Ehlers-Danlos SyndromeNCT00270686
Studies of Heritable Disorders of Connective Tissue
An observational study of Ehlers-Danlos Syndrome and Stickler Syndrome, run by National Institute on Aging (NIA) at 1 site in United States.
Trial summary
Background: Heritable disorders of connective tissue are genetic conditions that can affect the skin and other parts of the body. They are related to mutations in genes that are responsible for building tissues. The symptoms differ among disorders. Read more about this study
- Who is it for?
- Ages 2 years and olderHealthy volunteers can take part
- Conditions the study is for
- Ehlers-Danlos Syndrome, Stickler Syndrome, Marfan Syndrome
- How many people
- 929 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Jan 2003to 2 Jan 2015
- 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 2 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Individuals and their family members will be offered enrollment if they have an established or suspected diagnosis of Marfan, Stickler, or Ehlers-Danlos syndrome, or Overlap connective tissue disorder.
- Determination of eligibility will be made by review of prior records.
- In some cases, a screening evaluation to establish the diagnosis may be performed subjects may be excluded from further participation if the diagnosis is ruled out. Cytogenetic analysis may be necessary to rule out a chromosomal abnormality that has overlapping features with HDCT.
- Clinical inclusion criteria require: personal or family history of one or more of the following features in a pattern suggestive of a heritable connective tissue disorder: Marfanoid body habitus, aortic dilatation and/or dissection, ectopia lentis, detached retina, vitreous degeneration and/or early onset high myopia, posterior cleft palate, joint laxity and/or dislocation, premature osteoarthritis, skin fragility, striae, easy bruising and/or hyperextensibile skin, pectus excavatum or carinatum, scoliosis, spondylolisthesis and/or dural ectasia, Chiari I Malformation, high frequency sensorineural hearing loss, fibromuscular dysplasia of arteries, aneurysms.
Who cannot join
- The only exclusion criterion is inability to provide informed consent, or the absence of a guardian who is authorized to provide informed consent in the case of minor subjects.
- There will be no exclusion based upon age, gender, ethnicity, socioeconomic status, or any other factor except ability to provide informed consent.
- Pregnant and nursing women may be limited in their participation in some aspects of the study (e.g. ionizing radiation exposure or MRI) during the time that they are pregnant or nursing.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Aging, Clinical Research Unit
Baltimore, Maryland, 21224
About this study
Official title: Clinical and Molecular Manifestations of Heritable Disorders of Connective Tissue
Background:
- Heritable disorders of connective tissue are genetic conditions that can affect the skin and other parts of the body. They are related to mutations in genes that are responsible for building tissues. The symptoms differ among disorders. Researchers want to study which genes may be responsible for different disorders. They will be performing a long-term (up to 10 years) study and a study that requires a single visit. These studies will look at how these disorders affect the body and what genes may cause these conditions.
Read more
Objectives:
- To perform one-time and long-term studies of people who have heritable disorders of connective tissue.
Eligibility:
- Individuals at least 2 years of age who have or may have a heritable disorder of connective tissue.
Design:
- Participants will be screened with a physical exam, medical history, and blood samples.
- Participants will be on one of two parts of this study. The longitudinal arm will require long-term study over about 10 years. The mutational analysis arm will involve a single visit.
- Longitudinal arm participants must be at least 12 years of age. They will have study visits at regular intervals for up to 10 years. The tests given at these visits may include all or some of the following:
- Blood, saliva, urine, and skin samples
- Heart and lung function tests
- Magnetic resonance imaging scans of the neck, chest, spine, and abdomen
- Other imaging studies such as x-rays, bone density scans, and ultrasounds
- Questionnaires about sleep, pain, and quality of life
- Photographs of affected areas.
- Mutational analysis arm participants will have a single study visit. They will provide blood and saliva samples. They will provide tissue from a skin biopsy. They will also let the researchers take photos of any affected body parts. They will complete questionnaires about sleep, pain, and quality of life.
Read the detailed description
Heritable disorders of connective tissue are a heterogenous group of genetic conditions caused by defects of extracellular matrix elements such as collagen, elastin, mucopolysaccharides or related biomolecules. The genetic cause of many connective tissue disorders has been elucidated, while others are yet to be discovered or further defined. While clinical diagnostic criteria have been established for several of the connective tissue syndromes, many share features that overlap the known descriptions of other connective tissue disorders. Therefore, further characterization and phenotype/genotype correlation is needed to adequately diagnose and find treatments for these yet-to-be genotyped disorders.
An aim of this work is the examination of the cardiovascular, musculoskeletal and neurological complications of heritable connective tissue disorders (HDCT) and the natural history of these complications. Through mutational analysis for genes known to cause the HDCT, as well as identification of new genes, we will assess the relationship between specific mutations and their associated disease phenotypes. Through the analysis of tissue specimens obtained from patients with HDCT, we will identify the biochemical pathways that lead to connective tissue fragility. We will continue to assess the severity, prevalence, and pattern of pain and related psychological and quality of life dimensions in HDCT.
The resulting understanding of genotype/phenotype correlations and biochemical pathways will enhance our understanding of connective tissue biology. This knowledge has the potential to lead to new treatments for not only patients with HDCT, but also for pathological conditions associated with the weakness of connective tissues in aging.
- Conditions
- Ehlers-Danlos Syndrome, Stickler Syndrome, Marfan Syndrome
- Keywords
- Ehlers-Danlos Syndrome, Stickler Syndrome, Marfan Syndrome, Genetics, Aneurysm
- Medical subject headings
- Ehlers-Danlos Syndrome, Stickler syndrome, type 1, Marfan Syndrome, Aneurysm
What is being measured
The primary outcome is the main question the study is designed to answer.
Description of natural history of Hereditary Disorders of Connective Tissue (HDCT)
Measured: Ongoing
Genetic analysis to identify novel genes that cause HDCT
Measured: Ongoing
Biochemical analysis of biospecimens to identify correlations with disease activity and progress
Measured: Ongoing
Identification of disease treatment targets
Measured: Ongoing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2005 (estimated)
- Study start21 Jan 2003
- Study completion2 Jan 2015
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 Ehlers-Danlos SyndromeStudies 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
- Time perspective
- Prospective
- Enrolment
- 929 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute on Aging (NIA)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Nazli B McDonnell, M.D., Principal investigator, National Institute on Aging (NIA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00270686
- Sponsor's protocol ID
- 999903330
- Other IDs
- 03-AG-N330
- Status last verified
- 2 Jan 2015
- First submitted
- 27 Dec 2005
- Last updated
- 5 Apr 2018
- Results posted
- No
Publications
Ainsworth SR, Aulicino PL. A survey of patients with Ehlers-Danlos syndrome. Clin Orthop Relat Res. 1993 Jan;(286):250-6.
PubMed 8425354Beighton P, de Paepe A, Danks D, Finidori G, Gedde-Dahl T, Goodman R, Hall JG, Hollister DW, Horton W, McKusick VA, et al. International Nosology of Heritable Disorders of Connective Tissue, Berlin, 1986. Am J Med Genet. 1988 Mar;29(3):581-94. doi: 10.1002/ajmg.1320290316. No abstract available.
PubMed 3287925Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989 May;28(2):193-213. doi: 10.1016/0165-1781(89)90047-4.
PubMed 2748771
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical and Molecular Manifestations of Heritable Disorders of Connective Tissue
- ClinicalTrials.gov ID
- NCT00270686
- Acronym / sponsor ID
- 999903330
- Conditions
- Ehlers-Danlos Syndrome, Stickler Syndrome, Marfan Syndrome
- Keywords
- Ehlers-Danlos Syndrome, Stickler Syndrome, Marfan Syndrome, Genetics, Aneurysm
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 929 participants (actual)
- Lead sponsor
- National Institute on Aging (NIA)US National Institutes of Health
- Study start
- 21 Jan 2003
- Study completion
- 2 Jan 2015
- First posted
- 28 Dec 2005 (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.
Background:
- Heritable disorders of connective tissue are genetic conditions that can affect the skin and other parts of the body. They are related to mutations in genes that are responsible for building tissues. The symptoms differ among disorders. Researchers want to study which genes may be responsible for different disorders. They will be performing a long-term (up to 10 years) study and a study that requires a single visit. These studies will look at how these disorders affect the body and what genes may cause these conditions.
Objectives:
- To perform one-time and long-term studies of people who have heritable disorders of connective tissue.
Eligibility:
- Individuals at least 2 years of age who have or may have a heritable disorder of connective tissue.
Design:
- Participants will be screened with a physical exam, medical history, and blood samples.
- Participants will be on one of two parts of this study. The longitudinal arm will require long-term study over about 10 years. The mutational analysis arm will involve a single visit.
- Longitudinal arm participants must be at least 12 years of age. They will have study visits at regular intervals for up to 10 years. The tests given at these visits may include all or some of the following:
- Blood, saliva, urine, and skin samples
- Heart and lung function tests
- Magnetic resonance imaging scans of the neck, chest, spine, and abdomen
- Other imaging studies such as x-rays, bone density scans, and ultrasounds
- Questionnaires about sleep, pain, and quality of life
- Photographs of affected areas.
- Mutational analysis arm participants will have a single study visit. They will provide blood and saliva samples. They will provide tissue from a skin biopsy. They will also let the researchers take photos of any affected body parts. They will complete questionnaires about sleep, pain, and quality of life.
Detailed description
Heritable disorders of connective tissue are a heterogenous group of genetic conditions caused by defects of extracellular matrix elements such as collagen, elastin, mucopolysaccharides or related biomolecules. The genetic cause of many connective tissue disorders has been elucidated, while others are yet to be discovered or further defined. While clinical diagnostic criteria have been established for several of the connective tissue syndromes, many share features that overlap the known descriptions of other connective tissue disorders. Therefore, further characterization and phenotype/genotype correlation is needed to adequately diagnose and find treatments for these yet-to-be genotyped disorders.
An aim of this work is the examination of the cardiovascular, musculoskeletal and neurological complications of heritable connective tissue disorders (HDCT) and the natural history of these complications. Through mutational analysis for genes known to cause the HDCT, as well as identification of new genes, we will assess the relationship between specific mutations and their associated disease phenotypes. Through the analysis of tissue specimens obtained from patients with HDCT, we will identify the biochemical pathways that lead to connective tissue fragility. We will continue to assess the severity, prevalence, and pattern of pain and related psychological and quality of life dimensions in HDCT.
The resulting understanding of genotype/phenotype correlations and biochemical pathways will enhance our understanding of connective tissue biology. This knowledge has the potential to lead to new treatments for not only patients with HDCT, but also for pathological conditions associated with the weakness of connective tissues in aging.
Study design
- Time perspective
- Prospective
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Individuals and their family members will be offered enrollment if they have an established or suspected diagnosis of Marfan, Stickler, or Ehlers-Danlos syndrome, or Overlap connective tissue disorder.
- Determination of eligibility will be made by review of prior records.
- In some cases, a screening evaluation to establish the diagnosis may be performed subjects may be excluded from further participation if the diagnosis is ruled out. Cytogenetic analysis may be necessary to rule out a chromosomal abnormality that has overlapping features with HDCT.
- Clinical inclusion criteria require: personal or family history of one or more of the following features in a pattern suggestive of a heritable connective tissue disorder: Marfanoid body habitus, aortic dilatation and/or dissection, ectopia lentis, detached retina, vitreous degeneration and/or early onset high myopia, posterior cleft palate, joint laxity and/or dislocation, premature osteoarthritis, skin fragility, striae, easy bruising and/or hyperextensibile skin, pectus excavatum or carinatum, scoliosis, spondylolisthesis and/or dural ectasia, Chiari I Malformation, high frequency sensorineural hearing loss, fibromuscular dysplasia of arteries, aneurysms.
Key exclusion criteria (3 listed)
- The only exclusion criterion is inability to provide informed consent, or the absence of a guardian who is authorized to provide informed consent in the case of minor subjects.
- There will be no exclusion based upon age, gender, ethnicity, socioeconomic status, or any other factor except ability to provide informed consent.
- Pregnant and nursing women may be limited in their participation in some aspects of the study (e.g. ionizing radiation exposure or MRI) during the time that they are pregnant or nursing.
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
Description of natural history of Hereditary Disorders of Connective Tissue (HDCT)
Time frame: Ongoing
Genetic analysis to identify novel genes that cause HDCT
Time frame: Ongoing
Biochemical analysis of biospecimens to identify correlations with disease activity and progress
Time frame: Ongoing
Identification of disease treatment targets
Time frame: Ongoing
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 5 Apr 2018.
- Background: PubMed 8425354Ainsworth SR, Aulicino PL. A survey of patients with Ehlers-Danlos syndrome. Clin Orthop Relat Res. 1993 Jan;(286):250-6.
- Background: PubMed 3287925Beighton P, de Paepe A, Danks D, Finidori G, Gedde-Dahl T, Goodman R, Hall JG, Hollister DW, Horton W, McKusick VA, et al. International Nosology of Heritable Disorders of Connective Tissue, Berlin, 1986. Am J Med Genet. 1988 Mar;29(3):581-94. doi: 10.1002/ajmg.1320290316. No abstract available.
- Background: PubMed 2748771Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989 May;28(2):193-213. doi: 10.1016/0165-1781(89)90047-4.
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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.
Nazli B McDonnell, M.D. principal investigator
National Institute on Aging (NIA)
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 Ehlers-Danlos Syndrome and Stickler Syndrome, run by National Institute on Aging (NIA) 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 4 inclusion and 3 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 5 Apr 2018. 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?
Description of natural history of Hereditary Disorders of Connective Tissue (HDCT) (time frame: Ongoing). The study lists 4 primary outcomes in all. 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 NCT00270686, 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 5 Apr 2018.