Interferon-gamma To Treat Chronic HCV Infection

干扰素-γ治疗慢性丙型肝炎病毒感染

• 批准号: 6321044
• 负责人: Andrew J. Muir
• 金额: $ 6.62万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-21 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6321044
• 关键词: adult human (21+); biopsy; chronic disease /disorder; clinical trial phase I; cytokine; hepatitis C; hepatitis C virus; histology; human subject; human therapy evaluation; immunotherapy; interferon gamma; liver disorder chemotherapy; microorganism disease chemotherapy; patient oriented research; protein biosynthesis; quality of life

DESCRIPTION (adapted from the application) Current treatment options for chronic hepatitis C infection remain limited and unsatisfactory. Treatment with interferon-alpha and ribavirin leads to a sustained response in the minority of patients, and many patients may not be eligible for treatment due to side effects associated with these medications. Other treatment options are clearly necessary for chronic hepatitis C infection. A major complication of chronic hepatitis C infection is fibrogenesis, ultimately leading to development of cirrhosis. Animal models have demonstrated that interferon-gamma reduces fibrogenesis through its effect on stellate cells. A recent report in patients with idiopathic pulmonary fibrosis found that interferon-gamma was well-tolerated and led to improved pulmonary function, ostensibly due to a reduction in fibrogenesis. Given these data, we postulate not only that interferon-gamma will be effective for treatment of hepatitis C mediated fibrogenesis, but also that it will be safe. We have therefore proposed a phase I study to assess the effectiveness of interferon-gamma in twenty patients with chronic hepatitis C infection. The patients will include those who have failed previous therapy with interferon-alpha or are not candidates for interferon-alpha therapy. Men or women 18 years of age or older are eligible. Other inclusion criteria are serum positive for hepatitis C virus by PCR; liver biopsy consistent with chronic hepatitis and with a fibrosis score of at least one on the Knodell scale; compensated liver disease; and informed, written consent obtained prior to entry. All patients will receive 200 micrograms of interferon-gamma three times a week for twelve months. Patients will undergo liver biopsy prior to treatment and at the end of treatment. Safety and tolerance will be evaluated at weeks 1, 2, 4, 8 and then every 4 weeks during treatment and at weeks 4 and 12 following the completion of therapy. Serum HCV-RNA will be evaluated prior to initiating therapy and at the end of therapy. The primary endpoint of this study will be the histological response of patients with chronic hepatitis C infection to treatment with interferon-gamma. Secondary endpoints include the biochemical response, inflammatory and regulatory cytokine levels, and quality of life during treatment.

描述（改编自应用程序） 目前慢性丙型肝炎感染的治疗选择仍然有限， 不满意。使用干扰素-α和利巴韦林治疗会导致 少数患者有持续反应，而许多患者可能不会 由于这些药物相关的副作用而有资格接受治疗。 对于慢性丙型肝炎，其他治疗方案显然是必要的 感染。慢性丙型肝炎感染的一个主要并发症是 纤维化，最终导致肝硬化的发展。动物模型 已证明干扰素-γ 通过其作用减少纤维形成 星状细胞上。最近关于特发性肺病患者的报告 纤维化研究发现，干扰素-γ具有良好的耐受性，并可改善纤维化 肺功能，表面上是由于纤维生成的减少。鉴于这些 根据数据，我们假设干扰素伽马不仅对 治疗丙型肝炎介导的纤维化，而且也表明它会是安全的。 因此，我们提出了一项第一阶段研究来评估其有效性 二十名慢性丙型肝炎感染患者的干扰素γ。这 患者将包括那些先前治疗失败的患者 干扰素-α 或 不是干扰素-α 治疗的候选者。男性或 18 岁或以上的女性有资格。其他纳入标准是血清 PCR 检测丙型肝炎病毒呈阳性；肝活检符合慢性 肝炎且 Knodell 量表纤维化评分至少为 1； 代偿性肝病；并事先获得知情的书面同意 入口。所有患者将接受3次200微克干扰素-γ治疗 十二个月一周。患者在治疗前将接受肝活检 以及在治疗结束时。安全性和耐受性将在第 1 周进行评估， 治疗期间第 2、4、8 次，然后每 4 周一次以及随后的第 4 周和第 12 周 完成治疗。在开始之前将评估血清 HCV-RNA 治疗和治疗结束时。 这项研究的主要终点是组织学反应 慢性丙型肝炎感染患者接受干扰素-γ治疗。 次要终点包括生化反应、炎症和 调节细胞因子水平和治疗期间的生活质量。