Phase II Trial to Assess Effect of Raltegravir on HTLV-1 Proviral Load
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Effects of raltegravir on HTLV-1 provirus load in asymptomatic individuals
研究概览
简要总结
This is a study of the effect of raltegravir on human T-cell leukemia virus type 1 (HTLV-1) viral load in asymptomatic patients. The study will enroll 14 subjects for a period of 2 months of treatment and 1 month of followup. The study will assess the effect of raltegravir on virus load in peripheral blood lymphocytes, level of virus gene expression, and sites of viral integration.
详细描述
About 5% of HTLV-1 infected individuals develop lymphoma or myelopathy. High levels of virus replication are predictive of disease development. HTLV-1 exhibits lower levels of variation than HIV-1, suggesting that drug resistance is less likely to occur. Raltegravir was shown to inhibit HTLV-1 integration and replication in culture using concentrations achievable with the approved dose used in HIV-1 infected patients. Currently, no treatment is recommended for asymptomatic infected individuals.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented HTLV-1 infection: documentation may be serologic assay (ELISA, Western blot) and confirmed to be HTLV-1 rather than HTLV-2 by differential Western blot (e.g. Genelabs Diagnostics HTLV Blot 2.4) or PCR.
- •Adequate hematologic function within 14 days before enrollment: ANC > 1000 cells/mm3, platelet count > 75,000 cells/mm
- •Adequate hepatic function, transaminase < 3 times the upper limit of normal; bilirubin < 2.
- •Creatinine < 2.0
- •Karnofsky Performance Status at least 70
- •Age at least
- •Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
- •Female patients of child bearing potential must have a negative pregnancy test within 72 hrs of initiation of therapy. Female patients are either post-menopausal or surgically sterilized or willing to use two acceptable methods of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) during the study. Male patients must agree to use two acceptable methods for contraception for the duration of the study. Women must avoid pregnancy and men avoid fathering children while in the study.
- •Inclusion of Women and Minorities: Both men and women and members of all races and ethnic groups are eligible for this trial.
排除标准
- •Acute active infection requiring therapy. Chronic therapy with potentially myelosuppressive agents is allowed provided that entry hematologic criteria are met.
- •Women who are pregnant or breastfeeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
- •Patient has received other investigational drugs with 14 days before enrollment
- •Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
研究组 & 干预措施
Raltegravir
Treatment with raltegravir for 8 wks
干预措施: Raltegravir (Drug)
结局指标
主要结局
Effects of raltegravir on HTLV-1 provirus load in asymptomatic individuals
时间窗: 8 wks
Measured by DNA PCR from peripheral blood mononuclear cell DNA at days 0, 1, 8, 15, 29, 43, and 56.
次要结局
- Effects of raltegravir on number of LTR circles and level of proviral RNA expression in PBMCs(8 wks)
- Effects of raltegravir on proviral load in CD4+CD25+, CD4+CD25-, and CD8+ cell populations(8 wks)
- Effect of raltegravir on viral integration sites(8 wks)
- Effects of raltegravir on viral integrase gene or other viral sequence changes(8 wks)
- Tolerance of raltegravir in HTLV-1 infected individuals(8 wks)