Common Variable ImmunodeficiencyNCT00015431
Immune System and Gut Abnormalities in Patients With Common Variable Immunodeficiency With and Without Gastrointestinal Symptoms
An observational study of Common Variable Immunodeficiency, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
This study will determine whether people with common variable immunodeficiency (CVID) with and without gastrointestinal (GI) symptoms have gut abnormalities (inflammation or loss of function) and changes in immune system cells and chemicals in the blood and gut. Read more about this study
- Who is it for?
- Ages 10 years and older
- Conditions the study is for
- Common Variable Immunodeficiency
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Apr 2001to 10 Jul 2013
- Phase
- Observational
- Are there results?
- None posted in the registry
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 10 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Must have a verifiable diagnosis of common variable immune deficiency specifically a decrease both in IgG and at least one other Ig isotype to below two standard deviations of normal control levels.
- Must be age 10 years old or older for patients with gastrointestinal symptoms or age 18 years or older in the absence of gastrointestinal symptoms.
- Must be free of active sinopulmonary or other infection at time of enrollment.
- Must have negative results on stool examination for culture of enteric pathogens (Salmonella, Shigella, Yersinia, Campylobacter, Vibrio, E. Coli O157/H7), Clostridia difficile toxin assay, enteric parasites and their ova (including Cryptosporidia, Cyclospora, Microsporidia and Giardia (by stool EIA)).
- Adults who are unable to provide initial or on-going consent may participate in this study.
Who cannot join
- Absence of other antibody deficiency states including X-linked agammaglobulinemia, hyper IgM syndrome, selective deficiency of IgG subclass, and Ig heavy chain gene deletions.
- Use of immunomodulating drugs within the following times prior to enrollment: daily corticosteroids (4 weeks), azathioprine/6-MP, cyclosporine, methotrexate, or FK506 (3 months). The use of short-term or single dose corticosteroids as a pretreatment regimen for IVIG is acceptable.
- Positive test for anti-HIV.
- Significant systemic or major disease including congestive heart failure, coronary artery disease, cerebrovascular disease and pre-existing or recent onset CNS demyelinating disorder, pulmonary disease, renal failure, organ transplantation, decompensated liver disease, serious psychiatric disease, or malignancy that in the opinion of the investigator would preclude successful endoscopic evaluation.
- Pregnancy, to avoid endoscopies without a strictly therapeutic intent in this relatively high risk population.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: The Immune Basis for the Gastrointestinal Complications of Common Variable Immunodeficiency
This study will determine whether people with common variable immunodeficiency (CVID) with and without gastrointestinal (GI) symptoms have gut abnormalities (inflammation or loss of function) and changes in immune system cells and chemicals in the blood and gut. People with CVID have decreased levels of serum immunoglobulin IgG and IgA. Patients have sinus, lung and other infections, and many also have stomach and intestinal problems, such as chronic diarrhea, inability to absorb nutrition from food, and intestinal infections caused by bacteria.
CVID patients with gastrointestinal symptoms 10 years of age and older may be eligible for this study; CVID patients without gastrointestinal symptoms 18 years of age and older will be enrolled as control subjects. Candidates will be screened with a review of their medical records, a medical history and physical examination, HIV blood test, stool sample, and hydrogen breath test. The breath test measures the amount of hydrogen in the breath after drinking sugar water, showing the digestive effects of bacteria in the upper intestine.
Read more
Participants will be admitted to the NIH Clinical Center for several days to undergo the following procedures:
- Medical history and physical examination
- Blood tests
- Urine and stool samples
- 48-hour stool fat collection measures the amount of undigested fat in the stool to determine the ability of the gut to digest and absorb fat in the diet
- D-Xylose absorption test measures the ability of a sugar compound to travel across the lining of the intestine to determine the ability of the gut to absorb nutrients
- Upper endoscopy a thin flexible lighted tube is advanced through the mouth to evaluate the esophagus, stomach and beginning of the small intestine
- Lower endoscopy a thin lighted tube is advanced through the rectum to evaluate the colon
Identification of GI abnormalities associated with changes in immune response in CVID patients will help in developing and testing new treatments for this disease.
Read the detailed description
Common variable immunodeficiency (CVID) is a clinically heterogeneous disorder characterized by decreased serum immunoglobulin IgG and IgA levels. In addition to chronic or recurrent sinopulmonary infections, many patients develop gastrointestinal manifestations that can be disabling or fatal. Data suggest that these gut abnormalities have a primary immune basis, implicating T cells primarily, and are not related to the infectious complications of CVID. Currently there is no standard therapy for the associated gastrointestinal disease outside of empiric nutritional intervention for weight loss and non-specific anti-diarrheal agents. In addition there is no data about the prevalence of gastrointestinal abnormalities in CVID patients who have no overt gastrointestinal symptoms.
The objectives of this study are to characterize the gastrointestinal abnormalities that occur in CVID patients and correlate this with the immunophenotype and cytokine secretion of peripheral blood and lamina propria lymphocytes and monocytes. CVID patients with gastrointestinal symptoms of malabsorption/maldigestion and chronic diarrhea will be targeted for study. We will also include a group of patients without gastrointestinal symptoms to provide an estimate of background prevalence and severity of gut abnormalities. Subjects will undergo a standard immunologic workup including peripheral blood lymphocyte marker phenotyping and cytokine responses as well as tests of gastrointestinal absorption, examination of gut histology by endoscopic biopsy, and measurement of gut mucosal cytokine expression. Analysis variables will include clinical (weight, stool frequency, results of gut absorption tests), laboratory (lymphocyte and cytokine assays), and gut abnormalities (histology scores and specific lesions).
- Conditions
- Common Variable Immunodeficiency
- Keywords
- Malabsorption, Endoscopy, Cytokine, Immunophenotype, Lymphocyte, Common Variable Immunodeficiency, Gastrointestinal
- Medical subject headings
- Common Variable Immunodeficiency, Malabsorption Syndromes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2001 (estimated)
- Study start16 Apr 2001
- Study completion10 Jul 2013
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 Common Variable ImmunodeficiencyStudies 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
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Investigators
- Ivan J Fuss, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00015431
- Sponsor's protocol ID
- 010153
- Other IDs
- 01-I-0153
- Status last verified
- 10 Jul 2013
- First submitted
- 18 Apr 2001
- Last updated
- 29 Mar 2019
- Results posted
- No
Publications
Schaffer FM, Palermos J, Zhu ZB, Barger BO, Cooper MD, Volanakis JE. Individuals with IgA deficiency and common variable immunodeficiency share polymorphisms of major histocompatibility complex class III genes. Proc Natl Acad Sci U S A. 1989 Oct;86(20):8015-9. doi: 10.1073/pnas.86.20.8015.
PubMed 2573059Wagner DK, Wright JJ, Ansher AF, Gill VJ. Dysgonic fermenter 3-associated gastrointestinal disease in a patient with common variable hypogammaglobulinemia. Am J Med. 1988 Feb;84(2):315-8. doi: 10.1016/0002-9343(88)90432-9.
PubMed 3407657Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol. 1999 Jul;92(1):34-48. doi: 10.1006/clim.1999.4725.
PubMed 10413651
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Immune Basis for the Gastrointestinal Complications of Common Variable Immunodeficiency
- ClinicalTrials.gov ID
- NCT00015431
- Acronym / sponsor ID
- 010153
- Conditions
- Common Variable Immunodeficiency
- Keywords
- Malabsorption, Endoscopy, Cytokine, Immunophenotype, Lymphocyte, Common Variable Immunodeficiency, Gastrointestinal
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 16 Apr 2001
- Study completion
- 10 Jul 2013
- First posted
- 19 Apr 2001 (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 will determine whether people with common variable immunodeficiency (CVID) with and without gastrointestinal (GI) symptoms have gut abnormalities (inflammation or loss of function) and changes in immune system cells and chemicals in the blood and gut. People with CVID have decreased levels of serum immunoglobulin IgG and IgA. Patients have sinus, lung and other infections, and many also have stomach and intestinal problems, such as chronic diarrhea, inability to absorb nutrition from food, and intestinal infections caused by bacteria.
CVID patients with gastrointestinal symptoms 10 years of age and older may be eligible for this study; CVID patients without gastrointestinal symptoms 18 years of age and older will be enrolled as control subjects. Candidates will be screened with a review of their medical records, a medical history and physical examination, HIV blood test, stool sample, and hydrogen breath test. The breath test measures the amount of hydrogen in the breath after drinking sugar water, showing the digestive effects of bacteria in the upper intestine.
Participants will be admitted to the NIH Clinical Center for several days to undergo the following procedures:
- Medical history and physical examination
- Blood tests
- Urine and stool samples
- 48-hour stool fat collection measures the amount of undigested fat in the stool to determine the ability of the gut to digest and absorb fat in the diet
- D-Xylose absorption test measures the ability of a sugar compound to travel across the lining of the intestine to determine the ability of the gut to absorb nutrients
- Upper endoscopy a thin flexible lighted tube is advanced through the mouth to evaluate the esophagus, stomach and beginning of the small intestine
- Lower endoscopy a thin lighted tube is advanced through the rectum to evaluate the colon
Identification of GI abnormalities associated with changes in immune response in CVID patients will help in developing and testing new treatments for this disease.
Detailed description
Common variable immunodeficiency (CVID) is a clinically heterogeneous disorder characterized by decreased serum immunoglobulin IgG and IgA levels. In addition to chronic or recurrent sinopulmonary infections, many patients develop gastrointestinal manifestations that can be disabling or fatal. Data suggest that these gut abnormalities have a primary immune basis, implicating T cells primarily, and are not related to the infectious complications of CVID. Currently there is no standard therapy for the associated gastrointestinal disease outside of empiric nutritional intervention for weight loss and non-specific anti-diarrheal agents. In addition there is no data about the prevalence of gastrointestinal abnormalities in CVID patients who have no overt gastrointestinal symptoms.
The objectives of this study are to characterize the gastrointestinal abnormalities that occur in CVID patients and correlate this with the immunophenotype and cytokine secretion of peripheral blood and lamina propria lymphocytes and monocytes. CVID patients with gastrointestinal symptoms of malabsorption/maldigestion and chronic diarrhea will be targeted for study. We will also include a group of patients without gastrointestinal symptoms to provide an estimate of background prevalence and severity of gut abnormalities. Subjects will undergo a standard immunologic workup including peripheral blood lymphocyte marker phenotyping and cytokine responses as well as tests of gastrointestinal absorption, examination of gut histology by endoscopic biopsy, and measurement of gut mucosal cytokine expression. Analysis variables will include clinical (weight, stool frequency, results of gut absorption tests), laboratory (lymphocyte and cytokine assays), and gut abnormalities (histology scores and specific lesions).
Study design
Who may qualify
- Ages
- 10 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Must have a verifiable diagnosis of common variable immune deficiency specifically a decrease both in IgG and at least one other Ig isotype to below two standard deviations of normal control levels.
- Must be age 10 years old or older for patients with gastrointestinal symptoms or age 18 years or older in the absence of gastrointestinal symptoms.
- Must be free of active sinopulmonary or other infection at time of enrollment.
- Must have negative results on stool examination for culture of enteric pathogens (Salmonella, Shigella, Yersinia, Campylobacter, Vibrio, E. Coli O157/H7), Clostridia difficile toxin assay, enteric parasites and their ova (including Cryptosporidia, Cyclospora, Microsporidia and Giardia (by stool EIA)).
- Adults who are unable to provide initial or on-going consent may participate in this study.
Key exclusion criteria (5 listed)
- Absence of other antibody deficiency states including X-linked agammaglobulinemia, hyper IgM syndrome, selective deficiency of IgG subclass, and Ig heavy chain gene deletions.
- Use of immunomodulating drugs within the following times prior to enrollment: daily corticosteroids (4 weeks), azathioprine/6-MP, cyclosporine, methotrexate, or FK506 (3 months). The use of short-term or single dose corticosteroids as a pretreatment regimen for IVIG is acceptable.
- Positive test for anti-HIV.
- Significant systemic or major disease including congestive heart failure, coronary artery disease, cerebrovascular disease and pre-existing or recent onset CNS demyelinating disorder, pulmonary disease, renal failure, organ transplantation, decompensated liver disease, serious psychiatric disease, or malignancy that in the opinion of the investigator would preclude successful endoscopic evaluation.
- Pregnancy, to avoid endoscopies without a strictly therapeutic intent in this relatively high risk population.
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
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2019.
- Background: PubMed 2573059Schaffer FM, Palermos J, Zhu ZB, Barger BO, Cooper MD, Volanakis JE. Individuals with IgA deficiency and common variable immunodeficiency share polymorphisms of major histocompatibility complex class III genes. Proc Natl Acad Sci U S A. 1989 Oct;86(20):8015-9. doi: 10.1073/pnas.86.20.8015.
- Background: PubMed 3407657Wagner DK, Wright JJ, Ansher AF, Gill VJ. Dysgonic fermenter 3-associated gastrointestinal disease in a patient with common variable hypogammaglobulinemia. Am J Med. 1988 Feb;84(2):315-8. doi: 10.1016/0002-9343(88)90432-9.
- Background: PubMed 10413651Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol. 1999 Jul;92(1):34-48. doi: 10.1006/clim.1999.4725.
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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. This study is not recruiting at the moment.
Ivan J Fuss, 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 Common Variable Immunodeficiency, 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 5 inclusion and 5 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: finished, as of the sponsor's last update on 29 Mar 2019. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00015431, 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 Mar 2019; AzTrials last refreshed its copy on 30 Oct 2026.