Immune System and Gut Abnormalities in Patients With Common Variable Immunodeficiency With and Without Gastrointestinal Symptoms
|First Received Date ICMJE||April 18, 2001|
|Last Updated Date||December 19, 2012|
|Start Date ICMJE||April 2001|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00015431 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Immune System and Gut Abnormalities in Patients With Common Variable Immunodeficiency With and Without Gastrointestinal Symptoms|
|Official Title ICMJE||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.
Participants will be admitted to the NIH Clinical Center for several days to undergo the following procedures:
Identification of GI abnormalities associated with changes in immune response in CVID patients will help in developing and testing new treatments for this disease.
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 Type ICMJE||Observational|
|Study Design ICMJE||Not Provided|
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Condition ICMJE||Common Variable Immunodeficiency|
|Intervention ICMJE||Not Provided|
|Study Group/Cohort (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||40|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
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.
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.
|Ages||10 Years and older|
|Accepts Healthy Volunteers||No|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT00015431|
|Other Study ID Numbers ICMJE||010153, 01-I-0153|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Institute of Allergy and Infectious Diseases (NIAID)|
|Collaborators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||September 2012|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP