Clinical Trial: Raltegravir for HAM/TSP

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Pilot Study of Raltegravir, an Integrase Inhibitor, in Human T-Cell Lymphotrophic Virus-1(HTLV-1) Associated Myelopathy, Tropical Spastic Paraparesis (HAM/TSP)

Brief Summary:

Background:

- Human T-cell lymphotropic virus type 1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an infection of the spinal cord. The infection is caused by a virus that has been known to cause cancers like leukemia and lymphoma. It causes a weakening of the legs. Researchers want to see if raltegravir, a drug for treating human immunodeficiency virus (HIV), can be used to treat HAM/TSP. They will see if the drug can reduce the amount of virus in the blood of people with HAM/TSP.

Objectives:

- To see if raltegravir can reduce the viral load of people with HAM/TSP.

Eligibility:

- Individuals at least 18 years of age who have HAM/TSP.

Design:

  • Participants will be screened with a physical exam and medical history. Blood samples will be collected. Imaging studies will be performed. A lumbar puncture will also be taken.
  • Participants will take the study drug twice a day for 6 months. They will note each dose in a study diary, as well as any side effects.
  • At the 6-month visit, participants will stop taking the study drug. They will have a physical exam and blood samples, as well as other tests.
  • Participants will have two further exams 9 months and 15 months after starting the study drug. They will have a physical exam and blood samples, as well as other tests.

Detailed Summary:

Objective:

In this pilot study, we wish to determine the effects of Raltegravir, a clinically approved HIV-1 integrase inhibitor, on HTLV-1 proviral load (PVL) in patients with HTLV-1 associated myelopathy / tropical spastic paraparesis (HAM/TSP). We will also provide safety and tolerability information on Raltegravir use in this condition and examine the correlation of immune activation markers in HAM/TSP with the effects of Raltegravir on the PVL.

Study population:

HAM/TSP, a relentlessly progressive and disabling myelopathy, occurs in up to 3% of HTLV-1 infected subjects. It results from immune-mediated bystander damage of the neural tissues in association with an elevated PVL. In fact, a high PVL is considered to be the main risk factor for developing HAM/TSP as the risk of disease rises exponentially once the PVL exceeds 1 %. Currently there is no effective treatment for HAM/TSP.

There is evidence that active HTLV-1 replication, through the retroviral life cycle with new virus integration, is occurring in vivo and contributes to the total HTLV-1 PVL in infected subjects. Recently it was shown that Raltegravir could inhibit cell-free and cell-to-cell transmission of HTLV-1 in vitro. Given the substantial clinical experience with its use in HIV-1 infection and particularly its excellent safety profile, this agent is an attractive therapeutic option for patients with HAM/TSP, either alone or in combination with immunomodulatory treatment. In this pilot study we wish to determine the effects of Raltegravir in vivo on HTLV-1 PVL and immune activation markers in patients with HAM/TSP.

Design:

In this 15 months single center, si
Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)

Current Primary Outcome: Reduction of HTLV-1 Proviral load in HAM/TSP patients [ Time Frame: 15 months ]

Original Primary Outcome: Determine the effect of Raltegravir on HTLV-1 Proviral load in HAM/TSP patients [ Time Frame: 6 months ]

Current Secondary Outcome:

Original Secondary Outcome:

Information By: National Institutes of Health Clinical Center (CC)

Dates:
Date Received: May 21, 2013
Date Started: May 6, 2013
Date Completion: December 30, 2018
Last Updated: May 12, 2017
Last Verified: December 12, 2016