A Prospective Natural History Study of Lymphatic Anomalies

Sponsor

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

Overall Status

Recruiting

CT.gov ID

NCT05731141

Collaborator

(none)

1,200

Enrollment

Location

70.1

Anticipated Duration (Months)

17.1

Patients Per Site Per Month

Study Details

Study Description

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. Visits may take up to 8 hours, over 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:

A 6-minute walk test measures physical function.

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphatic Diseases Lymphatic Abnormalities

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

Study Design

Study Type:

Observational

Anticipated Enrollment :

1200 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

A Prospective Natural History Study of Lymphatic Anomalies

Anticipated Study Start Date :

Feb 28, 2023

Anticipated Primary Completion Date :

Dec 31, 2026

Anticipated Study Completion Date :

Dec 31, 2028

Arms and Interventions

Arm	Intervention/Treatment
First Degree Relatives Siblings or parents of patients.
Patients Patients with lymphatic anomalies.

Outcome Measures

Primary Outcome Measures

To establish a longitudinal cohort of participants with lymphatic anomalies [12/31/2028]
We plan to enroll a group of participants willing to participate in the study over time.
To longitudinally determine the age at presentation and incidence of clinical features [12/31/2028]
For each clinical feature or symptoms, the range of ages at the development of that feature/symptom and fraction of participants with that feature

Secondary Outcome Measures

To establish a longitudinal biospecimen repository [12/31/2028]
We plan to collect biospecimens including, but not limited to blood and stool from participants over time.
To determine the best practices for genetic diagnosis based on phenotype [12/31/2028]
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)
To determine the malignant potential of anomalies longitudinally [12/31/2028]
We will track the number of malignancies related to the primary lesion that have developed

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

INCLUSION CRITERIA:

All Groups

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

Stated willingness to comply with required study procedures and availability for the duration of the study
Male or female, aged 0 days and up, including newborns
Ability to understand and speak English
Ability of subject or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document.

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, concomitant medication and allergy review, anthropometrics, and performance status:

Current or history of lymphatic anomaly or symptoms suggestive of a lymphatic disorder
An ill-defined vascular anomaly that is suspected to have an abnormal lymphatic component
A pathogenic, likely pathogenic, or VUS in a genetic disorder with a known lymphatic component
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.
Age 7 or higher and able to sign assent or verbally consent to participation
Be able to comprehend written and verbal English communications.

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:

Individuals who, in the opinion of the investigator, are not able to return for follow-up visits or obtain required follow-up studies. If participants have already completed baseline and/or cross-sectional data before being excluded, their data will still be considered for analysis.
Patients with VUS in genetic disorders without a known abnormal lymphatic feature or a previous lymphatic history.
Patients with genetic disorders without a known abnormal lymphatic feature and a personal history of no lymphatic disease.
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.
Non-English-speaking individuals. Although there are interpreters available at the NIH CC, the LLIS questionnaire does not exist for other languages, notably Spanish, and thus is not validated to measure these parameters in non-English speaking participants.