Primary Immunodeficiency DisordersNCT03394053
The Mechanistic Biology of Primary Immunodeficiency Disorders
An observational study of Primary Immunodeficiency Disorders, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 day to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Primary Immunodeficiency Disorders
- How many people
- 1,190 participants
- Where
- 2 sitesUnited States
- Study dates
- 30 May 2018to 31 Dec 2040
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 90 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Potential subjects with confirmed or suspected PID and their biological relatives will be referred to the study from physicians 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
Who may be able to join
- 1. Subjects must meet one of the following 3 criteria:
- Patients (age 0-90 years) with a clinical diagnosis of a form of PID (either known or unknown). PID may be 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, however 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.
- Biological relatives (age 0-90 years) of a subject who meet criterion 1a, but who do not have a PID themselves. Relatives may be mother, father, siblings, children, grandparents, aunts, uncles, and first cousins to a patient. There is no limit due to sex, race, or disability. Women of childbearing potential, or who are pregnant or lactating, may be eligible, however the volume of blood collected for research purposes will be reduced in consideration of their safety. Relatives must also be willing to undergo genetic testing.
- Healthy volunteers (age 18-75 years) who are not related to another study subject, do not have a PID, and meet the following:
- Weight greater than 110 pounds.
- Not have any heart, lung, or kidney disease, or bleeding disorders.
Show all 10Show fewer
- Not have a history of viral hepatitis (B or C).
- Not be infected with HIV.
- Not be pregnant.
- 2. All subjects must be willing to allow their samples to be stored for future research.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY8664111010, prpl@cc.nih.gov
- Active, not recruiting
Children's National Health System (CNHS)
Washington D.C., District of Columbia, 20010
About this study
Official title: Investigating the Mechanistic Biology of Primary Immunodeficiency Disorders
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.
Read more
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.
...
Read the detailed description
This is a natural history study designed to investigate forms of primary immunodeficiency disorders (PIDs), and to better define both new and previously described forms of PID, including severe combined immunodeficiency (SCID), combined immunodeficiency, natural killer (NK) cell deficiency, and other disorders. Patients with clinical and/or laboratory evidence of PID will be recruited at the National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID). Subjects with a known or unknown PID will provide one or more blood samples during the course of the study to enable immunologic and genetic investigations of immune pathways contributing to PIDs. These subjects will also be followed clinically to longitudinally assess the natural history of novel and known PIDs.
Subjects will be followed over time with regard to their immunologic phenotype, clinical disease (including incidence of infections, autoimmune phenomena, allergic disease, or malignancies), and response to both preventative and definitive therapies. Biological relatives who do not have PID and healthy adult volunteers will also be eligible to serve as controls for this study.
- Conditions
- Primary Immunodeficiency Disorders
- Keywords
- SCID, Natural Killer (NK) cell deficiency, Combined Immunodeficiency, T-Cell Lymphocytopenia, Of Immune Pathways, Natural History
- Medical subject headings
- Primary Immunodeficiency Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 10-15 years
Secondary outcomes (7)
Overall survival
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.
Measured: 10-15 years
Incidence of malignancies.
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.
Measured: 10-15 years
Incidence of infections.
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.
Measured: 10-15 years
Incidence of autoimmune disease
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.
Measured: 10-15 years
Incidence of allergic disorders
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.
Measured: 10-15 years
Impact of both preventative and definitive treatments on event-free survival (as defined by survival in absence of invasive or chronic infection, autoimmunity, or malignancies).
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.
Measured: 10-15 years
Identification of phenotypic, molecular, and functional abnormalities associated with known or novel forms 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.
Measured: 10-15 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2018
- Study start30 May 2018
- Primary completion31 Dec 2030 (estimated)
- Study completion31 Dec 2040 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Primary Immunodeficiency DisordersStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Family based
- Time perspective
- Prospective
- Enrolment
- 1,190 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Luigi D Notarangelo, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03394053
- Sponsor's protocol ID
- 180041
- Other IDs
- 18-I-0041
- Status last verified
- 28 Oct 2026
- First submitted
- 5 Jan 2018
- Last updated
- 2 Nov 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Marangu-Boore D, Myint-Hpu K, Kang E, Notarangelo LD, Delmonte OM. Bronchiectasis in Inborn Errors of Immunity: Prevalence, Predictors, and Cardiopulmonary Complications in a Genetically Characterized Cohort. J Clin Immunol. 2026 Jul 8. doi: 10.1007/s10875-026-02044-8. Online ahead of print.
PubMed 42414785
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating the Mechanistic Biology of Primary Immunodeficiency Disorders
- ClinicalTrials.gov ID
- NCT03394053
- Acronym / sponsor ID
- 180041
- Conditions
- Primary Immunodeficiency Disorders
- Keywords
- SCID, Natural Killer (NK) cell deficiency, Combined Immunodeficiency, T-Cell Lymphocytopenia, Of Immune Pathways, Natural History
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 1,190 participants (estimated)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 30 May 2018 (actual)
- Primary completion
- 31 Dec 2030 (estimated)
- Study completion
- 31 Dec 2040 (estimated)
- First posted
- 9 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
...
Detailed description
This is a natural history study designed to investigate forms of primary immunodeficiency disorders (PIDs), and to better define both new and previously described forms of PID, including severe combined immunodeficiency (SCID), combined immunodeficiency, natural killer (NK) cell deficiency, and other disorders. Patients with clinical and/or laboratory evidence of PID will be recruited at the National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID). Subjects with a known or unknown PID will provide one or more blood samples during the course of the study to enable immunologic and genetic investigations of immune pathways contributing to PIDs. These subjects will also be followed clinically to longitudinally assess the natural history of novel and known PIDs.
Subjects will be followed over time with regard to their immunologic phenotype, clinical disease (including incidence of infections, autoimmune phenomena, allergic disease, or malignancies), and response to both preventative and definitive therapies. Biological relatives who do not have PID and healthy adult volunteers will also be eligible to serve as controls for this study.
Study design
- Observational model
- Family based
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 1 day to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Potential subjects with confirmed or suspected PID and their biological relatives will be referred to the study from physicians 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
Key inclusion criteria (10 listed)
- Patients (age 0-90 years) with a clinical diagnosis of a form of PID (either known or unknown). PID may be 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, however 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.
- Biological relatives (age 0-90 years) of a subject who meet criterion 1a, but who do not have a PID themselves. Relatives may be mother, father, siblings, children, grandparents, aunts, uncles, and first cousins to a patient. There is no limit due to sex, race, or disability. Women of childbearing potential, or who are pregnant or lactating, may be eligible, however the volume of blood collected for research purposes will be reduced in consideration of their safety. Relatives must also be willing to undergo genetic testing.
- Healthy volunteers (age 18-75 years) who are not related to another study subject, do not have a PID, and meet the following:
- 2. All subjects must be willing to allow their samples to be stored for future research.
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Identification of unique clinical phenotypes associated with known genetic causes of PID.
Time frame: 10- 15 years
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.
Identification of genetic variants that are associated with PID.
Time frame: 10-15 years
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.
7 secondary outcomes
Overall survival
Time frame: 10-15 years
Incidence of malignancies.
Time frame: 10-15 years
Incidence of infections.
Time frame: 10-15 years
Incidence of autoimmune disease
Time frame: 10-15 years
Incidence of allergic disorders
Time frame: 10-15 years
Impact of both preventative and definitive treatments on event-free survival (as defined by survival in absence of invasive or chronic infection, autoimmunity, or malignancies).
Time frame: 10-15 years
Identification of phenotypic, molecular, and functional abnormalities associated with known or novel forms of PID.
Time frame: 10-15 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2026.
- Derived from this study: PubMed 42414785Marangu-Boore D, Myint-Hpu K, Kang E, Notarangelo LD, Delmonte OM. Bronchiectasis in Inborn Errors of Immunity: Prevalence, Predictors, and Cardiopulmonary Complications in a Genetically Characterized Cohort. J Clin Immunol. 2026 Jul 8. doi: 10.1007/s10875-026-02044-8. Online ahead of print.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Luigi D Notarangelo, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Primary Immunodeficiency Disorders, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Luigi D Notarangelo, M.D. ((301) 761-7550, luigi.notarangelo2@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identification of unique clinical phenotypes associated with known genetic causes of PID. (time frame: 10- 15 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03394053, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2026.