Clinical Trial: Trial to Assess Effect of Raltegravir on HTLV-1 Proviral Load

Study Status: Recruiting
Recruit Status: Unknown status
Study Type: Interventional

Official Title: Phase II Trial to Assess Effect of Raltegravir on HTLV-1 Proviral Load

Brief Summary: 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.

Detailed Summary: 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.
Sponsor: Washington University School of Medicine

Current Primary Outcome: Effects of raltegravir on HTLV-1 provirus load in asymptomatic individuals [ Time Frame: 8 wks ]

Measured by DNA PCR from peripheral blood mononuclear cell DNA at days 0, 1, 8, 15, 29, 43, and 56.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Effects of raltegravir on proviral load in CD4+CD25+, CD4+CD25-, and CD8+ cell populations [ Time Frame: 8 wks ]
    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 ]
    1. 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
    2. 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 ]
    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 ]
    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 ]
    Assessed by physical exam, CBC, and serum chemistries on days 29 and 57 and


Original Secondary Outcome: Same as current

Information By: Washington University School of Medicine

Dates:
Date Received: January 25, 2012
Date Started: January 2012
Date Completion: December 2014
Last Updated: June 14, 2012
Last Verified: June 2012