperfecta for children age birth to 25 years. A consistent objective throughout this study is to obtain a comprehensive assessment of the natural history and progression of the multiple secondary features of osteogenesis… Read more about this study
- Who is it for?
- Ages Up to 10 years
- Conditions the study is for
- Osteogenesis Imperfecta
- How many people
- 88 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Jan 1997to not given
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 10 years
- All sexes
- No healthy volunteers
- Child
Study population: Children will be recruited from the United States. This recruitment will be accomplished by our contacts with the Osteogenesis Imperfecta Foundation, parent-to-parent communication, and outside referrals from other health care providers
Who may be able to join
- Children will be recruited from the United States. This recruitment will be accomplished by our contacts with the Osteogenesis Imperfecta Foundation, parent-to-parent communication, and outside referrals from other health care providers.
- There are no exclusionary criteria related to race or gender for this protocol.
- Children enrolled in this study will be limited to those with Sillence Types III and IV OI, as determined by clinical and genetic criteria.
- Patients age birth to 10 years at enrollment will be considered for this protocol.
- Children who have not had skin biopsy done for collagen analysis at another facility are preferred for participation in this study. However, previous skin biopsy at another facility will not preclude participation in this protocol.
Who cannot join
- Children who can be expected to attain at least some degree of ambulatory skill or have high potential for achieving independent locomotion with assistive technology.
- Children who are clinically too severe to benefit from this program are defined by the following criteria:
- The ratio of head circumference age (the age for which the child's head or body size falls at the 50th percentile) to body length age (the age for which the child's length falls at the 50th percentile) is 7:1 or greater;
- Children who are 24 months of age, and who are unable to sit unsupported for 60 seconds and are unable to demonstrate the ability to prop themselves on upper extremities in the prone position;
- Children who have other significant medical problems, especially severe cardiopulmonary problems, which have an impact on their physical development.
- Compliance with the visit schedule, maintenance of the physical therapy program, and completion of the measurement tools are central to our analysis of the outcomes of this study. Failure to comply with these conditions will constitute exclusion criteria.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Evaluation and Intervention for Ambulation, Growth, and Basilar Invagination in Osteogenesis Imperfecta
We propose a longitudinal study of the natural history of types III and IV osteogenesis imperfecta for children age birth to 25 years. A consistent objective throughout this study is to obtain a comprehensive assessment of the natural history and progression of the multiple secondary features of osteogenesis imperfecta. In addition to radiographic, bone density, physical rehabilitation and dental manifestations, we will assess the cardiovascular, pulmonary, neurological, and audiology systems.
The major objectives of this protocol focus on rehabilitation and physical therapy studies, pulmonary and cardiovascular function, neurological features, audiological studies and genetic and molecular biology aspects of OI. A major objective in this study is to expand the intensive rehabilitation and physical therapy studies of children with types III and IV OI. This objective continues the work that has been done in the Rehabilitation Department of the Clinical Center for the past 20 years on these patients. However, the focus of this objective is changing to include studies of scoliosis and its effect on function, studies of chest proportions and rib deformities, and studies of nonkinetic variables related to motor performance, such as temperament, competence, coping, and resilience in children with OI. The second major objective is the longitudinal study of pulmonary function in children with types III and IV OI. It is well known that cardiopulmonary complications are a major cause of disability and death in adults with OI; the developmental patterns of these complications, and whether susceptible individuals can be identified in childhood, is unknown. The third major objective of these studies of secondary features is to determine the incidence of basilar invagination and develop a monitoring and management plan for this neurological feature. Next, the prevalence, severity, age of onset and genotypic/phenotypic correlation of hearing loss among children with types II and IV OI remains poorly understood; therefore, the study of audiological features is our fourth major objective. The final major objective in this study is the continued study of the genetic and molecular biology aspect of OI. Patients will have skin biopsies for collagen studies at the biochemical and molecular level. Parents will have blood drawn for determination of mosaic status for the mutation that causes their child s OI. These studies will provide further information on genotype/phenotype correlation and other variables in OI genetics. As appropriate, bone chips from emergency or elective surgical procedures on the participants will be used to study osteoblast function in OI.
Read the detailed description
We propose a longitudinal study of the natural history of types III and IV osteogenesis imperfecta for children age birth to 30 years. A consistent objective throughout this study is to obtain a comprehensive assessment of the natural history and progression of the multiple secondary features of osteogenesis imperfecta. In addition to radiographic, bone density, physical rehabilitation and dental manifestations, we will assess the cardiovascular, pulmonary, neurological, and audiology systems.
The major objectives of this protocol focus on rehabilitation and physical therapy studies, pulmonary and cardiovascular function, neurological features, audiological studies and genetic and molecular biology aspects of OI. A major objective in this study is to expand the intensive rehabilitation and physical therapy studies of children with types III and IV OI. This objective continues the work that has been done in the Rehabilitation Department of the Clinical Center for the past 20 years on these patients. However, the focus of this objective is changing to include studies of scoliosis and its effect on function, studies of chest proportions and rib deformities, and studies of nonkinetic variables related to motor performance, such as temperament, competence, coping, and resilience in children with OI. The second major objective is the longitudinal study of pulmonary function in children with types III and IV OI. It is well known that cardiopulmonary complications are a major cause of disability and death in adults with OI; the developmental patterns of these complications, and whether susceptible individuals can be identified in childhood, is unknown. The third major objective of these studies of secondary features is to determine the incidence of basilar invagination and develop a monitoring and management plan for this neurological feature. Next, the prevalence, severity, age of onset and genotypic/phenotypic correlation of hearing loss among children with types II and IV OI remains poorly understood; therefore, the study of audiological features is our fourth major objective. The final major objective in this study is the continued study of the genetic and molecular biology aspect of OI. Patients will have skin biopsies for collagen studies at the biochemical and molecular level. Parents will have blood drawn for determination of mosaic status for the mutation that causes their child s OI. These studies will provide further information on genotype/phenotype correlation and other variables in OI genetics. As appropriate, bone chips from emergency or elective surgical procedures on the participants will be used to study osteoblast function in OI.
- Conditions
- Osteogenesis Imperfecta
- Keywords
- Natural History, Brittle Bone, Connective Tissue, Osteogenesis Imperfecta
- Medical subject headings
- Osteogenesis Imperfecta
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Children with OI | Children with OI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ambulation, Basilar Invagination, Secondary Effects of OI
For the younger children, we evaluated bone density, physical function, dental manifestations, and the cardiovascular, pulmonary, and audiologic systems. Visits for children under 5 will be every 4 months. These assessments will continue when the participants turn 5, with the addition of the neurological system. All children ages 5-18 years will be evaluated at the Clinical Center every 6 months. Ages 19- will be seen on an annual basis
Measured: age-based
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study start29 Jan 1997
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Osteogenesis ImperfectaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Joshua J Zimmerberg, M.D., Principal investigator, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001594
- Sponsor's protocol ID
- 970064
- Other IDs
- 97-CH-0064
- Status last verified
- 6 Jul 2026
- First submitted
- 3 Nov 1999
- Last updated
- 28 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Due to the data in this natural history study being open and utilized in comparison with another currently open, longitudinal, natural history study, we would wait for that open study to meet its primary and secondary endpoints prior to making the plan to make IPD available.
Publications
Marini JC. Osteogenesis imperfecta: comprehensive management. Adv Pediatr. 1988;35:391-426. No abstract available.
PubMed 3055864Marini JC, Bordenick S, Heavner G, Rose S, Hintz R, Rosenfeld R, Chrousos GP. The growth hormone and somatomedin axis in short children with osteogenesis imperfecta. J Clin Endocrinol Metab. 1993 Jan;76(1):251-6. doi: 10.1210/jcem.76.1.8421094.
PubMed 8421094Charnas LR, Marini JC. Communicating hydrocephalus, basilar invagination, and other neurologic features in osteogenesis imperfecta. Neurology. 1993 Dec;43(12):2603-8. doi: 10.1212/wnl.43.12.2603.
PubMed 8255464
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation and Intervention for Ambulation, Growth, and Basilar Invagination in Osteogenesis Imperfecta
- ClinicalTrials.gov ID
- NCT00001594
- Acronym / sponsor ID
- 970064
- Conditions
- Osteogenesis Imperfecta
- Keywords
- Natural History, Brittle Bone, Connective Tissue, Osteogenesis Imperfecta
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 88 participants (actual)
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Study start
- 29 Jan 1997 (actual)
- First posted
- 4 Nov 1999 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
We propose a longitudinal study of the natural history of types III and IV osteogenesis imperfecta for children age birth to 25 years. A consistent objective throughout this study is to obtain a comprehensive assessment of the natural history and progression of the multiple secondary features of osteogenesis imperfecta. In addition to radiographic, bone density, physical rehabilitation and dental manifestations, we will assess the cardiovascular, pulmonary, neurological, and audiology systems.
The major objectives of this protocol focus on rehabilitation and physical therapy studies, pulmonary and cardiovascular function, neurological features, audiological studies and genetic and molecular biology aspects of OI. A major objective in this study is to expand the intensive rehabilitation and physical therapy studies of children with types III and IV OI. This objective continues the work that has been done in the Rehabilitation Department of the Clinical Center for the past 20 years on these patients. However, the focus of this objective is changing to include studies of scoliosis and its effect on function, studies of chest proportions and rib deformities, and studies of nonkinetic variables related to motor performance, such as temperament, competence, coping, and resilience in children with OI. The second major objective is the longitudinal study of pulmonary function in children with types III and IV OI. It is well known that cardiopulmonary complications are a major cause of disability and death in adults with OI; the developmental patterns of these complications, and whether susceptible individuals can be identified in childhood, is unknown. The third major objective of these studies of secondary features is to determine the incidence of basilar invagination and develop a monitoring and management plan for this neurological feature. Next, the prevalence, severity, age of onset and genotypic/phenotypic correlation of hearing loss among children with types II and IV OI remains poorly understood; therefore, the study of audiological features is our fourth major objective. The final major objective in this study is the continued study of the genetic and molecular biology aspect of OI. Patients will have skin biopsies for collagen studies at the biochemical and molecular level. Parents will have blood drawn for determination of mosaic status for the mutation that causes their child s OI. These studies will provide further information on genotype/phenotype correlation and other variables in OI genetics. As appropriate, bone chips from emergency or elective surgical procedures on the participants will be used to study osteoblast function in OI.
Detailed description
We propose a longitudinal study of the natural history of types III and IV osteogenesis imperfecta for children age birth to 30 years. A consistent objective throughout this study is to obtain a comprehensive assessment of the natural history and progression of the multiple secondary features of osteogenesis imperfecta. In addition to radiographic, bone density, physical rehabilitation and dental manifestations, we will assess the cardiovascular, pulmonary, neurological, and audiology systems.
The major objectives of this protocol focus on rehabilitation and physical therapy studies, pulmonary and cardiovascular function, neurological features, audiological studies and genetic and molecular biology aspects of OI. A major objective in this study is to expand the intensive rehabilitation and physical therapy studies of children with types III and IV OI. This objective continues the work that has been done in the Rehabilitation Department of the Clinical Center for the past 20 years on these patients. However, the focus of this objective is changing to include studies of scoliosis and its effect on function, studies of chest proportions and rib deformities, and studies of nonkinetic variables related to motor performance, such as temperament, competence, coping, and resilience in children with OI. The second major objective is the longitudinal study of pulmonary function in children with types III and IV OI. It is well known that cardiopulmonary complications are a major cause of disability and death in adults with OI; the developmental patterns of these complications, and whether susceptible individuals can be identified in childhood, is unknown. The third major objective of these studies of secondary features is to determine the incidence of basilar invagination and develop a monitoring and management plan for this neurological feature. Next, the prevalence, severity, age of onset and genotypic/phenotypic correlation of hearing loss among children with types II and IV OI remains poorly understood; therefore, the study of audiological features is our fourth major objective. The final major objective in this study is the continued study of the genetic and molecular biology aspect of OI. Patients will have skin biopsies for collagen studies at the biochemical and molecular level. Parents will have blood drawn for determination of mosaic status for the mutation that causes their child s OI. These studies will provide further information on genotype/phenotype correlation and other variables in OI genetics. As appropriate, bone chips from emergency or elective surgical procedures on the participants will be used to study osteoblast function in OI.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Children with OI | – | –Children with OI |
Who may qualify
- Ages
- Up to 10 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Children will be recruited from the United States. This recruitment will be accomplished by our contacts with the Osteogenesis Imperfecta Foundation, parent-to-parent communication, and outside referrals from other health care providers
Key inclusion criteria (5 listed)
- Children will be recruited from the United States. This recruitment will be accomplished by our contacts with the Osteogenesis Imperfecta Foundation, parent-to-parent communication, and outside referrals from other health care providers.
- There are no exclusionary criteria related to race or gender for this protocol.
- Children enrolled in this study will be limited to those with Sillence Types III and IV OI, as determined by clinical and genetic criteria.
- Patients age birth to 10 years at enrollment will be considered for this protocol.
- Children who have not had skin biopsy done for collagen analysis at another facility are preferred for participation in this study. However, previous skin biopsy at another facility will not preclude participation in this protocol.
Key exclusion criteria (6 listed)
- Children who can be expected to attain at least some degree of ambulatory skill or have high potential for achieving independent locomotion with assistive technology.
- Children who are clinically too severe to benefit from this program are defined by the following criteria:
- The ratio of head circumference age (the age for which the child's head or body size falls at the 50th percentile) to body length age (the age for which the child's length falls at the 50th percentile) is 7:1 or greater;
- Children who are 24 months of age, and who are unable to sit unsupported for 60 seconds and are unable to demonstrate the ability to prop themselves on upper extremities in the prone position;
- Children who have other significant medical problems, especially severe cardiopulmonary problems, which have an impact on their physical development.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Ambulation, Basilar Invagination, Secondary Effects of OI
Time frame: age-based
For the younger children, we evaluated bone density, physical function, dental manifestations, and the cardiovascular, pulmonary, and audiologic systems. Visits for children under 5 will be every 4 months. These assessments will continue when the participants turn 5, with the addition of the neurological system. All children ages 5-18 years will be evaluated at the Clinical Center every 6 months. Ages 19- will be seen on an annual basis
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2026.
- Background: PubMed 3055864Marini JC. Osteogenesis imperfecta: comprehensive management. Adv Pediatr. 1988;35:391-426. No abstract available.
- Background: PubMed 8421094Marini JC, Bordenick S, Heavner G, Rose S, Hintz R, Rosenfeld R, Chrousos GP. The growth hormone and somatomedin axis in short children with osteogenesis imperfecta. J Clin Endocrinol Metab. 1993 Jan;76(1):251-6. doi: 10.1210/jcem.76.1.8421094.
- Background: PubMed 8255464Charnas LR, Marini JC. Communicating hydrocephalus, basilar invagination, and other neurologic features in osteogenesis imperfecta. Neurology. 1993 Dec;43(12):2603-8. doi: 10.1212/wnl.43.12.2603.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. Due to the data in this natural history study being open and utilized in comparison with another currently open, longitudinal, natural history study, we would wait for that open study to meet its primary and secondary endpoints prior to making the plan to make IPD available.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joshua J Zimmerberg, M.D. principal investigator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Osteogenesis Imperfecta, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ambulation, Basilar Invagination, Secondary Effects of OI (time frame: age-based). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001594, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2026.