A MULTICENTER, PARALLEL, RANDOMIZED, CONTROLLED, ONE-YEAR STUDY OF BOVINE COL

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。该研究是一项多中心II期临床试验，旨在确定500克/天口服牛I型胶原蛋白（CI）是否会改善弥漫性系统性硬化症（SSc）。本研究采用随机、分层（针对病程）、双盲、安慰剂对照的临床试验设计。共有10个参与中心。有9个临床中心和3个核心。患者将被分为两组：一组病程<= 3年，另一组病程3 ~ 10年。本研究将验证口服CI可改善SSc的假设，以及口服饲喂牛CI可诱导弥漫性SSc患者口服耐受或下调PBMC对CI a链的反应性的假设。168例弥漫性SSc <= 1年或病程<= 10年的患者将被分层和随机分配，每天接受安慰剂[2 ml 0.1 M乙酸（HAc）]或500¿¿g牛CI，为期12个月。患者将接受筛查、基线、4、8、12和15个mo的改良罗德曼皮肤评分（MRSS）测量作为主要临床结果变量，硬皮病健康评估问卷(SHAQ)-一份简短的36份问卷，医生整体评估、患者整体评估、血压、体重和血清肌酐测定作为次要临床结果测量。对于退出研究大于或等于6个月，小于或等于11个月的患者，这些主要和次要临床结局指标将在退出研究时以及在12个月和15个月时获得。患者将在基线、0个月和12个月或退出研究和12个月时测量FVC和DLCO，作为次要临床结果参数。将在口服牛CI治疗前后12个月获得血清和PBMC。PBMC将在有牛a1 (I)和a2 (I)链和天然牛CI的情况下进行培养。ELISA法检测血清和PBMC上清液中IFN？和IL-10，基线和12个月。IFN减少？或口服CI后由链刺激的PBMC产生IL-10将是主要的免疫学结果变量。将在基线和12个月时测量SSc患者血清中的IL-2R水平，作为次要免疫学结果变量。

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.