PI3KCDNCT02257892
Novel Genetic Disorders of the Immune System
An observational study of PI3KCD and CTLA4, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
Background: The immune system helps the body fight infection and disease. People with immune system problems can get infections, blood disorders, and other health problems. Researchers want to learn more about the immune system, like what causes it to not work properly. Read more about this study
- Who is it for?
- Ages 3 to 99 years
- How many people
- 500 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Oct 2014to 30 Aug 2027
- 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 3 to 99 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: No limitations. Generally patients are referring by physicians within the US and Canada
Who may be able to join
- The following inclusion criteria apply to all subjects:
- Patient and relatives aged 0-99 years old to include women who are pregnant or breastfeeding. Only patients >2 years of age, in stable clinical status and meeting the weight requirement of the NIH CC will be physically evaluated at the NIH CC.
- Willingness to allow storage of blood, saliva, and other tissue specimens for future use in medical research.
- Willingness to participate in genetic testing and allow sharing of genetic information in secure databases like dbGAP. These tests may include, but are not limited to, whole exome and whole genome sequencing.
- Priority may be given to individuals with a family history (if readily available) suggestive of multiple affected members with a constellation of signs and symptoms suggestive of immune dysfunction among first- or second-degree relatives.
- Eligibility of special populations
Show all 14Show fewer
- A. NIH employees are eligible
- B. Women who are pregnant or breast feeding are eligible to enroll as probands Pregnant relatives are also eligible for inclusion as
- they can provide important controls, genetic reference and historic clinical information. This protocol is not actively seeking women who are pregnant.
- --C. Pediatric populations are eligible, with restrictions, in order to learn about the natural history of the immune disorders under investigation and to provide diagnostic work up for their ongoing clinical care. Healthy pediatric relatives can provide important diagnostic and genetic reference for affected patients.
- -Pediatric populations are eligible, with restrictions, in order to learn about the natural history of the immune disorders under investigation and to provide diagnostic work up for their ongoing clinical care. Healthy pediatric relatives can provide important diagnostic and genetic reference for affected patients.
- Patients must have:
- An identified genetic basis for an immune disorder or signs and symptoms suggestive of clinically significant immune dysregulation and/or immunodeficiency manifesting with features including but not limited to autoimmunity, autoinflammatory conditions, lymphadenopathy, end-organ dysfunction, unusual infections, allergies, or laboratory abnormalities consistent with immune dysregulation.
- A primary physician outside of the NIH and will be required to submit a letter or clinical summary from their referring physician that documents their relevant health history.
Who cannot join
- Patients will be excluded for any of the following:
- Known genetic disorders that are already well characterized, such as severe combined immunodeficiency (SCID), chronic granulomatous disease (CGD), etc., and those in which we do not have an enduring research interest in the LCIM.
- Patients with unknown immune disorders will be excluded if they have received chemotherapy within the last 6 months for a malignancy or have infections such as HIV or mycobacterial infections.
- Severe clinical illness requiring highly specialized teams and institutions. The NIH may not be able to provide appropriate care for certain referred cases. The Principal Investigator (PI) may determine that the patient is eligible for enrollment but ineligible for admission to the Clinical Center. Patients and relatives with certain obstetric issues may pose a safety risk for travel and evaluation here. Eligibility for this group will be determined on a case by case basis by the PI.
- Patients with well-defined autoimmune conditions such as systemic lupus erythematosus (SLE), Hashimoto s thyroiditis, Addison s disease, Graves disease, sarcoidosis and rheumatoid arthritis, among others.
- Blood relatives will be excluded for the following:
- -Any condition which in the opinion of the investigator may interfere with evaluation of an immune system abnormality that is the subject of study under this protocol.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Background:
- The immune system helps the body fight infection and disease. People with immune system problems can get infections, blood disorders, and other health problems. Researchers want to learn more about the immune system, like what causes it to not work properly.
Read more
Objectives:
- To evaluate people with certain types of immune system disorders.
Eligibility:
- Adults and children with an immune disorder or symptoms of one, and their relatives. Some disorders are not included in this study.
Design:
- Researchers will review participants medical records.
- Participants may mail in a blood or saliva sample, or be evaluated at the clinic. At the clinic, they may have a medical history, physical exam, blood tests, and imaging scans (with dye given through a needle in the arm). They may have genetic testing done on a sample of blood, saliva, hair, or nail clipping.
- Participants may choose to have a skin biopsy. Up to 2 skin samples will be taken from their arm, back, or other area. A biopsy punch is inserted into the skin and rotated. A small circle of skin is removed.
- Participants 10 and older may also choose to have leukapheresis. Blood is taken through a needle in one arm. It passes through a machine that separates the white blood cells. The rest of the blood is returned by needle in the other arm.
- Researchers may recommend medicines, but no treatments are being studied.
- Participants may be invited to return for visits over several years. At those visits, they may repeat some or all of the above tests. Or they may mail in blood or other samples. They may also send medical records.
Read the detailed description
This study is designed to evaluate patients with suspected or identified novel immune disorders, with a focus on abnormal immune homeostasis potentially due to defects in activation or apoptosis. Blood relatives of enrolled patients will also be evaluated. Affected individuals may have Mendelian gene defects involving mostly single or occasionally multiple genes. These patients may have signs and symptoms suggestive of clinically significant lymphocyte homeostasis disorders. However, some selected patients manifesting autoimmunity, autoinflammatory conditions, end-organ dysfunction, Epstein-Barr virus (EBV) and cytomegalovirus (CMV) viremia, frequent infections, allergies, or laboratory abnormalities consistent with immune defects of research interest to the Laboratory of Clinical Immunology and Microbiology may also be studied under this protocol at the discretion of the Investigators.
This protocol will facilitate the discovery of the role of genetic pathways and modes of inheritance associated with pathophysiological events leading to immune system dysregulation, particularly disorders of immune cell homeostasis. A better understanding of the genetics as well as biochemical and molecular basis of complex immune disorders could also lead to the development of novel therapeutic targets and approaches.
Patients will undergo clinical evaluations that include history and physical examinations, blood sampling, radiological exams, genetic testing, skin biopsy, and other medically indicated procedures. Genetically related family members of patients may also be screened and evaluated for clinical, in vitro, and genetic correlates of immune abnormalities. Patients and blood relatives unable or too sick to travel to NIH Clinical Center (CC) may be evaluated through mail-in blood samples. Patients and their relatives will remain enrolled on this study to observe the natural history of the disorder and obtain blood, saliva, skin biopsy, or other specimens at periodic intervals. This study aims to enroll up to a total of 500 patients and their family members.
- Keywords
- CTLA4, PI3KCD, MAGT1, Rare Immune Disorders, Genetic Testing, Natural History
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 |
|---|---|---|
| Patients | Affected patients, with symptoms or genetic mutation | |
| Unaffected/healthy relatives | Relatives without symptoms or genetic mutation |
What is being measured
The primary outcome is the main question the study is designed to answer.
discover novel genes in undiagnosed immune disorders
Determination of a discrete genotype-phenotype association leading to a diagnosis and understanding of the natural history of the patient s immune disorder, an underlying trait, or both.
Measured: ongoing
study the natural history of newly identified genetic disorders
Determination of a discrete genotype-phenotype association leading to a diagnosis and understanding of the natural history of the patient s immune disorder, an underlying trait, or both.
Measured: ongoing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2014 (estimated)
- Study start22 Oct 2014
- Primary completion30 Aug 2027 (estimated)
- Study completion30 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PI3KCDStudies 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
- 500 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- V. Koneti Rao, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02257892
- Sponsor's protocol ID
- 140206
- Other IDs
- 14-I-0206
- Status last verified
- 7 Jan 2026
- First submitted
- 4 Oct 2014
- Last updated
- 26 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Novel Genetic Disorders of the Immune System
- ClinicalTrials.gov ID
- NCT02257892
- Acronym / sponsor ID
- 140206
- Keywords
- CTLA4, PI3KCD, MAGT1, Rare Immune Disorders, Genetic Testing, Natural History
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 22 Oct 2014 (actual)
- Primary completion
- 30 Aug 2027 (estimated)
- Study completion
- 30 Aug 2027 (estimated)
- First posted
- 7 Oct 2014 (estimated)
- 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:
- The immune system helps the body fight infection and disease. People with immune system problems can get infections, blood disorders, and other health problems. Researchers want to learn more about the immune system, like what causes it to not work properly.
Objectives:
- To evaluate people with certain types of immune system disorders.
Eligibility:
- Adults and children with an immune disorder or symptoms of one, and their relatives. Some disorders are not included in this study.
Design:
- Researchers will review participants medical records.
- Participants may mail in a blood or saliva sample, or be evaluated at the clinic. At the clinic, they may have a medical history, physical exam, blood tests, and imaging scans (with dye given through a needle in the arm). They may have genetic testing done on a sample of blood, saliva, hair, or nail clipping.
- Participants may choose to have a skin biopsy. Up to 2 skin samples will be taken from their arm, back, or other area. A biopsy punch is inserted into the skin and rotated. A small circle of skin is removed.
- Participants 10 and older may also choose to have leukapheresis. Blood is taken through a needle in one arm. It passes through a machine that separates the white blood cells. The rest of the blood is returned by needle in the other arm.
- Researchers may recommend medicines, but no treatments are being studied.
- Participants may be invited to return for visits over several years. At those visits, they may repeat some or all of the above tests. Or they may mail in blood or other samples. They may also send medical records.
Detailed description
This study is designed to evaluate patients with suspected or identified novel immune disorders, with a focus on abnormal immune homeostasis potentially due to defects in activation or apoptosis. Blood relatives of enrolled patients will also be evaluated. Affected individuals may have Mendelian gene defects involving mostly single or occasionally multiple genes. These patients may have signs and symptoms suggestive of clinically significant lymphocyte homeostasis disorders. However, some selected patients manifesting autoimmunity, autoinflammatory conditions, end-organ dysfunction, Epstein-Barr virus (EBV) and cytomegalovirus (CMV) viremia, frequent infections, allergies, or laboratory abnormalities consistent with immune defects of research interest to the Laboratory of Clinical Immunology and Microbiology may also be studied under this protocol at the discretion of the Investigators.
This protocol will facilitate the discovery of the role of genetic pathways and modes of inheritance associated with pathophysiological events leading to immune system dysregulation, particularly disorders of immune cell homeostasis. A better understanding of the genetics as well as biochemical and molecular basis of complex immune disorders could also lead to the development of novel therapeutic targets and approaches.
Patients will undergo clinical evaluations that include history and physical examinations, blood sampling, radiological exams, genetic testing, skin biopsy, and other medically indicated procedures. Genetically related family members of patients may also be screened and evaluated for clinical, in vitro, and genetic correlates of immune abnormalities. Patients and blood relatives unable or too sick to travel to NIH Clinical Center (CC) may be evaluated through mail-in blood samples. Patients and their relatives will remain enrolled on this study to observe the natural history of the disorder and obtain blood, saliva, skin biopsy, or other specimens at periodic intervals. This study aims to enroll up to a total of 500 patients and their family members.
Study design
- Observational model
- Family based
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients | – | –Affected patients, with symptoms or genetic mutation |
| Unaffected/healthy relatives | – | –Relatives without symptoms or genetic mutation |
Who may qualify
- Ages
- 3 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- No limitations. Generally patients are referring by physicians within the US and Canada
Key inclusion criteria (14 listed)
- Patient and relatives aged 0-99 years old to include women who are pregnant or breastfeeding. Only patients >2 years of age, in stable clinical status and meeting the weight requirement of the NIH CC will be physically evaluated at the NIH CC.
- Willingness to allow storage of blood, saliva, and other tissue specimens for future use in medical research.
- Willingness to participate in genetic testing and allow sharing of genetic information in secure databases like dbGAP. These tests may include, but are not limited to, whole exome and whole genome sequencing.
- Priority may be given to individuals with a family history (if readily available) suggestive of multiple affected members with a constellation of signs and symptoms suggestive of immune dysfunction among first- or second-degree relatives.
- Eligibility of special populations
Key exclusion criteria (7 listed)
- Known genetic disorders that are already well characterized, such as severe combined immunodeficiency (SCID), chronic granulomatous disease (CGD), etc., and those in which we do not have an enduring research interest in the LCIM.
- Patients with unknown immune disorders will be excluded if they have received chemotherapy within the last 6 months for a malignancy or have infections such as HIV or mycobacterial infections.
- Severe clinical illness requiring highly specialized teams and institutions. The NIH may not be able to provide appropriate care for certain referred cases. The Principal Investigator (PI) may determine that the patient is eligible for enrollment but ineligible for admission to the Clinical Center. Patients and relatives with certain obstetric issues may pose a safety risk for travel and evaluation here. Eligibility for this group will be determined on a case by case basis by the PI.
- Patients with well-defined autoimmune conditions such as systemic lupus erythematosus (SLE), Hashimoto s thyroiditis, Addison s disease, Graves disease, sarcoidosis and rheumatoid arthritis, among others.
- -Any condition which in the opinion of the investigator may interfere with evaluation of an immune system abnormality that is the subject of study under this protocol.
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
discover novel genes in undiagnosed immune disorders
Time frame: ongoing
Determination of a discrete genotype-phenotype association leading to a diagnosis and understanding of the natural history of the patient s immune disorder, an underlying trait, or both.
study the natural history of newly identified genetic disorders
Time frame: ongoing
Determination of a discrete genotype-phenotype association leading to a diagnosis and understanding of the natural history of the patient s immune disorder, an underlying trait, or both.
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 26 Oct 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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.
V. Koneti Rao, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of PI3KCD and CTLA4, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site 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 14 inclusion and 7 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 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 Alanvin D Orpia, R.N. ((240) 550-3663, alanvin.orpia@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
discover novel genes in undiagnosed immune disorders (time frame: ongoing). 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?
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 26 Oct 2026.