INCLUSION CRITERIA:
Group One:
Must have a confirmed CGD diagnosis by the absence of respiratory oxidative burst by a dihydrorhodamine release assay (DHR) or mutations of one of the four components of phagocytic oxidative system
Must have IBD documented by medical history or documented IBD endoscopically.
Must be asymptomatic
Must be 3 years old or older and weigh greater than or equal to 15 kg.
Must have negative results on stool examination for culture of enteric pathogens (Salmonella, Shigella, Yersinia, Campylobacter, Vibrio, E. coli O157/H7), Clostridium difficile toxin assay, enteric parasites and their ova (including Cryptosporidia, Cyclospora, Microsporidia and Giardia (by stool enzyme immunoassay [EIA]).
Must not be pregnant or breastfeeding
If of child-bearing potential, must agree to consistently use contraception throughout study participation. Acceptable forms of contraception are:
-Condoms, male or female, with or without a spermicide
-Diaphragm or cervical cap with spermicide
-Intrauterine device
-Contraceptive pills or patch, Norplant, Depo-Provera or other FDA-approved contraceptive method
-Male partner has previously undergone a vasectomy for which there is documentation of aspermatogenic sterility.
Must have a recent chest CT (within 3 months) to confirm absence of tuberculosis (TB) infection
Must have a home physician
Must be willing to submit samples for storage.
Group Two:
Must have a confirmed CGD diagnosis by the absence of respiratory oxidative burst by DHR or mutations of one of the four components of phagocytic oxidative system.
Must have IBD documented by medical history or documented IBD endoscopically.
Must have symptomatic IBD.
Must be 3 years old or older and weigh greater than or equal to 15 kg.
Must have negative results on stool examination for culture of enteric pathogens (Salmonella, Shigella, Yersinia, Campylobacter, Vibrio, E. coli O157/H7), Clostridium difficile toxin assay, enteric parasites and their ova (including Cryptosporidia, Cyclospora, Microsporidia and Giardia (by stool EIA).
Must not be pregnant or breastfeeding
If of child-bearing potential, must agree to consistently use contraception throughout study participation. Acceptable forms of contraception are:
-Condoms, male or female, with or without a spermicide
-Diaphragm or cervical cap with spermicide
-Intrauterine device
-Contraceptive pills or patch, Norplant, Depo-Provera or other FDA-approved contraceptive method
-Male partner has previously undergone a vasectomy for which there is documentation of aspermatogenic sterility.
Must have a recent chest CT (within 3 months) to confirm absence of TB infection.
Must have a home physician
Must be willing to submit samples for storage
Group Three:
Must have a confirmed CGD diagnosis by the absence of respiratory oxidative burst by a dihydrorhodamine release assay (DHR) or mutations of one of the four components of phagocytic oxidative system.
Must be greater than or equal to 18 years old and greater than or equal to 15 kg.
Must not be pregnant.
Must be willing to submit samples for storage.
EXCLUSION CRITERIA:
Group One:
Patients with positive test for HIV or signs and symptoms consistent with HIV infection
CGD patients with symptomatic IBD
Patient less than 3 years old
Weight less than 15 kg
Non-CGD patients
Pregnancy or breastfeeding
Positive TB diagnosis per CT scan
CGD patients without a history of IBD
Patients who are in the at-risk group for treatment with infliximab such as history of tuberculosis, congestive cardiac failure or unstable angina, thrombocytopenia (platelet less than 100, 000), uncontrolled hypertension
Any of the following abnormalities on an electrocardiogram: QTC greater than 0.48sec, Mobitz type II second or third degree atrioventricular block, left bundle branch block or right bundle branch block with any fascicular block, changes consistent with acute ischemia.
Severe persistent asthma defined as the presence of one of the features listed below:
a. Continuous respiratory symptoms
b. Frequent exacerbations
c. Frequent night-time asthma symptoms
d. Physical activities limited by asthma symptoms
e. Peak expiratory flow rate (PEF) or forced expiratory volume 1 (FEV1) less than 60% predicted, variability greater than 30%
Daily medications required to maintain control such as high-dose corticosteroids, long-acting bronchodilators or oral corticosteroids
Acute systemic or intestinal infection requiring antibiotics
Evidence of Hepatitis B or C infection
Signs and symptoms of hepatotoxicity
Pregnant or breastfeeding
History of cancer within the last 10 years
History of myocardial infarction within the last 12 months
Any condition that, in the investigator's opinion, places the patient at undue risk by participating in the study
History of anaphylactic reaction or hypersensitivity to Infliximab or proteins derived from E. coli.
The presence of certain types of acquired abnormalities of immunity such as HIV, cytotoxic chemotherapy for malignancy could be grounds for possible exclusion if, in the opinion of the investigator, the presence of such disease process interferes with evaluation of a co-existing abnormality of immunity that is a subject of study under this protocol.
Co-existing Th2-type inflammatory disease
Current active bowel obstruction, intestinal perforation, or significant GI hemorrhage.
Positive TB diagnosis per CT scan
Live vaccine within 4 weeks prior to therapy or potential need for a live vaccine during the study.
Unwillingness to undergo testing or procedures associated with this protocol.
Group Two:
Patients with positive test for HIV or signs and symptoms consistent with HIV infection
Non-CGD patients
Patient less than 3 years old
Weight less than 15 kg
CGD patients with no symptoms of IBD
Patients who are in the at-risk group for treatment with infliximab such as history of tuberculosis, congestive cardiac failure or unstable angina, thrombocytopenia (platelet less than 100, 000), uncontrolled hypertension
Any of the following abnormalities on an electrocardiogram: QTC greater than 0.48sec, Mobitz type II second or third degree atrioventricular block, left bundle branch block or right bundle branch block with any fascicular block, changes consistent with acute ischemia.
Severe persistent asthma defined as the presence of one of the features listed below:
f. Continuous respiratory symptoms
g. Frequent exacerbations
h. Frequent night-time asthma symptoms
i. Physical activities limited by asthma symptoms
j. Peak expiratory flow rate (PEF) or forced expiratory volume 1 (FEV1) less than 60% predicted, variability greater than 30%
k. Daily medications required to maintain control such as high-dose corticosteroids, long-acting bronchodilators or oral corticosteroids
Acute systemic or intestinal infection requiring antibiotics
Evidence of Hepatitis B or C infection
Signs and symptoms of hepatotoxicity
Pregnant or breastfeeding
History of cancer within the last 10 years
History of myocardial infarction within the last 12 months
Any condition that, in the investigator's opinion, places the patient at undue risk by participating in the study
The presence of certain types of acquired abnormalities of immunity such as HIV, cytotoxic chemotherapy for malignancy could be grounds for possible exclusion if, in the opinion of the investigator, the presence of such disease process interferes with evaluation of a co-existing abnormality of immunity that is a subject of study under this protocol.
Co-existing Th2-type inflammatory disease
Current active bowel obstruction, intestinal perforation, or significant GI hemorrhage.
Positive TB diagnosis per CT scan
Live vaccine within 4 weeks prior to therapy or potential need for a live vaccine during the study.
Inability or unwillingness to undergo testing or procedures associated with this protocol.
Group Three:
Patients with positive test for HIV or signs and symptoms consistent with HIV infection
Patients less than 18 years old, or weighs less than 15 kg
Pregnancy
Acute systemic or intestinal infection requiring antibiotics
Any condition that, in the investigator's opinion, places the patient at undue risk by participating in the study
The presence of certain types of acquired abnormalities of immunity such as HIV, cytotoxic chemotherapy for malignancy could be grounds for possible exclusion if, in the opinion of the investigator, the presence of such disease process interferes with evaluation of a co-existing abnormality of immunity that is a subject of study under this protocol.
Unwillingness to undergo testing of procedures associated with this protocol.
National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 01/30/2009