Abnormal ElastogenesisNCT04664478
Gene First Approach to Connective Tissue Disease
An observational study of Abnormal Elastogenesis and Vascular Diseases, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
Background: Elastic fibers affect parts of the body that stretch repetitively, such as the skin, blood vessels, and lungs. Researchers want to use medical and research tests in patients with already identified changes in a set of connective tissue genes to better understand diseases related to elastic fibers. Read more about this study
- Who is it for?
- Ages 2 to 100 years
- Conditions the study is for
- Abnormal Elastogenesis, Vascular Diseases, Connective Tissue Diseases
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Apr 2021to 29 Aug 2025
- 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 to 100 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients with variation in our genes of interest(relevant genotypes) to identify relevant phenotypes in the cohort via deep phenotyping.
Who may be able to join
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Participant must have a genetic variant in one of the connective tissue target genes identified on previous research or clinical genetic testing. A clinical or research report of the variant in question will be reviewed at the time of referral.
- This variant must be of sufficient interest for focused study to the clinical research team. Interest may be based on a variety of factors including: its population frequency, potential pathogenicity, or apparent genotype/phenotype associations in the medical record, among others.
- Male or female, within the ages of 2 and 100 years old.
Who cannot join
- 1. Pregnancy or Nursing.
- Rationale for excluding pregnant women
- We do believe that pregnancy likely impacts connective tissue disease and deserves focused study. Unfortunately, we do not believe that our current study design will allow us to attract a large enough number of currently pregnant women to adequately power a direct study into the impacts of connective tissue disease on pregnancy. And the single visit nature of the study precludes following an individual throughout their pregnancy. As such, we have chosen to exclude currently pregnant women from the study. We do, however, welcome their participation once pregnancy is done. We expect that our history taking will include questions about pregnancy and so may still collect historical data related to these variants and pregnancy.
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: Natural History Study: Gene First Approach to Connective Tissue Disease
Background:
Elastic fibers affect parts of the body that stretch repetitively, such as the skin, blood vessels, and lungs. Researchers want to use medical and research tests in patients with already identified changes in a set of connective tissue genes to better understand diseases related to elastic fibers.
Read more
Objective:
To learn more about the impact of underlying changes in a set of connective tissue genes on people s overall health.
Eligibility:
People ages 2-100 who have had a gene test that identified a change in a gene that affects elastic fibers. Initial emphasis will be placed on people with changes in ELN, LOX, MFAP4, FBLN5 and EFEMP2.
Design:
Participants will visit the NIH for several days to perform tests that will help researchers learn more about how changes in connective tissue genes affect a person s health. They will also have clinicians take their medical history and physical exam. Optional tests include giving blood samples, hair strand, urine, and/or saliva samples. They may have a cheek swab or skin biopsy. Their genes may be studied. Their cells may be grown in a laboratory. Participants may have photographs taken of the face and body.
They will receive exams by a medical team with experience in connective tissue disease. They may have a dental exam or eye exams and with photography. During the eye exam, pictures may be taken of the blood vessels in the eyes. If this occurs, they will get dye through an intravenous (IV) line in an arm vein.
They will also have medical tests to check the health of tissues that may be affected by these connective tissue genes. Participants may have lung function tests. They may have a six-minute walk test. They may complete a treadmill or bike stress test. Their heart s electrical activity may be recorded. Participants may have X-rays and ultrasounds. They may have a DEXA scan to measure bone density. They may have CT, MRI or other imaging scans. Some of these tests require the participant to get a contrast fluid via IV.
Participants may have a skin elasticity test using a suction cup that pulls lightly on their skin.
Participants may wear blood pressure cuffs while probes are placed on their skin. The tests will be chosen for each individual based on their specific gene change and no person is expected to complete all tests. Participation will last 3-5 days.
Read the detailed description
Study Description:
This protocol will allow deep phenotyping of patients with underlying gene variation in a set of connective tissue genes (see Appendix A for list) to both quantify risk of specific disease features and to describe novel phenotypes attributable to gene variation.
Study Objectives:
Primary Objective: Phenotypic description for patients with known variation in specified connective tissue genes.
Secondary Objective: Within and across gene correlation of variant type with specific phenotype outcomes.
Endpoints:
Primary Endpoint: We will quantify the frequency of a set phenotypic observations for patients with variation in specified connective tissue genes. Organ systems under evaluation are those predicted to be affected based on gene expression or previous medical record investigations by our collaborators at Geisinger Health System.
Secondary Endpoint: We will compare the frequency of specified phenotypes within genes in patients with specific genotypes and across connective tissue genes. Different variation type (stop gain vs missense) or location (in or out of a functional domain) has the potential to cause different phenotypic outcomes. Likewise, variation in genes impacting the same pathways may have overlapping phenotypes/outcomes.
- Keywords
- elastic fiber, gene variation, Phenotyping, genotype-phenotype correlations, elastin, Natural History
- Medical subject headings
- Vascular Diseases, Connective Tissue Diseases, Aortic Stenosis, Supravalvular
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 |
|---|---|---|
| Subjects with abnormal elastogenesis | Participants with genetic variant in the connective tissue target genes |
What is being measured
The primary outcome is the main question the study is designed to answer.
The frequency of a set phenotypic observations
The frequency of a set phenotypic observations for patients with variation in specified connective tissue genes.
Measured: 2 months
Secondary outcomes (1)
The frequency of specified phenotypes within genes in patients with specific genotypes and across connective tissue genes
We will compare the frequency of specified phenotypes within genes in patients with specific genotypes and across connective tissue genes. Different variation type (stopgain vs missense) or location (in or out of a functional domain) has the potential to cause different phenotypic outcomes. Likewise, variation in genes impacting the same pathways may have overlapping phenotypes/outcomes.
Measured: 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2020
- Study start22 Apr 2021
- Primary completion29 Aug 2025
- Study completion29 Aug 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Abnormal ElastogenesisStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Manfred Boehm, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04664478
- Sponsor's protocol ID
- 200158
- Other IDs
- 20-H-0158
- Status last verified
- 5 Aug 2026
- First submitted
- 10 Dec 2020
- Last updated
- 7 Aug 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: It is not yet known.
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Natural History Study: Gene First Approach to Connective Tissue Disease
- ClinicalTrials.gov ID
- NCT04664478
- Acronym / sponsor ID
- 200158
- Keywords
- elastic fiber, gene variation, Phenotyping, genotype-phenotype correlations, elastin, Natural History
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 22 Apr 2021 (actual)
- Primary completion
- 29 Aug 2025 (actual)
- Study completion
- 29 Aug 2025 (actual)
- First posted
- 11 Dec 2020 (actual)
- 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:
Elastic fibers affect parts of the body that stretch repetitively, such as the skin, blood vessels, and lungs. Researchers want to use medical and research tests in patients with already identified changes in a set of connective tissue genes to better understand diseases related to elastic fibers.
Objective:
To learn more about the impact of underlying changes in a set of connective tissue genes on people s overall health.
Eligibility:
People ages 2-100 who have had a gene test that identified a change in a gene that affects elastic fibers. Initial emphasis will be placed on people with changes in ELN, LOX, MFAP4, FBLN5 and EFEMP2.
Design:
Participants will visit the NIH for several days to perform tests that will help researchers learn more about how changes in connective tissue genes affect a person s health. They will also have clinicians take their medical history and physical exam. Optional tests include giving blood samples, hair strand, urine, and/or saliva samples. They may have a cheek swab or skin biopsy. Their genes may be studied. Their cells may be grown in a laboratory. Participants may have photographs taken of the face and body.
They will receive exams by a medical team with experience in connective tissue disease. They may have a dental exam or eye exams and with photography. During the eye exam, pictures may be taken of the blood vessels in the eyes. If this occurs, they will get dye through an intravenous (IV) line in an arm vein.
They will also have medical tests to check the health of tissues that may be affected by these connective tissue genes. Participants may have lung function tests. They may have a six-minute walk test. They may complete a treadmill or bike stress test. Their heart s electrical activity may be recorded. Participants may have X-rays and ultrasounds. They may have a DEXA scan to measure bone density. They may have CT, MRI or other imaging scans. Some of these tests require the participant to get a contrast fluid via IV.
Participants may have a skin elasticity test using a suction cup that pulls lightly on their skin.
Participants may wear blood pressure cuffs while probes are placed on their skin. The tests will be chosen for each individual based on their specific gene change and no person is expected to complete all tests. Participation will last 3-5 days.
Detailed description
Study Description:
This protocol will allow deep phenotyping of patients with underlying gene variation in a set of connective tissue genes (see Appendix A for list) to both quantify risk of specific disease features and to describe novel phenotypes attributable to gene variation.
Study Objectives:
Primary Objective: Phenotypic description for patients with known variation in specified connective tissue genes.
Secondary Objective: Within and across gene correlation of variant type with specific phenotype outcomes.
Endpoints:
Primary Endpoint: We will quantify the frequency of a set phenotypic observations for patients with variation in specified connective tissue genes. Organ systems under evaluation are those predicted to be affected based on gene expression or previous medical record investigations by our collaborators at Geisinger Health System.
Secondary Endpoint: We will compare the frequency of specified phenotypes within genes in patients with specific genotypes and across connective tissue genes. Different variation type (stop gain vs missense) or location (in or out of a functional domain) has the potential to cause different phenotypic outcomes. Likewise, variation in genes impacting the same pathways may have overlapping phenotypes/outcomes.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Subjects with abnormal elastogenesis | – | –Participants with genetic variant in the connective tissue target genes |
Who may qualify
- Ages
- 2 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients with variation in our genes of interest(relevant genotypes) to identify relevant phenotypes in the cohort via deep phenotyping.
Key inclusion criteria (4 listed)
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Participant must have a genetic variant in one of the connective tissue target genes identified on previous research or clinical genetic testing. A clinical or research report of the variant in question will be reviewed at the time of referral.
- This variant must be of sufficient interest for focused study to the clinical research team. Interest may be based on a variety of factors including: its population frequency, potential pathogenicity, or apparent genotype/phenotype associations in the medical record, among others.
- Male or female, within the ages of 2 and 100 years old.
Key exclusion criteria (3 listed)
- 1. Pregnancy or Nursing.
- Rationale for excluding pregnant women
- We do believe that pregnancy likely impacts connective tissue disease and deserves focused study. Unfortunately, we do not believe that our current study design will allow us to attract a large enough number of currently pregnant women to adequately power a direct study into the impacts of connective tissue disease on pregnancy. And the single visit nature of the study precludes following an individual throughout their pregnancy. As such, we have chosen to exclude currently pregnant women from the study. We do, however, welcome their participation once pregnancy is done. We expect that our history taking will include questions about pregnancy and so may still collect historical data related to these variants and pregnancy.
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
The frequency of a set phenotypic observations
Time frame: 2 months
The frequency of a set phenotypic observations for patients with variation in specified connective tissue genes.
1 secondary outcome
The frequency of specified phenotypes within genes in patients with specific genotypes and across connective tissue genes
Time frame: 2 months
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 7 Aug 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. It is not yet known.
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.
Manfred Boehm, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
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 Abnormal Elastogenesis and Vascular Diseases, run by National Heart, Lung, and Blood Institute (NHLBI) 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 7 Aug 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?
The frequency of a set phenotypic observations (time frame: 2 months). 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 7 Aug 2026.