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Protocol Details

A Prospective Natural History Study of Lymphatic Anomalies

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

001084-CH

Sponsoring Institute

National Institute of Child Health and Human Development (NICHD)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: N/A
Max Age: N/A

Referral Letter Required

No

Population Exclusion(s)

None

Keywords

Complex Lymphatic Anomaly;
Central Conducting Lymphatic Anomaly;
Kaposiform Lymphangiomatosis;
Generalized Lymphatic Anomaly;
Gorham Stout Disease;
Lymphedema;
Chylous Effusion;
Chylous Ascites;
Protein Losing Enteropathy;
Lymphangiectasia;
Natural History

Recruitment Keyword(s)

None

Condition(s)

Lymphatic Diseases;
Lymphatic Abnormalities

Investigational Drug(s)

None

Investigational Device(s)

None

Intervention(s)

None

Supporting Site

National Institute of Child Health and Human Development

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 are many things 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 how 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 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 each, over 2-5 days. These visits may also be completed via telemedicine.

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.

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Eligibility

INCLUSION CRITERIA:

All Groups

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

1. Stated willingness to comply with required study procedures and availability for the duration of the study

2. Male or female, aged 0 days and up, including newborns

3. Ability to understand and speak English

4. 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:

1. Current or history of lymphatic anomaly or symptoms suggestive of a lymphatic disorder

2. An ill-defined vascular anomaly that is suspected to have an abnormal lymphatic component

3. A pathogenic, likely pathogenic, or VUS in a genetic disorder with a known lymphatic component

4. 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:

1. A first-degree family member of an affected participants.

2. Age 7 or higher and able to sign assent or verbally consent to participation

3. 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:

1. 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.

2. Patients with VUS in genetic disorders without a known abnormal lymphatic feature or a previous lymphatic history.

3. Patients with genetic disorders without a known abnormal lymphatic feature and a personal history of no lymphatic disease.

4. 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.

5. 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.


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Citations:

M(SqrRoot) kinen 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: 34166072.

Brouillard P, Witte MH, Erickson RP, Damstra RJ, Becker C, Qu(SqrRoot)(Copyright)r(SqrRoot)(Copyright) I, Vikkula M. Primary lymphoedema. Nat Rev Dis Primers. 2021 Oct 21;7(1):77. doi: 10.1038/s41572-021-00309-7. PMID: 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. Erratum in: Eur J Hum Genet. 2022 Jun 3;: PMID: 35606495; PMCID: PMC9436962.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Sarah E. Sheppard, M.D.
National Institute of Child Health and Human Development (NICHD)
NIHBC 10 - CRC BG RM 2-5130
10 CENTER DR
BETHESDA MD 20892
(240) 578-5047
sarah.sheppard@nih.gov

Andrea I. Bowling, C.R.N.P.
National Institute of Child Health and Human Development (NICHD)
NIHBC 10 - CRC BG RM 2-5152
10 CENTER DR
BETHESDA MD 20892
(301) 451-3824
andrea.bowling@nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: TTY Users Dial 7-1-1
ccopr@nih.gov

Clinical Trials Number:

NCT05731141

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