Chronic Granulomatous Disease Clinical Trial
Official title:
Tumor Necrosis Factor Alpha Inhibitor (Lnfliximab, Adalimumab) Treatment for Crohn'S-like Inflammatory Bowel Disease in Chronic Granulomatous Disease: A Phase I/II Study Assessing Clinical and Immune Responses to Treatment and Genetic Influences
This study will determine if the drug infliximab is safe for treating inflammatory bowel
disease (IBD) in patients with chronic granulomatous disease (CGD). IBD is an inflammation
or irritation of the gut that leads to symptoms such as diarrhea, bloating and stomach
cramps. CGD is an inherited disease affecting white blood cells called neutrophils in which
patients are susceptible to repeated bacterial and fungal infections. They also have a
higher incidence of some autoimmune diseases, such as IBD. Infliximab is approved to treat
Crohn's disease, an IBD similar to that seen in patients with CGD.
Patients 10 years of age and older with CGD and IBD may be eligible for this study.
Candidates are screened with a medical history, physical examination, blood and urine tests,
electrocardiogram (EKG), tuberculosis skin test (PPD skin testing), and stool test for the
presence of infections. Additional tests may be done, including colonoscopy (procedure using
a flexible tube through the rectum to examine the lining of the gut) and imaging studies
such as an x-ray, chest CT scan (test using a special x-ray machine), MRI (test using a
magnetic field and radio waves), and barium studies (study using a drinkable solution of
barium to help enhance the x-ray pictures of the gut).
Participants are divided into patients with IBD symptoms (Group 1) and patients without IBD
symptoms (Group 2) for the following procedures:
Group 1
Patients are evaluated every 6 months with a medical history and physical examination for
signs and symptoms of IBD. Patients who are taking moderate to high doses of steroid
medications have their medication slowly lowered (tapered) and are evaluated every 3 months
for a total of 2 years. Patients in this group who start to develop IBD symptoms are moved
to Group 2 for treatment with infliximab (see below).
Group 2
Patients in Group 2 receive infliximab infusions at 2-week intervals for three doses. The
drug is given over a 2-hour period through a catheter placed in a vein. Patients are
evaluated with a medical history, physical exam, and blood tests the day of each dose. One
week after the last dose, they have another evaluation, including a colonoscopy. Patients
who respond well to infliximab may continue to receive the drug every 2 months for a total
of 1 year, with evaluations at every dosing visit. At the end of the first year of receiving
infliximab, all patients have follow-up evaluations every 6 months for a total of 2 years.
Group 3
Subjects who volunteer to undergo colonoscopy and research biopsies that serve as controls
for evaluation of the patient gut samples.
Status | Terminated |
Enrollment | 40 |
Est. completion date | June 2012 |
Est. primary completion date | June 2012 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | Both |
Age group | 10 Years and older |
Eligibility |
- INCLUSION CRITERIA: Group One - Must have a confirmed CGD diagnosis - Must have IBD documented by medical history or documented IBD endoscopically. - Must not be pregnant or breastfeeding - Must have a home physician - Must be willing to submit samples for storage. Group Two: - Must have a confirmed CGD diagnosis - Must have IBD documented by medical history or documented IBD endoscopically. - Must be symptomatic - Must have negative results on stool examination for culture of enteric pathogens, such as Salmonella, Shigella, Yersinia, Campylobacter, E. coli O157/H7, Clostridium difficile toxin assay, enteric parasites and their ova such as Cryptosporidia, Cyclospora, Microsporidia and Giardia (by stool enzyme immunoassay [EIA]) prior to the start of receiving TNF? inhibitors. - Must not be pregnant or breastfeeding - If of childbearing potential, one must agree to consistently use contraception, while on the study medication. - 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 Three: - Must be willing to undergo upper and lower endoscopy and mucosal biopsies for research purpose - Must be greater than or equal to 18 years old and weigh greater than or equal to 15 kg. - Must not be pregnant - Must be willing to submit samples for storage. EXCLUSION CRITERIA: Group One: - Any condition that, in the investigator's opinion, places the patient at undue risk by participating in the study. Group Two: - Any condition that, in the investigator's opinion, places the patient at undue risk by participating in the study - Positive TB diagnosis - Patients who are in the at-risk group for treatment such as history of tuberculosis, congestive cardiac failure or myocardial infarction within the last 12 months unstable angina, thrombocytopenia (platelet < 100, 000), uncontrolled hypertension - Acute systemic or intestinal infection(s) - Evidence of Hepatitis B or C infection - Signs and symptoms of hepatotoxicity - Pregnant or breastfeeding - History of cancer within the last 10 years - 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. - 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 Three: - 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 or procedures associated with this protocol. |
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
United States | National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland |
Lead Sponsor | Collaborator |
---|---|
National Institute of Allergy and Infectious Diseases (NIAID) |
United States,
Buckner CM, Moir S, Kardava L, Ho J, Santich BH, Kim LJ, Funk EK, Nelson AK, Winckler B, Chairez CL, Theobald-Whiting NL, Anaya-O'Brien S, Alimchandani M, Quezado MM, Yao MD, Kovacs JA, Chun TW, Fauci AS, Malech HL, De Ravin SS. CXCR4/IgG-expressing plasma cells are associated with human gastrointestinal tissue inflammation. J Allergy Clin Immunol. 2014 Jun;133(6):1676-85.e5. doi: 10.1016/j.jaci.2013.10.050. Epub 2013 Dec 25. — View Citation
Segal BH, Leto TL, Gallin JI, Malech HL, Holland SM. Genetic, biochemical, and clinical features of chronic granulomatous disease. Medicine (Baltimore). 2000 May;79(3):170-200. Review. — View Citation
Vignais PV. The superoxide-generating NADPH oxidase: structural aspects and activation mechanism. Cell Mol Life Sci. 2002 Sep;59(9):1428-59. Review. — View Citation
Winkelstein JA, Marino MC, Johnston RB Jr, Boyle J, Curnutte J, Gallin JI, Malech HL, Holland SM, Ochs H, Quie P, Buckley RH, Foster CB, Chanock SJ, Dickler H. Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine (Baltimore). 2000 May;79(3):155-69. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Gut Immune Cell Types and Their Cytokine Profile | Gut Immune cell types and their cytokine profile | 1 year | Yes |
Primary | Safety of Study Drug | Number of Infections from Baseline to 1 year | Baseline to 1 year | Yes |
Primary | Efficacy of Treatment With Study Drug | Measured participant Crohn's disease Activity Index (CDAI) values. The CDAI is a tool comprised of clinical and laboratory factors such as stool frequency, consistency, abdominal pain, general well being, weight and blood profile as an objective measure of disease activity. A higher score corresponds to greater severity of inflammatory bowel disease; severe disease conventionally defined as >450, a remission as <150, and a response to treatment as a fall of CDAI of >70 points. Infections and IBD are not expected in healthy control subjects. The greater the score, the more severe the disease, and a score of less than 5 represents clinical remission. | Baseline, 1 year | No |
Status | Clinical Trial | Phase | |
---|---|---|---|
Withdrawn |
NCT03278912 -
Natural History of Intestinal Inflammation in People With Primary Immune Dysregulations
|
||
Recruiting |
NCT01652092 -
Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies
|
N/A | |
Completed |
NCT04136028 -
IL-1 Receptor Inhibitor for Granulomatous Complications in Patients With Chronic Granulomatous Disease
|
Early Phase 1 | |
Recruiting |
NCT05687474 -
Baby Detect : Genomic Newborn Screening
|
||
Terminated |
NCT03080480 -
Pioglitazone Therapy for Chronic Granulomatous Disease
|
Phase 1/Phase 2 | |
Terminated |
NCT00394316 -
Gene Therapy for Chronic Granulomatous Disease
|
Early Phase 1 | |
Recruiting |
NCT03910452 -
Haploidentical Transplant for People With Chronic Granulomatous Disease (CGD) Using Alemtuzumab, Busulfan and TBI With Post-Transplant Cyclophosphamide
|
Early Phase 1 | |
Terminated |
NCT02282904 -
Haploidentical Transplant for People With Chronic Granulomatous Disease Using Post Transplant Cyclophosphamide
|
Phase 1/Phase 2 | |
Terminated |
NCT02926963 -
Generation of Powerful Biological Tools for Understanding the Pathophysiology of Chronic Granulomatous Disease.
|
N/A | |
Completed |
NCT00006417 -
Modified Stem Cell Transplantation Procedure for Treating Chronic Granulomatous Disease
|
Phase 2 | |
Completed |
NCT00368446 -
Genetic Disorders of Mucociliary Clearance in Nontuberculous Mycobacterial Lung Disease
|
||
Enrolling by invitation |
NCT03655223 -
Early Check: Expanded Screening in Newborns
|
||
Recruiting |
NCT06162936 -
Neutrophil Oxidative Burst in Early and Late Onset Pediatric Inflammatory Bowel Disease
|
||
Terminated |
NCT05915897 -
Whole Blood Biospecimen Collection for Subjects With Chronic Granulomatous Disease (CGD)
|
||
Completed |
NCT00001317 -
A Phase IV Study of Recombinant Human Gamma Interferon in Patients With Chronic Granulomatous Diseases of Childhood
|
Phase 4 | |
Completed |
NCT03548818 -
Role of Interferon-gamma 1-b (IFN-γ) on Cells of the Innate Immune System: Functional, Biochemical and Gene Expression Studies in Patients With Chronic Granulomatous Disease
|
||
Recruiting |
NCT01821781 -
Immune Disorder HSCT Protocol
|
Phase 2 | |
Completed |
NCT00578643 -
Matched Unrelated or Non-Genotype Identical Related Donor Transplantation For Chronic Granulomatous Disease
|
Phase 2 | |
Terminated |
NCT00006054 -
Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies
|
N/A | |
Enrolling by invitation |
NCT06253507 -
pCCLCHIM-p47 (Lentiviral Vector Transduced CD34 Plus Cells) in Patients With p47 Autosomal Recessive Chronic Granulomatous Disease (AR-CGD)
|
Phase 1/Phase 2 |