Ignite Creation Date:
2024-05-05 @ 12:11 PM
Last Modification Date:
2024-10-26 @ 9:21 AM
Study NCT ID:
NCT00263237
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2005-12-07
Brief Title:
STA-5326 Meslylate to Treat Gut Inflammation Associated With Common Variable Immunodeficiency
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Pilot Study of Safety and Efficacy of the Oral IL-1223 Inhibitor STA-5326 Mesylate for Symptomatic Gastrointestinal Inflammation Associated With Common Variable Immunodeficiency
Status:
COMPLETED
Status Verified Date:
2008-07-23
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will determine whether an experimental medicine STA-5326 mesylate is safe to use in patients with common variable immunodeficiency CVID who have inflammation of the gut It will also determine if patients who take this drug show improvement in their symptoms decrease in inflammatory chemicals in the gut changes in their immune cells and improvement in how their gut is functioning to absorb food
Patients between 18 and 75 years of age with CVID and chronic diarrhea or involuntary weight loss of more than 5 percent of their past body weight over the past 12 months may be eligible for this study Candidates are screened with a review of their medical records a medical history and physical examination blood urine and stool tests chest x-rays and skin test for exposure to tuberculosis and a hydrogen breath test For the latter breath samples are collected before and every 20 minutes for 2 hours after the subject drinks a sugar solution This test determines the digestive effects of bacteria in the upper intestine Samples are collected by having the subject blow into a balloon
Participants undergo the following tests and procedures
Immune System and Gastrointestinal Evaluation
48-hour stool fat collection measures the amount of undigested fat in the stool Subjects keep a diary of what they eat for a 48-hour period At the beginning of the 48 hours they take two dye capsules and then take another two capsules 48 hours later They collect a stool sample when they pass the second set of capsules in their bowel movement An additional 24-hour stool collection is tested for loss of protein in the stool
D-xylose absorption test measures the ability of the gut to absorb nutrients Subjects drink a solution of d-xylose a sugar substitute Blood samples are collected before and 1 hour after drinking the solution
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 flexible lighted tube is advanced through the rectum to evaluate the colon
Treatment Period Study days 1 to 57
Physical examination - study days 1 8 15 29 43 and 57
Blood samples to test the levels of STA-5326 in the blood On study days 1 and 57 samples are collected before the medication dose and 1 2 4 6 and 8 hours after the dose on day 29 one sample is collected before the medication dose
Blood samples for routine safety testing - study days 1 8 15 29 43 and 57
Medication history - study days 1 8 15 29 43 and 57
Interview about pain discomfort and well being - study days 1 8 15 29 43 and 57
Pregnancy test for women who can become pregnant - study days 15 43 and 57
D-xylose absorption test - study days 29 and 57
Electrocardiogram - study days 29 and 57
Urine test - study days 29 and 57
Blood test for research on immune cells - study day 57
Repeat endoscopies and studies of gut function 24- and 48-hour stool collections
Follow-up period Day 85 and day 113
-Physical examination blood tests medication history questions about pain discomfort and well being
Patients between 18 and 75 years of age with CVID and chronic diarrhea or involuntary weight loss of more than 5 percent of their past body weight over the past 12 months may be eligible for this study Candidates are screened with a review of their medical records a medical history and physical examination blood urine and stool tests chest x-rays and skin test for exposure to tuberculosis and a hydrogen breath test For the latter breath samples are collected before and every 20 minutes for 2 hours after the subject drinks a sugar solution This test determines the digestive effects of bacteria in the upper intestine Samples are collected by having the subject blow into a balloon
Participants undergo the following tests and procedures
Immune System and Gastrointestinal Evaluation
48-hour stool fat collection measures the amount of undigested fat in the stool Subjects keep a diary of what they eat for a 48-hour period At the beginning of the 48 hours they take two dye capsules and then take another two capsules 48 hours later They collect a stool sample when they pass the second set of capsules in their bowel movement An additional 24-hour stool collection is tested for loss of protein in the stool
D-xylose absorption test measures the ability of the gut to absorb nutrients Subjects drink a solution of d-xylose a sugar substitute Blood samples are collected before and 1 hour after drinking the solution
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 flexible lighted tube is advanced through the rectum to evaluate the colon
Treatment Period Study days 1 to 57
Physical examination - study days 1 8 15 29 43 and 57
Blood samples to test the levels of STA-5326 in the blood On study days 1 and 57 samples are collected before the medication dose and 1 2 4 6 and 8 hours after the dose on day 29 one sample is collected before the medication dose
Blood samples for routine safety testing - study days 1 8 15 29 43 and 57
Medication history - study days 1 8 15 29 43 and 57
Interview about pain discomfort and well being - study days 1 8 15 29 43 and 57
Pregnancy test for women who can become pregnant - study days 15 43 and 57
D-xylose absorption test - study days 29 and 57
Electrocardiogram - study days 29 and 57
Urine test - study days 29 and 57
Blood test for research on immune cells - study day 57
Repeat endoscopies and studies of gut function 24- and 48-hour stool collections
Follow-up period Day 85 and day 113
-Physical examination blood tests medication history questions about pain discomfort and well being
Detailed Description:
The purpose of this study is to assess the toxicity of the oral IL-1223 inhibitor STA-5326 mesylate in subjects with common variable immunodeficiency CVID and associated symptomatic gastrointestinal inflammation Common variable immunodeficiency is a clinically heterogeneous disorder characterized by decreased serum immunoglobulin IgG and IgA levels In addition to chronic or recurrent pyogenic sino-pulmonary infections many patients develop non-infectious gastrointestinal manifestations that can be disabling or fatal 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
Recently gut inflammation complicating CVID has been characterized as a Th1 inflammatory response with excess cytokine production associated with diarrhea and weight loss as well as reduced D-xylose absorption and steatorrhea This protocol represents the first attempt to test specific anti-IL-12 therapy in this patient group it has been previously shown that therapy targeted to IL-1223 successfully treated the Th1 gut inflammation of Crohns disease While this protocol is designed to measure the safety of STA-5326 mesylate in CVID patients it will also measure effects on symptoms gut function expression of immune cell surface markers and production of cytokines from blood and gut mucosal mononuclear cells
CVID patients with gastrointestinal symptoms of malabsorption maldigestion and chronic diarrhea will be enrolled into this study Subjects up to a total of 10 individuals will receive STA-5326 mesylate 100 mg per os PO once daily QD equivalent to 70 mg STA-5326 free base for 8 weeks Subjects will have pretreatment and end-of-study procedures including upper and lower endoscopies to measure changes in immune responses and physiologic measures of gut function as well as routine safety monitoring throughout the treatment period Variables will include safety adverse event rate clinical weight stool frequency results of gut absorption tests and laboratory lymphocyte and cytokine assays parameters for descriptive summary statistical analysis n mean median standard deviation minimum and maximum range
Recently gut inflammation complicating CVID has been characterized as a Th1 inflammatory response with excess cytokine production associated with diarrhea and weight loss as well as reduced D-xylose absorption and steatorrhea This protocol represents the first attempt to test specific anti-IL-12 therapy in this patient group it has been previously shown that therapy targeted to IL-1223 successfully treated the Th1 gut inflammation of Crohns disease While this protocol is designed to measure the safety of STA-5326 mesylate in CVID patients it will also measure effects on symptoms gut function expression of immune cell surface markers and production of cytokines from blood and gut mucosal mononuclear cells
CVID patients with gastrointestinal symptoms of malabsorption maldigestion and chronic diarrhea will be enrolled into this study Subjects up to a total of 10 individuals will receive STA-5326 mesylate 100 mg per os PO once daily QD equivalent to 70 mg STA-5326 free base for 8 weeks Subjects will have pretreatment and end-of-study procedures including upper and lower endoscopies to measure changes in immune responses and physiologic measures of gut function as well as routine safety monitoring throughout the treatment period Variables will include safety adverse event rate clinical weight stool frequency results of gut absorption tests and laboratory lymphocyte and cytokine assays parameters for descriptive summary statistical analysis n mean median standard deviation minimum and maximum range
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 06-I-0037 | None | None | None |