NCT05731141

Brief Summary

Background: 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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,200

participants targeted

Target at P75+ for all trials

Timeline
32mo left

Started Mar 2023

Longer than P75 for all trials

Geographic Reach
1 country

2 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress54%
Mar 2023Dec 2028

First Submitted

Initial submission to the registry

February 15, 2023

Completed
1 day until next milestone

First Posted

Study publicly available on registry

February 16, 2023

Completed
1 month until next milestone

Study Start

First participant enrolled

March 20, 2023

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2026

Expected
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2028

Last Updated

April 24, 2026

Status Verified

April 20, 2026

Enrollment Period

3.8 years

First QC Date

February 15, 2023

Last Update Submit

April 23, 2026

Conditions

Keywords

Protein Losing EnteropathyLymphedemaLymphangiectasiaKaposiform LymphangiomatosisGorham Stout DiseaseGeneralized Lymphatic AnomalyComplex Lymphatic AnomalyChylous EffusionChylous AscitesCentral Conducting Lymphatic Anomaly

Outcome Measures

Primary Outcomes (2)

  • To establish a longitudinal cohort of participants with lymphatic anomalies

    We plan to enroll a group of participants willing to participate in the study over time.

    12/31/2028

  • To longitudinally determine the age at presentation and incidence of clinical features

    For each clinical feature or symptoms, the range of ages at the development of that feature/symptom and fraction of participants with that feature

    12/31/2028

Secondary Outcomes (3)

  • To establish a longitudinal biospecimen repository

    12/31/2028

  • To determine the best practices for genetic diagnosis based on phenotype

    12/31/2028

  • To determine the malignant potential of anomalies longitudinally

    12/31/2028

Study Arms (2)

First Degree Relatives

Siblings or parents of patients.

Patients

Patients with lymphatic anomalies.

Eligibility Criteria

Age1 Day - 100 Years
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)
Sampling MethodProbability Sample
Study Population

Patients with lymphatic anomalies and their parents.

You may qualify if:

  • Affected (Proband)
  • 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)
  • 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

You may not qualify if:

  • Affected Proband
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

NOT YET RECRUITING

Related Publications (3)

  • 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.

    PMID: 34166072BACKGROUND
  • 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.

    PMID: 34675250BACKGROUND
  • 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.

    PMID: 35606495BACKGROUND

Related Links

MeSH Terms

Conditions

Lymphatic DiseasesLymphatic AbnormalitiesProtein-Losing EnteropathiesLymphedemaLymphangiectasisOsteolysis, EssentialChylous Ascites

Condition Hierarchy (Ancestors)

Hemic and Lymphatic DiseasesCongenital AbnormalitiesCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesIntestinal DiseasesGastrointestinal DiseasesDigestive System DiseasesBone Diseases, DevelopmentalBone DiseasesMusculoskeletal DiseasesOsteolysisBone ResorptionPeritoneal Diseases

Study Officials

  • Sarah E Sheppard, M.D.

    Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrea I Bowling, C.R.N.P.

CONTACT

Sarah E Sheppard, M.D.

CONTACT

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 15, 2023

First Posted

February 16, 2023

Study Start

March 20, 2023

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2028

Last Updated

April 24, 2026

Record last verified: 2026-04-20

Data Sharing

IPD Sharing
Will share

Investigators will share human data generated in this research for future research as follows:@@@@@@De-identified data in an NIH-funded or approved public repository. @@@@@@De-identified data in another public repository. @@@@@@De-identified data in BTRIS (automatic for activities in the Clinical Center)@@@@@@De-identified or identified data with approved outside collaborators under appropriate agreements.

Shared Documents
CSR
Time Frame
At the time of publication or shortly thereafter.
Access Criteria
Data will be shared through:@@@@@@An NIH-funded or approved public repository: clinicaltrials.gov @@@@@@BTRIS (automatic for activities in the Clinical Center)@@@@@@Approved outside collaborators under appropriate individual agreements.@@@@@@Publication and/or public presentations.@@@@@@This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. As such, this trial will be registered at ClinicalTrials.gov. In addition, every attempt will be made to publish results in peer-reviewed journals. Data from this study may be requested from other researchers after the completion of the primary endpoint by contacting Sarah Sheppard, PI of the study.

Locations