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.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

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Trial summary

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

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.

Kimberly L Montgomery-Recht, R.N. contact

(240) 422-7966

kim.montgomery-recht@nih.gov

United States1 site, 1 recruiting

National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
Ivan Fuss, M.D., 301-761-7091, ifuss@niaid.nih.gov
Recruiting

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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.

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 groups in NCT00001244
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.

15 Jan 1990?

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)

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: 8 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 7679486
Mannon 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 16952544
Cunningham-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