Trial to Assess Effect of Raltegravir on HTLV-1 Proviral Load
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.
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Trial to Assess Effect of Raltegravir on HTLV-1 Proviral Load|
- Effects of raltegravir on HTLV-1 provirus load in asymptomatic individuals [ Time Frame: 8 wks ] [ Designated as safety issue: No ]Measured by DNA PCR from peripheral blood mononuclear cell DNA at days 0, 1, 8, 15, 29, 43, and 56.
- Effects of raltegravir on proviral load in CD4+CD25+, CD4+CD25-, and CD8+ cell populations [ Time Frame: 8 wks ] [ Designated as safety issue: No ]Measured by real time PCR with DNA from sorted peripheral blood mononuclear cell DNA at days 1, 8, 15, 29, 43, and 56.
- Effects of raltegravir on number of LTR circles and level of proviral RNA expression in PBMCs [ Time Frame: 8 wks ] [ Designated as safety issue: No ]
- Number of LTR circles measure by real time PCR on peripheral blood mononculear cell DNA at days 0, 1, 8, 15, 29, 43, and 56
- Level of Proviral RNA Expression in PBMCs measured by real time RT PCR on peripheral blood mononculear cell RNA at days 0, 1, 8, 15, 29, 43, and 56
- Effects of raltegravir on viral integrase gene or other viral sequence changes [ Time Frame: 8 wks ] [ Designated as safety issue: No ]Measured by automated sequence analysis of PCR amplified viral DNA obtained at days 0, 1, 8, 15, 29, 43, and 56
- Effect of raltegravir on viral integration sites [ Time Frame: 8 wks ] [ Designated as safety issue: No ]Measured by automated DNA analysis of oligonucleotide linked PCR amplified DNA from peripheral blood mononuclear cell DNA obtianed at days 0, 1, 8, 15, 29, 43,and 56
- Tolerance of raltegravir in HTLV-1 infected individuals [ Time Frame: 8 wks ] [ Designated as safety issue: Yes ]Assessed by physical exam, CBC, and serum chemistries on days 29 and 57 and
|Study Start Date:||January 2012|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
Treatment with raltegravir for 8 wks
Raltegravir 400 mg po bid
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.
|United States, California|
|University of California, San Francisco|
|San Francisco, California, United States, 94118|
|United States, Missouri|
|Washington University School of Medicine|
|St Louis, Missouri, United States, 63110|
|Principal Investigator:||Lee Ratner, MD PhD||Washington University School of Medicine|