ClinicalTrials.gg
RecruitingNCT05731141Updated Oct 23, 2026

A Prospective Natural History Study of Lymphatic Anomalies

An observational study in Lymphatic Diseases and Lymphatic Abnormalities, sponsored by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Recruiting at 2 sites in United States. Open to participants aged 1 Day to 100 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-10-23.

Primary conditionLymphatic AbnormalitiesRegistry: Lymphatic DiseasesReclassifiedWhy we changed it
Registry
Lymphatic Diseases — the first condition term the registry derived for this study.
ClinicalTrials.gg
Lymphatic Abnormalities
Why
  1. The study's listed conditions name Lymphatic Abnormalities, a narrower term within Lymphatic Diseases.
Confidence
High: the new condition is named in the study's own listed conditions. Of 351 hand-checked studies reclassified this way, 68% were exactly right and 84% in the right disease family; the registry's first term was right for 5% (measured 2026-10-21). How we classify →
Wrong?
Tell us the study's main condition →

Sponsored by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) · Observational

From the registry’s dates

  • Started Mar 2023; still recruiting 3 years 7 months later.
Updated Oct 21, 2026Primary completion movedGo to Updates ↓
Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
1,200
Ages
1 Day to 100 Years
Sex
All
01

Study 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.

Read the detailed description

Study Description:

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
02

Conditions studied

  • Lymphatic Diseases
  • Lymphatic Abnormalities

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Keywords

  • Protein Losing Enteropathy
  • Lymphedema
  • Lymphangiectasia
  • Kaposiform Lymphangiomatosis
  • Gorham Stout Disease
  • Generalized Lymphatic Anomaly
  • Complex Lymphatic Anomaly
  • Chylous Effusion
  • Chylous Ascites
  • Central Conducting Lymphatic Anomaly
03

In context

Lymphatic Abnormalities Reclassified

42 studies on the registry are indexed under Lymphatic Abnormalities; 17 are open to participants now.

This study's planned enrollment of 1,200 is above the median of 56 across 13 observational studies indexed under Lymphatic Abnormalities.

Browse Lymphatic Abnormalities studies →

Lead sponsor

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is the lead sponsor of 422 studies on the registry; 24 are open to participants now.

Of its 14 completed or terminated interventional studies of FDA-regulated products, 11 (79%) have results posted.

Compared within Lymphatic Abnormalities, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Lymphatic Diseases. The counts are of registry records indexed under each term, refreshed daily. How we classify →

04

Who can participate

Ages eligible
1 Day to 100 Years
Sexes eligible
All
Accepts healthy volunteers
Yes
Sampling method
Probability sample

Study population

Patients with lymphatic anomalies and their parents.

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

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)

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

EXCLUSION CRITERIA:

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.

05

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
1,200 participants (estimated)

Groups and cohorts

  • First Degree Relatives

    Siblings or parents of patients.

  • Patients

    Patients with lymphatic anomalies.

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 12/31/2028

  2. 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

    Time frame: 12/31/2028

Secondary outcomes

  1. To establish a longitudinal biospecimen repository

    We plan to collect biospecimens including, but not limited to blood and stool from participants over time.

    Time frame: 12/31/2028

  2. To determine the best practices for genetic diagnosis based on phenotype

    We will analyze diagnostic yields by phenotype (how many participants are able to have a genetic diagnosis in proportion to the number of participants who receive genetic testing) and genetic test methodology (to determine which genetic test is most helpful in diagnosing lymphatic anomalies)

    Time frame: 12/31/2028

  3. To determine the malignant potential of anomalies longitudinally

    We will track the number of malignancies related to the primary lesion that have developed

    Time frame: 12/31/2028

07

Study locations

1 of 2 sites recruiting
  • National Institutes of Health Clinical Center
    Bethesda, Maryland 20892, United States
    Recruiting
    • NIH Clinical Center Office of Patient Recruitment (OPR) · Contactccopr@nih.gov · 800-411-1222
  • Children's Hospital of Philadelphia
    Philadelphia, Pennsylvania 19104, United States
    Not yet recruiting
08

References and documents

Publications

  • 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. PubMed 34166072 ↗
  • 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. PubMed 34675250 ↗
  • 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. PubMed 35606495 ↗

Individual participant data

Plan to share: Yes — 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.

Supporting information: Clinical study report

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.

09

Timeline

3 registry updates since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedDate before it movedWhere the date was before it moved

Started Mar 2023 (actual). Primary completion is estimated for Dec 2028, 69 months after the start.

Primary completion moved once since we started tracking on Sep 25, 2026: Dec 2026 → Dec 2028, on Oct 21, 2026.

Earlier changes are on the record history on ClinicalTrials.gov ↗

How these figures are worked out, and which studies are left out of them.

Registered
Feb 15, 2023
First posted
Feb 16, 2023
StartActual
Mar 20, 2023
Primary completionEst.
Dec 31, 2028was Dec 2026
CompletionEst.
Dec 31, 2028
Last update
Oct 23, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
Primary completion
Dec 31, 2026→Dec 31, 2028
Oct 21, 2026
Site contacts
Changed at 1 site. See the sites
Show the site
  • Children's Hospital of Philadelphia · Philadelphia, United StatesContact d•••@chop.edu · •••1033→S•••@chop.edu · •••2482
Oct 21, 2026
Show all 3 updates
  1. Oct 23, 2026
    Minor edits only
    + 1 other change: verification date
  2. Oct 21, 2026
    Primary completion Dec 31, 2026→Dec 31, 2028
    Site contacts Changed at 1 site. See the sites
    Show the site
    • Children's Hospital of Philadelphia · Philadelphia, United StatesContact d•••@chop.edu · •••1033→S•••@chop.edu · •••2482
    + 1 other change: verification date
  3. Sep 28, 2026
    Minor edits only
    + 1 other change: verification date

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT05731141
Responsible party
Sponsor
First posted
Feb 16, 2023
Start date
Mar 20, 2023
Primary completion
Dec 31, 2028 (estimated)
Completion
Dec 31, 2028 (estimated)
Last update
Oct 23, 2026

Study contacts

Andrea I Bowling, C.R.N.P.
Contact
nichd_lymphaticanoma@mail.nih.gov
(301) 451-3824
Sarah E Sheppard, M.D.
Contact
sarah.sheppard@nih.gov
(240) 578-5047
Sarah E Sheppard, M.D.
principal investigator · Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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