Skeletal DysplasiaNCT02762318
Identification and Characterization of Bone-related Genetic Variants in Families
An observational study of Skeletal Dysplasia, run by Weill Medical College of Cornell University at 1 site in Qatar.
Trial summary
Identify novel genetic variants causing skeletal dysplasia in Qatari populations and to additionally develop an understanding of how those variants influence skeletal biology at a molecular and cellular level. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Skeletal Dysplasia
- What is being tested?
- Samples With DNA
- How many people
- 5 participants
- Where
- 1 siteQatar
- Study dates
- Dec 2015to Jul 2020
- 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
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: All our subjects will be recruited from the pool of patients seen by the Pediatric Orthopedic Consultants at the Bone and Joint Institute. Subjects will be coming to the clinic for their standard care. They will be identified during that visit as candidates for the study.
Who may be able to join
- All included individuals must provide informed consent
- Patients identified to have a skeletal dysplasia
- All ethnic backgrounds are acceptable
- Disease must be genetic with no evident environmental cause.
- Evidence of Mendelian Transmission determined by fulfilling one of the following criteria:
- Multiple affected family members (at least first-degree relative with disease)
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- History of consanguinity
- Severe disease in newborn in the absence of family history
- Syndromic disease in single individuals
- Congenital abnormality affecting major organ system(s)
- Mendelianized extremes of common disease (e.g. bilateral developmental dysplasia of the hip)
- All ages will be included
- Rare diseases or rare forms of known diseases
- Unaffected family members or relatives of the individual with the primary syndrome
Who cannot join
- Individuals who do not consent will not be included
- Individuals for which a molecular diagnosis has already been established by alternative method (e.g. karyotype or known gene mutation)
- Diseases for which an environmental factor is most likely the cause (e.g. Traumatic bone injury or Rickets)
- Diseases of which late age of onset rule out Mendelian transmission
- Common Diseases for which late age of onset rule out Mendelian transmission (e.g.Osteoporosis)
Trial locations and contacts
1 site in 1 country.
About this study
Identify novel genetic variants causing skeletal dysplasia in Qatari populations and to additionally develop an understanding of how those variants influence skeletal biology at a molecular and cellular level.
Read the detailed description
To identify novel genetic variants causing skeletal dysplasia in Qatari populations and to additionally develop an understanding of how those variants influence skeletal biology at a molecular and cellular level.
Achieving this goal will be split into two aims:
- Aim 1: Perform a clinical characterization of a study group of patients with various forms of skeletal dysplasia seen in pediatric orthopedics clinic at Hamad Medical center, HMC. This will be followed by whole exome or genome sequencing and analysis to search for novel pathogenic variants responsible for the clinical presentation of these patients
- Aim 2: The genes and variants identified in Aim 1 will be characterized to determine their effects on osteoblast and chondrocyte differentiation and function.
All the subjects will be recruited from the pool of patients seen by the Pediatric Orthopedic Consultants at the Bone and Joint Institute. Subjects will be coming to the clinic for their standard care. They will be identified during that visit as candidates for the study. They will then be told about the study by their physicians. If a patient is interested in participation, the physician will introduce the CRC to him/her who will proceed with the consent process.
Consenting and the study procedures might be performed during that same visit if time allows, or in a new scheduled visit arranged at that time.
This research will also involve a pedigree creation. Secondary subjects (family members or relatives) will be told about the study by the research subject. The secondary subject will be able to read a copy of the consent form, think of his participation, and if interested they will be told to contact the Investigators. A suitable time will then be arranged, by an appropriate member of the research team, for the secondary subject to visit the clinic in order to proceed with the consent process and the study procedures.
- Conditions
- Skeletal Dysplasia
- Being tested
- Samples With DNA
- Medical subject headings
- Mucopolysaccharidosis IV
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Samples With DNAOther
After consenting, all subjects have to undergo the following procedures:
Up to 25 ml of blood will be withdrawn. If for any reason, the blood sample cannot be obtained, a swab will be applied to the inside of the cheek to obtain saliva.
A questionnaire will be used to collect information about individual A routine physical exam will be performed. The subject's medical record will be reviewed To well document some of the specific phenotypes and conditions, physicians might take photographs of the affected body area.
For secondary subjects (relatives or family members), normal examination and routine lab tests/ imagining will be done if needed as per the related standard care.
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical assessement of a study group of patients with various forms of skeletal dysplasia, followed by identification of novel pathogenic variants using whole exome/genome sequencing.
Patients will be selected for the study and will undergo:
Phenotyping by a combination of clinical history taking and examination, determination of bone mass, laboratory studies, Full exome sequencing Lastly, the variants present in each exome will be determined, and these variants will be classified according to their likelihood of being pathogenic.
Measured: 2-3 years
Secondary outcomes (1)
Biochemical and cellular characterization of the putative causative genes.
Chondrocytes or osteoblasts will be used to measure the following:
Putative gene expression in the skeletal system, How they influence osteoblast and chondrocyte differentiation how they alter the activity of the key molecular pathways governing the activity of osteoblasts and chondrocytes,
Measured: 1-2 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2016 (estimated)
- Study startDec 2015
- Primary completionJul 2020
- Study completionJul 2020
Why it stopped: Lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Skeletal DysplasiaStudies of the same condition, open and under way.
- More trials run by Weill Medical College of Cornell UniversityThe sponsor's other registered studies.
- 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
- Family based
- Time perspective
- Prospective
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Collaborators
- Hamad Medical Corporation
- Responsible party
- Sponsor
- Investigators
- Ronald Crystal, MD, Principal investigator, Weill Medical College of Cornell University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02762318
- Sponsor's protocol ID
- 14-00098
- Status last verified
- Apr 2023
- First submitted
- 16 Dec 2015
- Last updated
- 19 Apr 2023
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: To facilitate future genetic diagnostics related to skeletal dysplasias, the variants identified and their classifications will be shared in Gulf-based health forums and the international online databases of clinically significant genetic variation in humans (ie Clinvar, dbSNP). The data gathered regarding the spectrum of disorders identified will be similarly disseminated. HMC-affiliated investigators will use the data generated for poster and oral presentations at international meetings. Similarly, the genetic data will be likewise shared at the relevant local and international meetings. Most importantly, we are committed to publishing the results in a timely fashion in the biomedical literature, aiming for publications in high quality, high impact, peer reviewed journals. All original data and reagents generated will be made available to other investigators according to the conventions of biomedical science.
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identification and Characterization of Bone-related Genetic Variants in Families
- ClinicalTrials.gov ID
- NCT02762318
- Acronym / sponsor ID
- 14-00098
- Conditions
- Skeletal Dysplasia
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Lack of funding
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Weill Medical College of Cornell UniversityUniversity, hospital or other
- Collaborators
- Hamad Medical Corporation
- Study start
- Dec 2015
- Primary completion
- Jul 2020 (actual)
- Study completion
- Jul 2020 (actual)
- First posted
- 4 May 2016 (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.
Identify novel genetic variants causing skeletal dysplasia in Qatari populations and to additionally develop an understanding of how those variants influence skeletal biology at a molecular and cellular level.
Detailed description
To identify novel genetic variants causing skeletal dysplasia in Qatari populations and to additionally develop an understanding of how those variants influence skeletal biology at a molecular and cellular level.
Achieving this goal will be split into two aims:
- Aim 1: Perform a clinical characterization of a study group of patients with various forms of skeletal dysplasia seen in pediatric orthopedics clinic at Hamad Medical center, HMC. This will be followed by whole exome or genome sequencing and analysis to search for novel pathogenic variants responsible for the clinical presentation of these patients
- Aim 2: The genes and variants identified in Aim 1 will be characterized to determine their effects on osteoblast and chondrocyte differentiation and function.
All the subjects will be recruited from the pool of patients seen by the Pediatric Orthopedic Consultants at the Bone and Joint Institute. Subjects will be coming to the clinic for their standard care. They will be identified during that visit as candidates for the study. They will then be told about the study by their physicians. If a patient is interested in participation, the physician will introduce the CRC to him/her who will proceed with the consent process.
Consenting and the study procedures might be performed during that same visit if time allows, or in a new scheduled visit arranged at that time.
This research will also involve a pedigree creation. Secondary subjects (family members or relatives) will be told about the study by the research subject. The secondary subject will be able to read a copy of the consent form, think of his participation, and if interested they will be told to contact the Investigators. A suitable time will then be arranged, by an appropriate member of the research team, for the secondary subject to visit the clinic in order to proceed with the consent process and the study procedures.
Study design
- Observational model
- Family based
- Time perspective
- Prospective
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- All our subjects will be recruited from the pool of patients seen by the Pediatric Orthopedic Consultants at the Bone and Joint Institute. Subjects will be coming to the clinic for their standard care. They will be identified during that visit as candidates for the study.
Key inclusion criteria (14 listed)
- All included individuals must provide informed consent
- Patients identified to have a skeletal dysplasia
- All ethnic backgrounds are acceptable
- Disease must be genetic with no evident environmental cause.
- Evidence of Mendelian Transmission determined by fulfilling one of the following criteria:
Key exclusion criteria (5 listed)
- Individuals who do not consent will not be included
- Individuals for which a molecular diagnosis has already been established by alternative method (e.g. karyotype or known gene mutation)
- Diseases for which an environmental factor is most likely the cause (e.g. Traumatic bone injury or Rickets)
- Diseases of which late age of onset rule out Mendelian transmission
- Common Diseases for which late age of onset rule out Mendelian transmission (e.g.Osteoporosis)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Samples With DNAAfter consenting, all subjects have to undergo the following procedures: Up to 25 ml of blood will be withdrawn. If for any reason, the blood sample cannot be obtained, a swab will be applied to the inside of the cheek to obtain saliva. A questionnaire will be used to collect information about individual A routine physical exam will be performed. The subject's medical record will be reviewed To well document some of the specific phenotypes and conditions, physicians might take photographs of the affected body area. For secondary subjects (relatives or family members), normal examination and routine lab tests/ imagining will be done if needed as per the related standard care. | Other | – |
Primary outcome
Clinical assessement of a study group of patients with various forms of skeletal dysplasia, followed by identification of novel pathogenic variants using whole exome/genome sequencing.
Time frame: 2-3 years
Patients will be selected for the study and will undergo: Phenotyping by a combination of clinical history taking and examination, determination of bone mass, laboratory studies, Full exome sequencing Lastly, the variants present in each exome will be determined, and these variants will be classified according to their likelihood of being pathogenic.
1 secondary outcome
Biochemical and cellular characterization of the putative causative genes.
Time frame: 1-2 year
Results and safety
The study was stopped early (reason given: Lack of funding). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2023.
- Individual participant dataSharing planned: Yes. To facilitate future genetic diagnostics related to skeletal dysplasias, the variants identified and their classifications will be shared in Gulf-based health forums and the international online databases of clinically significant genetic variation in humans (ie Clinvar, dbSNP). The data gathered regarding the spectrum of disorders identified will be similarly disseminated. HMC-affiliated investigators will use the data generated for poster and oral presentations at international meetings. Similarly, the genetic data will be likewise shared at the relevant local and international meetings. Most importantly, we are committed to publishing the results in a timely fashion in the biomedical literature, aiming for publications in high quality, high impact, peer reviewed journals. All original data and reagents generated will be made available to other investigators according to the conventions of biomedical science.
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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.
Ronald Crystal, MD principal investigator
Weill Medical College of Cornell University
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 Skeletal Dysplasia, run by Weill Medical College of Cornell University at 1 site in Qatar.
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 14 inclusion and 5 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: stopped early, as of the sponsor's last update on 19 Apr 2023. 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 Qatar. 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 was stopped early (reason given: Lack of funding). Results are not available in the source record.
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?
Clinical assessement of a study group of patients with various forms of skeletal dysplasia, followed by identification of novel pathogenic variants using whole exome/genome sequencing. (time frame: 2-3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Apr 2023.