The Mechanistic Biology of Primary Immunodeficiency Disorders

NCT03394053 | Recruiting

• 2 other identifiers: 18004118-I-0041
• Study Type: observational
• Target: 2,500
• Locations: 1 country
• Sites: 2

Brief Summary

Background: Primary immunodeficiency disorders, or PIDs, are diseases that weaken the immune system. This makes it easier for a person to get sick. Some PIDs are mild and may not be diagnosed until later in life. Other kinds are severe and can be identified shortly after birth. Researchers want to learn more about PIDs by comparing data from relatives and healthy volunteers to people with a PID. Objective: To learn more about PIDs, including their genetic causes. Eligibility: People ages 0-90 with a PID or their healthy biological relatives the same ages Healthy volunteers ages 18-75 Design: Participants will be screened with a medical history, physical exam, and HIV blood test. They may have a pregnancy test. Participants may repeat the screening tests. Blood taken at screening will be used for genetic tests and research tests. Participants will be told test results that affect their health. Some blood will be stored for future research. Adult participants with a PID may have a small piece of skin removed. The area will be numbed. A small tool will take a piece of skin about the size of a pencil eraser. Researchers may collect fluid or tissue samples from PID participants regular medical care. They will use them for research tests. Participants with a PID will have 3 follow-up visits over 10 years (for infants, 2 years). Visits will include a physical exam, medical history, and blood draw. Participants with a PID and their relatives will be called once a year for 10 years. They will talk about how they are feeling and if they have developed any new symptoms or illnesses. ...

Conditions

Primary Immunodeficiency Disorders

Keywords

SCID; Natural Killer (NK) cell deficiency; Combined Immunodeficiency; T-Cell Lymphocytopenia; Of Immune Pathways; Natural History

Outcome Measures

Primary Outcomes (2)

• Identification of unique clinical phenotypes associated with known genetic causes of PID.

  comparing these subjects to the large cohort of data in the Exome Aggregation Consortium (ExAC) Browser (Beta), which is available through http://exact.broadinstitute.org.

  10- 15 years

• Identification of genetic variants that are associated with PID.

  comparing these subjects to the large cohort of data in the Exome Aggregation Consortium (ExAC) Browser (Beta), which is available through http://exact.broadinstitute.org.

  10-15 years

Secondary Outcomes (7)

• Overall survival

  10-15 years

• Incidence of malignancies.

  10-15 years

• Incidence of infections.

  10-15 years

• Incidence of autoimmune disease

  10-15 years

• Incidence of allergic disorders

  10-15 years

Study Arms (3)

Affected Patient

Person with a clinical diagnosis of a PID (age 0-90); either known or unknown as defined by lab and/or clinical findings on 2 or more occasions that are consistent with a defect in innate or adaptive immunity

Normal Volunteer

Persons (age 18-75 years) who are not related to another study subject, who do not have a PID, weight \>110lbs, no history of viral hepatitis B or C, have a negative HIV screening test

Relative of Patient

Biological relatives (age 0-90 years) of a subject who meets affected patient criteria, but who do not have a PID themselves

Eligibility Criteria

• Age: 1 Day - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Potential subjects with confirmed or suspected PID and their biological relatives will be referred to the study from physicians at CNHS or at the NIH. In addition, patients who have a clinical diagnosis of PID may also be referred from physicians at other institutions. Healthy volunteers may be recruited from the NIH Clinical Research Volunteer Program

You may qualify if:

• Subjects must meet one of the following 4 criteria:
• Patients (age 0-90 years) with a clinical diagnosis of a form of PID (either known or unknown). PID is defined by laboratory and/or clinical findings on two or more occasions that are consistent with a defect in innate or adaptive immunity. Specific PIDs are defined by the International Union of Immunological Societies guidelines. These subjects must also be willing to undergo genetic testing and to allow their biospecimens to be modified into iPS cells. Women of childbearing potential, or who are pregnant or lactating, may be eligible. The volume of blood collected for research purposes will be reduced, and no skin biopsies will be performed for research purposes in consideration of their safety.
• Infants identified at birth with positive newborn screening for SCID and confirmed to have T-cell lymphocytopenia. These subjects must be willing to undergo genetic testing.
• Biological relatives (age 0-90 years) of a subject who meets criterion 1a or 1b but who do not have a PID themselves. All relatives must be willing to undergo genetic testing. Women of childbearing potential, or who are pregnant or lactating, may be eligible. The volume of blood collected for research purposes will be reduced in consideration of their safety.
• Healthy volunteers (age 18-75 years) who are not related to another study subject, who do not have a PID, whose weight is greater than 110 pounds, do not have a history of any heart, lung, or kidney disease, or bleeding disorders, do not have a history of viral hepatitis (B or C), and have a negative HIV screening test.
• All subjects must be willing to allow their samples to be stored for future research.

You may not qualify if:

• Subjects with secondary causes of immunodeficiency are excluded from this study. Secondary causes of immunodeficiency include HIV infection and immunodeficiency that is deemed to be secondary to chronic use of immunosuppressive medications or chemotherapeutic agents.
• Any condition that, in the opinion of the investigator, contraindicates participation in this study.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (2)

Children's National Health System (CNHS)

Washington D.C., District of Columbia, 20010, United States

RECRUITING

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Primary Immunodeficiency Diseases

Condition Hierarchy (Ancestors)

Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Luigi D Notarangelo, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Luigi D Notarangelo, M.D.

CONTACT

(301) 761-7550; luigi.notarangelo2@nih.gov

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2018
• First Posted: January 9, 2018
• Study Start: May 30, 2018
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2040
• Last Updated: April 29, 2026

Record last verified: 2026-03-16

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)