Developmental Bone DiseaseNCT00001754
Study of Skeletal Disorders and Short Stature
An observational study of Developmental Bone Disease and Dwarfism, run by National Human Genome Research Institute (NHGRI) at 1 site in United States.
Trial summary
This study will determine the genes responsible for skeletal dysplasias (disorders of the skeleton) and short stature and define the range and type of medical problems they cause over time. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Developmental Bone Disease, Dwarfism, Skeletal Dysplasias
- How many people
- 600 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 1998to May 2001
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Patients with known or suspected skeletal dysplasias or short stature and their family members of any age will be recruited worldwide from diverse medical communities including genetics, orthopedics, ophthalmology, and pediatrics.
DISEASE CATEGORY I:
Individuals and family members with a suspected or an established diagnosis of any FGFR3 disorder, type II collagen disorder, Schmid metaphyseal dysplasia, pyknodysostosis, proximal symphalangism, or brachydactyly type C.
DISEASE CATEGORY II:
Individuals and family members with a suspected or an established diagnosis of a skeletal dysplasia in which the disease gene is not yet known, including: Ellis van Crevald, brachydactyly types B and E, and cartilage-hair hypoplasia.
DISEASE CATEGORY III:
Individuals and family members who have previously uncharacterized systemic manifestations suggestive of a skeletal dysplasias, with clinical findings of: disproportionate or proportionate short stature; and/or cleft palate; and/or detached retina; and/or history of loose joints or frequent joint dislocation; and/or history of, or family history of, premature arthritis.
Short Stature Category I: Individuals with generalized short stature and their family members. This includes adults with abnormal stature as statistically defined from standardized growth charts.
Must be able to give informed consent, older children (greater than or equal to 7 years old) who do not give assent, or persons who are wards of the state will be excluded from the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Human Genome Research Institute (NHGRI)
Bethesda, Maryland, 20892
About this study
Official title: Clinical and Molecular Manifestations of Human Skeletal Dysplasias and Short Stature
This study will determine the genes responsible for skeletal dysplasias (disorders of the skeleton) and short stature and define the range and type of medical problems they cause over time. It will investigate whether specific gene changes cause specific medical problems in these disorders and identify the signs and symptoms upon which their diagnoses must be based.
Individuals with short stature or with a skeletal dysplasia known or suspected to be caused by a gene mutation (change) may be eligible for this study. Family members may also participate. Skeletal dysplasias under study include: achondroplasia, hypochondroplasia, achondrogenesis type II, hypochondrogenesis, Kniest dysplasia, spondyloepiphyseal dysplasias, Stickler syndrome; Shmid and Jansen metaphyseal dysplasias; pyknodysotosis, proximal symphalangism, brachydactyly types B C and E, Ellis van Creveld and related disorders, metatrophic chondrodysplasias, cartilage-hair hypoplasia and disorders with a skeletal abnormality that have not yet been defined but might be the result of a genetic defect.
Read more
Patients will talk with two genetics specialists who will explain the study and its possible implications for the patient and family and answer questions. The patient's medical records will be reviewed, a personal and family history will be taken, and a physical examination will be done. Various other procedures that may be done include drawing up to 6 tablespoons of blood, some of which will be used for DNA (genetic) studies, X-rays, echocardiography (ultrasound of the heart), magnetic resonance imaging (MRI), eye examination, hearing test, sleep study, sperm analysis and skin biopsy (surgical removal of a small piece of skin done under local anesthetic). There may be additional evaluations by specialists in rheumatology, rehabilitation medicine and orthopedics. When the tests and examinations are completed (after 2 to 3 days), a doctor will discuss the results with the patient. Patients whose DNA studies show that a gene change is responsible for their disorder will meet with a genetics nurse or counselor to review the results, express their feelings and ask any questions they may have. Patients may be asked to return to NIH every 6 months to 2 years for continued follow-up. Medical management will be provided primarily by the patient's own physician.
Participating family members will be interviewed by telephone about their personal and family health history and will have a blood sample drawn for DNA testing. If a gene change is found that is responsible for the bone disorder or growth problem in the family, arrangements will be made for the family member to discuss the implications of the findings with a genetics specialist.
Read the detailed description
We will investigate the clinical manifestations and molecular genetic defects of human skeletal dysplasias and generalized short stature. Families with skeletal dysplasias or short stature of known or suspected genetic basis will be enrolled. Affected individuals or individuals suspected of having a skeletal dysplasia will undergo periodic clinical assessment and genetic analyses for the purpose of: 1) definition and characterization of phenotype, 2) determination of the natural history of the disorder, and 3) genotype/phenotype correlation. Genetic linkage studies may be performed for disorders in which the genetic bases is not yet known.
- Conditions
- Developmental Bone Disease, Dwarfism, Skeletal Dysplasias
- Keywords
- Dwarfism, Gene Mapping, Linkage, Mutation Analysis, Skeletal Biology, Brachydactyly Types C & E, Cartilage-Hair Hypoplasia, Ellis Van Crevald, FgFR-3, Proximal Symphalangism, Pyknodysotosis, Schmid Metaphyseal, Short Stature, Skeletal Dysplasia, Type II Collagen Disorder
- Medical subject headings
- Bone Diseases, Developmental, Dwarfism, Cartilage-hair hypoplasia, Cushing's symphalangism, Mucopolysaccharidosis IV
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2002 (estimated)
- Study startJun 1998
- Study completionMay 2001
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 Developmental Bone DiseaseStudies 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
- Enrolment
- 600 participants
Sponsor and investigators
- Lead sponsor
- National Human Genome Research Institute (NHGRI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001754
- Sponsor's protocol ID
- 980119
- Other IDs
- 98-HG-0119
- Status last verified
- Jun 2000
- First submitted
- 3 Nov 1999
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Bellus GA, Hefferon TW, Ortiz de Luna RI, Hecht JT, Horton WA, Machado M, Kaitila I, McIntosh I, Francomano CA. Achondroplasia is defined by recurrent G380R mutations of FGFR3. Am J Hum Genet. 1995 Feb;56(2):368-73.
PubMed 7847369Bellus GA, McIntosh I, Smith EA, Aylsworth AS, Kaitila I, Horton WA, Greenhaw GA, Hecht JT, Francomano CA. A recurrent mutation in the tyrosine kinase domain of fibroblast growth factor receptor 3 causes hypochondroplasia. Nat Genet. 1995 Jul;10(3):357-9. doi: 10.1038/ng0795-357.
PubMed 7670477Bogaert R, Tiller GE, Weis MA, Gruber HE, Rimoin DL, Cohn DH, Eyre DR. An amino acid substitution (Gly853-->Glu) in the collagen alpha 1(II) chain produces hypochondrogenesis. J Biol Chem. 1992 Nov 5;267(31):22522-6.
PubMed 1429602
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical and Molecular Manifestations of Human Skeletal Dysplasias and Short Stature
- ClinicalTrials.gov ID
- NCT00001754
- Acronym / sponsor ID
- 980119
- Conditions
- Developmental Bone Disease, Dwarfism, Skeletal Dysplasias
- Keywords
- Dwarfism, Gene Mapping, Linkage, Mutation Analysis, Skeletal Biology, Brachydactyly Types C & E, Cartilage-Hair Hypoplasia, Ellis Van Crevald
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 600 participants
- Lead sponsor
- National Human Genome Research Institute (NHGRI)US National Institutes of Health
- Study start
- Jun 1998
- Study completion
- May 2001
- First posted
- 10 Dec 2002 (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.
This study will determine the genes responsible for skeletal dysplasias (disorders of the skeleton) and short stature and define the range and type of medical problems they cause over time. It will investigate whether specific gene changes cause specific medical problems in these disorders and identify the signs and symptoms upon which their diagnoses must be based.
Individuals with short stature or with a skeletal dysplasia known or suspected to be caused by a gene mutation (change) may be eligible for this study. Family members may also participate. Skeletal dysplasias under study include: achondroplasia, hypochondroplasia, achondrogenesis type II, hypochondrogenesis, Kniest dysplasia, spondyloepiphyseal dysplasias, Stickler syndrome; Shmid and Jansen metaphyseal dysplasias; pyknodysotosis, proximal symphalangism, brachydactyly types B C and E, Ellis van Creveld and related disorders, metatrophic chondrodysplasias, cartilage-hair hypoplasia and disorders with a skeletal abnormality that have not yet been defined but might be the result of a genetic defect.
Patients will talk with two genetics specialists who will explain the study and its possible implications for the patient and family and answer questions. The patient's medical records will be reviewed, a personal and family history will be taken, and a physical examination will be done. Various other procedures that may be done include drawing up to 6 tablespoons of blood, some of which will be used for DNA (genetic) studies, X-rays, echocardiography (ultrasound of the heart), magnetic resonance imaging (MRI), eye examination, hearing test, sleep study, sperm analysis and skin biopsy (surgical removal of a small piece of skin done under local anesthetic). There may be additional evaluations by specialists in rheumatology, rehabilitation medicine and orthopedics. When the tests and examinations are completed (after 2 to 3 days), a doctor will discuss the results with the patient. Patients whose DNA studies show that a gene change is responsible for their disorder will meet with a genetics nurse or counselor to review the results, express their feelings and ask any questions they may have. Patients may be asked to return to NIH every 6 months to 2 years for continued follow-up. Medical management will be provided primarily by the patient's own physician.
Participating family members will be interviewed by telephone about their personal and family health history and will have a blood sample drawn for DNA testing. If a gene change is found that is responsible for the bone disorder or growth problem in the family, arrangements will be made for the family member to discuss the implications of the findings with a genetics specialist.
Detailed description
We will investigate the clinical manifestations and molecular genetic defects of human skeletal dysplasias and generalized short stature. Families with skeletal dysplasias or short stature of known or suspected genetic basis will be enrolled. Affected individuals or individuals suspected of having a skeletal dysplasia will undergo periodic clinical assessment and genetic analyses for the purpose of: 1) definition and characterization of phenotype, 2) determination of the natural history of the disorder, and 3) genotype/phenotype correlation. Genetic linkage studies may be performed for disorders in which the genetic bases is not yet known.
Study design
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
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
Not reported in the source record.
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 4 Mar 2008.
- Background: PubMed 7847369Bellus GA, Hefferon TW, Ortiz de Luna RI, Hecht JT, Horton WA, Machado M, Kaitila I, McIntosh I, Francomano CA. Achondroplasia is defined by recurrent G380R mutations of FGFR3. Am J Hum Genet. 1995 Feb;56(2):368-73.
- Background: PubMed 7670477Bellus GA, McIntosh I, Smith EA, Aylsworth AS, Kaitila I, Horton WA, Greenhaw GA, Hecht JT, Francomano CA. A recurrent mutation in the tyrosine kinase domain of fibroblast growth factor receptor 3 causes hypochondroplasia. Nat Genet. 1995 Jul;10(3):357-9. doi: 10.1038/ng0795-357.
- Background: PubMed 1429602Bogaert R, Tiller GE, Weis MA, Gruber HE, Rimoin DL, Cohn DH, Eyre DR. An amino acid substitution (Gly853-->Glu) in the collagen alpha 1(II) chain produces hypochondrogenesis. J Biol Chem. 1992 Nov 5;267(31):22522-6.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Developmental Bone Disease and Dwarfism, run by National Human Genome Research Institute (NHGRI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. 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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001754, 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 4 Mar 2008.