STA-5326 Meslylate to Treat Gut Inflammation Associated With Common Variable Immunodeficiency

NCT00263237 | Completed Phase 1

• 2 other identifiers: 06003706-I-0037
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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

Conditions

Common Variable Immunodeficiency

Keywords

T Cell; Lymphocyte; Lamina Propria; Malabsorption; Colonoscopy; Common Variable Immunodeficiency; CVID; Gastrointestinal Inflammation

Interventions

STA-5326 DRUG

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A subject is eligible for the study if all of the following criteria are met:
• Has given written informed consent prior to screening.
• Is male or female aged 18 through 75 years.
• Has CVID diagnosed definitively prior to screening (based on the IUIS criteria).
• Has a documented, unintended loss of greater than 5% of their body weight over the last year or requires nutritional supplements to maintain his/her body weight OR has chronic diarrhea defined as a complaint of liquid stools for at least 4 consecutive weeks (and an output of greater than 200 g stool/24hr on a diet of at least 1600 calories with 60 g fat.)
• If taking oral antibiotics chronically, must have used a stable dose of the antibiotic continuously for at least 2 weeks prior to start of screening period.
• Not taking any potential CYP3A4 inhibitors/inducers (e.g., macrolide antibiotics, HIV protease inhibitors, antifungals, grapefruit juice, St. John's Wort).

You may not qualify if:

• A subject is excluded from the study if any of the following criteria are met:
• General Criteria:
• Has any clinically significant disease (e.g., renal, hepatic, neurological, cardiovascular, pulmonary, endocrinologic, psychiatric, hematologic, urologic, or other acute or chronic illness) that in the opinion of the investigator would make the subject an unsuitable candidate for this trial.
• Is a woman who has a positive serum pregnancy test or who is breast-feeding.
• Is a woman of childbearing potential or a man who does not agree to use two forms of contraception during the course of the study and follow-up period.
• Has hypersensitivity to any of the components of STA 5326 mesylate drug product.
• Has any of the following clinical chemistry values:
• AST greater than 2.5 x upper limit of normal (ULN).
• ALT greater than 2.5 x ULN.
• Serum bilirubin greater than 1.5 x ULN.
• Serum creatinine greater than 1.5 x ULN.
• Alkaline phosphatase greater than 2.5 x ULN.
• Has a hemoglobin level less than 9 g/dL or hematocrit less than 30%.
• Has a Prothromin Time INR greater than 1.3 or a Partial Thromboplastin Time greater than 3 sec compared to control value.
• Has the following cell counts (cells/microliter):

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Hayes MP, Wang J, Norcross MA. Regulation of interleukin-12 expression in human monocytes: selective priming by interferon-gamma of lipopolysaccharide-inducible p35 and p40 genes. Blood. 1995 Jul 15;86(2):646-50.

  PMID: 7605994 BACKGROUND

• DeKruyff RH, Fang Y, Umetsu DT. Corticosteroids enhance the capacity of macrophages to induce Th2 cytokine synthesis in CD4+ lymphocytes by inhibiting IL-12 production. J Immunol. 1998 Mar 1;160(5):2231-7.

  PMID: 9498762 BACKGROUND

• Larsson S, Linden M. Effects of a corticosteroid, budesonide, on production of bioactive IL-12 by human monocytes. Cytokine. 1998 Oct;10(10):786-9. doi: 10.1006/cyto.1998.0362.

  PMID: 9811532 BACKGROUND

MeSH Terms

Conditions

Common Variable Immunodeficiency; Malabsorption Syndromes

Interventions

apilimod

Condition Hierarchy (Ancestors)

Immunologic Deficiency Syndromes; Immune System Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: December 7, 2005
• First Posted: December 7, 2005
• Study Start: December 2, 2005
• Study Completion: July 23, 2008
• Last Updated: July 2, 2017

Record last verified: 2008-07-23

Locations

US (1)