This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This study is a multi-center Phase II clinical trial to determine whether oral bovine type I collagen (CI) at 500 g/day will improve diffuse systemic sclerosis (SSc). The study employs a randomized, stratified (for disease duration), double-blind, placebo-controlled, clinical trial experimental design. There are 10 participating centers. There are 9 clinical centers and 3 cores. Patients will be stratified into groups: one with disease duration <= 3 yr and one with disease duration of >3 to and including 10 yrs. This proposal will test the hypothesis that oral CI will induce improvement in SSc, and that oral feeding of bovine CI will induce oral tolerance or downregulation of PBMC reactivity to CI a chains in patients with diffuse SSc. 168 patients with diffuse SSc of <= yrs or > 3 <= 10 years duration will be stratified and randomized to receive daily placebo [2 ml 0.1 M acetic acid (HAc)] or 500 g bovine CI for 12 months. Patients will have screening, baseline, 4, 8, 12, and 15 mo. measurements of modified Rodnan skin score (MRSS) as a primary clinical outcome variable and Scleroderma Health Assessment Questionnaire (SHAQ)-a, short form 36 questionnaire, Physician's Global Assessment, Patient's Global Assessment, blood pressure, weight and serum creatinine determinations as secondary clinical outcome measures. For patients dropping out of the study greater than or equal to 6 months and less than or equal to 11 months, these primary and secondary clinical outcome measures will be obtained at the time of drop-out and at 12 and 15 months. Patients will have FVC and DLCO measured at baseline, 0 and at 12 months or at dropout from the study and at 12 months as secondary clinical outcome parameters. Sera and PBMC will be obtained before and after 12 months treatment with oral bovine CI. The PBMC will be cultured with and without bovine a1 (I) and a2 (I) chains and native bovine CI. The sera and PBMC supernatants will be analyzed by ELISA for IFN? and IL-10, at baseline and 12 months. Decreases in IFN? or IL-10 production by a chain-stimulated PBMC after oral CI will be the primary immunology outcome variable. IL-2R levels will be measured in serum of SSc patients at baseline and 12 months as a secondary immunology outcome variable.
Showing the most recent 10 out of 203 publications
