XLANCT00001244
Immune Regulation in Patients With Common Variable Immunodeficiency and Related Inborn Errors of Immunity (IEI)
An observational study of XLA and CVID, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
This study aims to understand the causes and progression of Common Variable Immunodeficiency (CVID) and related inborn errors of immunity (IEI). These are conditions where the immune system does not function properly, leading to frequent infections and other complications such as gastrointestinal inflammation, lung… Read more about this study
- Who is it for?
- Ages 2 to 120 years
- Conditions the study is for
- XLA, CVID, Yao Syndrome
- How many people
- 500 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jan 1990to not given
- 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 2 to 120 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: General population - Physician referral required
Who may be able to join
- Must have a verifiable diagnosis of common variable immune deficiency as defined by a decrease both in IgG and at least one other Ig isotype to below two standard deviations of normal control levels OR B-cell immunodeficiencies related to CVI (defined as selective IgA deficiency, selective IgG isotype deficiency, agammaglobulinemia, and hypogammaglobulinemia associated with Epstein-Barr virus infection), or hypogammaglobulinemia associated with other related inborn errors of immunity. This includes patients with a defined diagnosis of Blau or Yao Syndrome.
- Must be 2 years old or greater.
- Patients with repeated infections and suspected of having an inborn error of immunity.
- Patients must be referred by their primary medical care provider.
- On investigator s discretion, unaffected family members (mother, father, siblings, children, grandparents, aunts, uncles, and first cousins) may be asked for the provision of blood or buccal specimens for research purposes.
- Patients who are lactating, may be eligible and will only undergo tests and procedures, and/or receive medications for which data exists that proves that they are minimal risk to the child.
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- Pregnant women will not be newly enrolled onto this protocol, however existing patients who become pregnant while on study will remain on study, as literature about pregnancy in CVI patients is sparse and outside providers have minimal knowledge about managing CVI during pregnancy. Pregnant women will only undergo tests and procedures, and/or receive medications for which data exists that proves that they are minimal risk to the fetus. Pregnant unaffected relatives will not be enrolled in this study).
- All patients must be willing to have research samples stored for future studies and/or other research purposes.
- NIH staff and family members of study team members may be enrolled in this study as this population may meet study criteria. Neither participation nor refusal to participate as a subject in the research will have an effect, either beneficial or adverse, on the participant s employment or position at the NIH. Every effort will be made to protect participant information, but such information may be available in medical records and may be available to authorized users outside of the study team in both an identifiable and unidentifiable manner. The NIH investigator will provide and request that the NIH staff member review the Frequently Asked Questions (FAQs) for Staff Who are Considering Participating in NIH Research and the Leavy Policy for NIH Employees Participating in NIH Medical Research Studies (NIH Policy Manual 2300-630-3).
Who cannot join
- Presence of other medical illnesses that would preclude individuals from undergoing routine diagnostic testing or testing for immunologic features of immunodeficiency.
- Presence of a condition or treatment, such as HIV, cytotoxic chemotherapy or malignancy, that in the investigator s opinion could interfere with evaluation of the condition under study.
- Pregnancy at the time of enrollment.
- Inability of an adult participant to provide informed consent for themselves (decisionally impaired adult).
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
Ivan Fuss, M.D., 301-761-7091, ifuss@niaid.nih.gov
About this study
Official title: Studies of Immune Regulation in Patients With Common Variable Immunodeficiency and Related Inborn Errors of Immunity (IEI)
This study aims to understand the causes and progression of Common Variable Immunodeficiency (CVID) and related inborn errors of immunity (IEI). These are conditions where the immune system does not function properly, leading to frequent infections and other complications such as gastrointestinal inflammation, lung and liver disease, autoimmune conditions, and an increased risk of certain cancers. By studying patients with CVI and related immune disorders, we hope to develop better ways to diagnose, treat, and prevent complications associated with these conditions.
Patients diagnosed with CVID or related immune disorders must be referred by their physician and medical records reviewed by the study team to confirm eligibility to participate in this study. Once enrolled, participants will undergo various tests, including blood draws, physical exams, and imaging studies like CT scans to track changes over time. We may collect samples such as blood, urine, stool, or saliva for research purposes. If a surgical procedure or biopsy is performed because it is medically necessary, we may collect an additional sample for research testing. Family members of patients may be asked to provide blood samples for comparison. Some tests may be done remotely if participants or family members cannot travel to the study site.
Read more
Who Can Participate
- Patients diagnosed with CVI or related IEI, such as X-linked agammaglobulinemia, Blau Syndrome or Yao Syndrome.
- Participants must be at least 2 years old.
- Family members of patients may include parents, siblings, grandparents, children, aunts, uncles, and cousins.
- Pregnant women already enrolled in the study will continue to participate, but new pregnant participants will not be enrolled.
Potential Risks and Benefits
- Risks: Blood draws may cause discomfort, bruising, or infection. Apheresis may cause dizziness, nausea, or muscle cramps; this procedure is to collect specific cells in the blood and is infrequently done on this protocol. Extra biopsies during clinically indicated procedures may increase the risk of complications; they will only be collected after the medically necessary biopsies are taken and if it is safe to collect any extra biopsies.
- Benefits: Participants may not receive direct medical benefits, but the study will contribute to a better understanding of CVID and related conditions, potentially leading to improved treatments.
Read the detailed description
The purpose of this protocol is to carry out laboratory studies concerning the immunopathogenesis of Common Variable Immunodeficiency (CVI) and related inborn errors of immunity (IEI). Additionally, we aim to document and track the progression of known complications of these immune abnormalities. Complications associated with CVI include recurrent respiratory, granulomas, pulmonary insufficiency, gastrointestinal bacterial infections, enteropathy, nodular regenerative hyperplasia, lymphoid malignancy, and various autoimmune manifestations.
Patients with CVI and related IEI will be enrolled into this natural history study. Protocol procedures will include baseline measurements of and changes in lab studies. First- or second-degree genetically related family members (limited to mother, father, siblings, grandparents, children, aunts, uncles, and first cousins of an affected patient) may also be screened for clinical, in vitro, and genetic correlates of immune abnormalities. Changes in the patients' clinical state will be measured to determine the precursors of disease complications. This may lead to developments in improving preventive measures and novel treatment options for this population.
- Conditions
- XLA, CVID, Yao Syndrome, Blau Syndrome
- Keywords
- Blau Syndrome, XLA, Humoral Immunodeficiency, CVID enteropathy, CVID, Agammaglobulinemia, Inborn Errors of Immunity, Yao Syndrome
- Medical subject headings
- Blau syndrome, Agammaglobulinemia
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 |
|---|---|---|
| General Population | Physician referral required |
What is being measured
The primary outcome is the main question the study is designed to answer.
Establish pattern/pace of disease process
To establish the pattern and pace of change of disease (frequency, distribution, type and extent of infections, inflammatory lesions and abnormalities of immune function).
Measured: At 1 year and ongoing
Evaluation of organ dysfunction/damage resulting from immune abnormality
To establish the extent of organ involvement (infection and/or inflammation) and organ damage or dysfunction resulting from the abnormality of immune function.
Measured: Ongoing
Characterization of immune abnormalities
To characterize the physiologic, biochemical or genetic basis of theabnormality of immunity.
Measured: Ongoing
Secondary outcomes (3)
Assess ability to participate in other studies
To assess the patient's ability to safely tolerate specific aspects of other diagnostic or therapeutic research protocols.
Measured: ongoing
Determine eligibility for other studies
To determine a patient's eligibility for other studies.
Measured: ongoing
Establish baseline of pattern/pace of disease process before participating in therapeutic trials
To establish a baseline assessment of the pace and extent of the disease before entering a therapeutic clinical trial.
Measured: ongoing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study start15 Jan 1990
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for XLAStudies 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Warren Strober, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001244
- Sponsor's protocol ID
- 890158
- Other IDs
- 89-I-0158
- Status last verified
- 14 Apr 2026
- First submitted
- 3 Nov 1999
- Last updated
- 29 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Jaffe JS, Eisenstein E, Sneller MC, Strober W. T-cell abnormalities in common variable immunodeficiency. Pediatr Res. 1993 Jan;33(1 Suppl):S24-7; discussion S27-8. doi: 10.1203/00006450-199305001-00128.
PubMed 7679486Mannon PJ, Fuss IJ, Dill S, Friend J, Groden C, Hornung R, Yang Z, Yi C, Quezado M, Brown M, Strober W. Excess IL-12 but not IL-23 accompanies the inflammatory bowel disease associated with common variable immunodeficiency. Gastroenterology. 2006 Sep;131(3):748-56. doi: 10.1053/j.gastro.2006.06.022.
PubMed 16952544Cunningham-Rundles C. Autoimmune manifestations in common variable immunodeficiency. J Clin Immunol. 2008 May;28 Suppl 1(Suppl 1):S42-5. doi: 10.1007/s10875-008-9182-7. Epub 2008 Mar 6.
PubMed 18322785
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Studies of Immune Regulation in Patients With Common Variable Immunodeficiency and Related Inborn Errors of Immunity (IEI)
- ClinicalTrials.gov ID
- NCT00001244
- Acronym / sponsor ID
- 890158
- Conditions
- XLA, CVID, Yao Syndrome, Blau Syndrome
- Keywords
- Blau Syndrome, XLA, Humoral Immunodeficiency, CVID enteropathy, CVID, Agammaglobulinemia, Inborn Errors of Immunity, Yao Syndrome
- 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
- 15 Jan 1990 (actual)
- First posted
- 4 Nov 1999 (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.
This study aims to understand the causes and progression of Common Variable Immunodeficiency (CVID) and related inborn errors of immunity (IEI). These are conditions where the immune system does not function properly, leading to frequent infections and other complications such as gastrointestinal inflammation, lung and liver disease, autoimmune conditions, and an increased risk of certain cancers. By studying patients with CVI and related immune disorders, we hope to develop better ways to diagnose, treat, and prevent complications associated with these conditions.
Patients diagnosed with CVID or related immune disorders must be referred by their physician and medical records reviewed by the study team to confirm eligibility to participate in this study. Once enrolled, participants will undergo various tests, including blood draws, physical exams, and imaging studies like CT scans to track changes over time. We may collect samples such as blood, urine, stool, or saliva for research purposes. If a surgical procedure or biopsy is performed because it is medically necessary, we may collect an additional sample for research testing. Family members of patients may be asked to provide blood samples for comparison. Some tests may be done remotely if participants or family members cannot travel to the study site.
Who Can Participate
- Patients diagnosed with CVI or related IEI, such as X-linked agammaglobulinemia, Blau Syndrome or Yao Syndrome.
- Participants must be at least 2 years old.
- Family members of patients may include parents, siblings, grandparents, children, aunts, uncles, and cousins.
- Pregnant women already enrolled in the study will continue to participate, but new pregnant participants will not be enrolled.
Potential Risks and Benefits
- Risks: Blood draws may cause discomfort, bruising, or infection. Apheresis may cause dizziness, nausea, or muscle cramps; this procedure is to collect specific cells in the blood and is infrequently done on this protocol. Extra biopsies during clinically indicated procedures may increase the risk of complications; they will only be collected after the medically necessary biopsies are taken and if it is safe to collect any extra biopsies.
- Benefits: Participants may not receive direct medical benefits, but the study will contribute to a better understanding of CVID and related conditions, potentially leading to improved treatments.
Detailed description
The purpose of this protocol is to carry out laboratory studies concerning the immunopathogenesis of Common Variable Immunodeficiency (CVI) and related inborn errors of immunity (IEI). Additionally, we aim to document and track the progression of known complications of these immune abnormalities. Complications associated with CVI include recurrent respiratory, granulomas, pulmonary insufficiency, gastrointestinal bacterial infections, enteropathy, nodular regenerative hyperplasia, lymphoid malignancy, and various autoimmune manifestations.
Patients with CVI and related IEI will be enrolled into this natural history study. Protocol procedures will include baseline measurements of and changes in lab studies. First- or second-degree genetically related family members (limited to mother, father, siblings, grandparents, children, aunts, uncles, and first cousins of an affected patient) may also be screened for clinical, in vitro, and genetic correlates of immune abnormalities. Changes in the patients' clinical state will be measured to determine the precursors of disease complications. This may lead to developments in improving preventive measures and novel treatment options for this population.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| General Population | – | –Physician referral required |
Who may qualify
- Ages
- 2 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- General population - Physician referral required
Key inclusion criteria (9 listed)
- Must have a verifiable diagnosis of common variable immune deficiency as defined by a decrease both in IgG and at least one other Ig isotype to below two standard deviations of normal control levels OR B-cell immunodeficiencies related to CVI (defined as selective IgA deficiency, selective IgG isotype deficiency, agammaglobulinemia, and hypogammaglobulinemia associated with Epstein-Barr virus infection), or hypogammaglobulinemia associated with other related inborn errors of immunity. This includes patients with a defined diagnosis of Blau or Yao Syndrome.
- Must be 2 years old or greater.
- Patients with repeated infections and suspected of having an inborn error of immunity.
- Patients must be referred by their primary medical care provider.
- On investigator s discretion, unaffected family members (mother, father, siblings, children, grandparents, aunts, uncles, and first cousins) may be asked for the provision of blood or buccal specimens for research purposes.
Key exclusion criteria (4 listed)
- Presence of other medical illnesses that would preclude individuals from undergoing routine diagnostic testing or testing for immunologic features of immunodeficiency.
- Presence of a condition or treatment, such as HIV, cytotoxic chemotherapy or malignancy, that in the investigator s opinion could interfere with evaluation of the condition under study.
- Pregnancy at the time of enrollment.
- Inability of an adult participant to provide informed consent for themselves (decisionally impaired adult).
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
Establish pattern/pace of disease process
Time frame: At 1 year and ongoing
To establish the pattern and pace of change of disease (frequency, distribution, type and extent of infections, inflammatory lesions and abnormalities of immune function).
Evaluation of organ dysfunction/damage resulting from immune abnormality
Time frame: Ongoing
To establish the extent of organ involvement (infection and/or inflammation) and organ damage or dysfunction resulting from the abnormality of immune function.
Characterization of immune abnormalities
Time frame: Ongoing
To characterize the physiologic, biochemical or genetic basis of theabnormality of immunity.
3 secondary outcomes
Assess ability to participate in other studies
Time frame: ongoing
Determine eligibility for other studies
Time frame: ongoing
Establish baseline of pattern/pace of disease process before participating in therapeutic trials
Time frame: ongoing
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 29 Oct 2026.
- Background: PubMed 7679486Jaffe JS, Eisenstein E, Sneller MC, Strober W. T-cell abnormalities in common variable immunodeficiency. Pediatr Res. 1993 Jan;33(1 Suppl):S24-7; discussion S27-8. doi: 10.1203/00006450-199305001-00128.
- Background: PubMed 16952544Mannon PJ, Fuss IJ, Dill S, Friend J, Groden C, Hornung R, Yang Z, Yi C, Quezado M, Brown M, Strober W. Excess IL-12 but not IL-23 accompanies the inflammatory bowel disease associated with common variable immunodeficiency. Gastroenterology. 2006 Sep;131(3):748-56. doi: 10.1053/j.gastro.2006.06.022.
- Background: PubMed 18322785Cunningham-Rundles C. Autoimmune manifestations in common variable immunodeficiency. J Clin Immunol. 2008 May;28 Suppl 1(Suppl 1):S42-5. doi: 10.1007/s10875-008-9182-7. Epub 2008 Mar 6.
- 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.
Warren Strober, 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 XLA and CVID, 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 9 inclusion and 4 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 29 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 Kimberly L Montgomery-Recht, R.N. ((240) 422-7966, kim.montgomery-recht@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Establish pattern/pace of disease process (time frame: At 1 year and ongoing). The study lists 3 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 NCT00001244, which also lists 3 linked publications.
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 29 Oct 2026.