A Prospective Natural History Study of Lymphatic Anomalies
NCT ID: NCT05731141
Last Updated: 2025-11-12
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
1200 participants
OBSERVATIONAL
2023-03-20
2028-12-31
Brief Summary
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The lymphatic system is a network of vessels that carry a clear fluid called lymph through the body. Problems in the lymphatic system can cause pain, fluid buildup, and issues with immunity. There is much researchers do not understand about lymphatic anomalies. In this natural history study, they will collect data from a lot of people over a long time.
Objective:
To better understand why lymphatic anomalies develop. The goal is to improve future treatments.
Eligibility:
People aged 0 days and older with a suspected or confirmed lymphatic anomaly. Their unaffected parents or siblings aged 7 years or older are also needed.
Design:
Participants may remain in the study indefinitely. Affected participants may be evaluated every 10 months to 2 years. Some participants will be seen over telemedicine. Others will be seen at the NIH Clinical Center for 2-5 days.
All participants will have a physical exam. They may provide specimens including blood, saliva, hair follicles, stool, skin, and other tissues. Samples may be used for genetic testing.
Participants may undergo other tests depending on their medical conditions. The NIH Clinical Center visit may include:
Heart tests include placing stickers on the chest to measure electrical activity and using sound waves to capture pictures of the heart.
A lung test measures the muscle strength in the chest. Participants will blow into a tube.
Photographs may be taken of participants faces and other features.
Imaging scans will take pictures of the inside of the body. One scan will measure bone density.
One type of scan tracks how lymph fluid moves through the body. Participants will be under anesthesia, and they will be injected with a dye.
Detailed Description
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A natural history study for lymphatic anomalies to systematically evaluate the disease phenotypes and long-term outcomes to provide improved prognostication to families, establish screening/monitoring guidelines, determine best practices for genetic diagnosis, explore family opinions, and explore fertility for those on long term medication management. This study will allow us to identify novel end points for future clinical trials.
Objectives:
Primary objectives:
* To establish a longitudinal cohort of participants with lymphatic anomalies
* To longitudinally determine the age at presentation and incidence of clinical features
Secondary objectives:
* To establish a longitudinal biospecimen repository
* To determine the best practices for genetic diagnosis based on phenotype.
* To determine the malignant potential of anomalies longitudinally
Endpoints:
Primary endpoints:
* The number of participants with lymphatic anomalies
* For each clinical feature or symptoms, the range of ages at the development of that feature/symptom and fraction of participants with that feature
* Quantification and identification of novel features associated with disease.
Secondary endpoints:
* The number of specimens collected
* Diagnostic yields by phenotype and genetic test methodology
* Number of malignancies related to the primary lesion that have developed
Conditions
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Keywords
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Study Design
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COHORT
PROSPECTIVE
Study Groups
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First Degree Relatives
Siblings or parents of patients.
No interventions assigned to this group
Patients
Patients with lymphatic anomalies.
No interventions assigned to this group
Eligibility Criteria
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Inclusion Criteria
In order to be eligible to participate in this study, an individual must meet one of the following criteria as determined after review of medical history:
* Current or history of lymphatic anomaly or symptoms suggestive of a lymphatic disorder Or
* An ill-defined vascular anomaly that is suspected to have an abnormal lymphatic component Or
* A pathogenic, likely pathogenic, or VUS in a genetic disorder with a known lymphatic component Or
* Clinical diagnosis of a syndrome with a known lymphatic component
Unaffected (First Degree Relatives: Parents and Siblings)
Genetic variants underlying complex lymphatic anomalies can be passed down through parents or be new in a child (de novo). Inclusion of first-degree relatives will assist in genetic analysis to delineate whether the variant is inherited or de novo.
To be eligible to participate as a first degree relative in this study, an individual must be a first-degree family member of an affected participants
Exclusion Criteria
An individual who meets any of the following criteria will be excluded from participation in this study after review of medical history, concomitant medication and allergy review, anthropometrics, and performance status:
-Any condition, in the opinion of the investigator, that would increase risk of participation or impair their ability to comply with protocol requirements.
Lymphatic anomalies that are definitively determined to be secondary by the principal investigator will be excluded from this study. For example, participants who develop a lymphedema after breast cancer surgery.
Unaffected (First Degree Relatives)
-Any condition, in the opinion of the investigator, that would increase risk of participation or impair their ability to comply with protocol requirements.
1 Day
100 Years
ALL
Yes
Sponsors
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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
NIH
Responsible Party
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Principal Investigators
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Sarah E Sheppard, M.D.
Role: PRINCIPAL_INVESTIGATOR
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Locations
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National Institutes of Health Clinical Center
Bethesda, Maryland, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Countries
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Central Contacts
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Facility Contacts
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NIH Clinical Center Office of Patient Recruitment (OPR)
Role: primary
Yoav Dori
Role: primary
References
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Makinen T, Boon LM, Vikkula M, Alitalo K. Lymphatic Malformations: Genetics, Mechanisms and Therapeutic Strategies. Circ Res. 2021 Jun 25;129(1):136-154. doi: 10.1161/CIRCRESAHA.121.318142. Epub 2021 Jun 24.
Brouillard P, Witte MH, Erickson RP, Damstra RJ, Becker C, Quere I, Vikkula M. Primary lymphoedema. Nat Rev Dis Primers. 2021 Oct 21;7(1):77. doi: 10.1038/s41572-021-00309-7.
Liu M, Smith CL, Biko DM, Li D, Pinto E, O'Connor N, Skraban C, Zackai EH, Hakonarson H, Dori Y, Sheppard SE. Genetics etiologies and genotype phenotype correlations in a cohort of individuals with central conducting lymphatic anomaly. Eur J Hum Genet. 2022 Sep;30(9):1022-1028. doi: 10.1038/s41431-022-01123-9. Epub 2022 May 24.
Related Links
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NIH Clinical Center Detailed Web Page
Other Identifiers
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001084-CH
Identifier Type: -
Identifier Source: secondary_id
10001084
Identifier Type: -
Identifier Source: org_study_id