Background:
HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a rare, progressive disease. It occurs in some people infected with the HTLV-1 virus. It leads to weakness in the lower limbs and other serious problems. It has no treatment. Teriflunomide is a drug used to treat multiple sclerosis. It reduces immune cells that make the disease worse. Researchers want to learn if this drug can help people with HAM/TSP.
Objective:
To learn the effects, immune response, safety, and tolerability of teriflunomide in people with HAM/TSP.
Eligibility:
Adults ages 18 and older with HAM/TSP.
Design:
Participants will be screened under protocol 98-N-0047.
Participants will have a medical history. They will have physical and neurological exams. They will have blood and urine tests.
Participants will take 1 tablet of the study drug once a day for 9 months. They will keep a drug diary.
Participants will have lymphapheresis. For this, blood is drawn from a needle in one arm. A machine divides the blood into red cells, plasma, and white cells. The white cells are removed. The plasma and red cells are returned to the participant through a needle in the other arm.
Participants will have lumbar punctures ( spinal taps ). For this, a thin needle is inserted into the spinal canal in the lower back. Spinal fluid is removed.
Participants will have magnetic resonance imaging (MRI) of the brain and spine. The MRI scanner is a metal cylinder surrounded by a strong magnetic field. During the MRI, participants will lie on a table that can slide in and out of the scanner.
Participation will last for 15 months.
18 years or older
Diagnosis of HAM/TSP as defined by WHO criteria, including a positive HTLV-1 EIA and confirmatory Western Blot.
Enrolled in 98-N-0047
Patient must be willing and able to comply with all the aspects of trial design and follow-up.
Alternative diagnoses that can explain neurological disability
History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial or interfere with participation for the full duration of the trial; or not in the best interest of the subject to participate, in the opinion of the treating investigator
Severe immunodeficiency, bone marrow disease, or severe, uncontrolled infections.
Liver dysfunction, as indicated by baseline aspartate aminotransferase (AST) or alanine or alanine aminotransferase (ALT) greater than 2 times the upper limit of normal
Single group
Teriflunomide
DrugTeriflunomide 14mg will be administered orally as 1 tablet once daily during the 9-month treatment phase of the study.
ex vivo spontaneous lymphoproliferation in HAM/TSP patients receiving teriflunomide
ex vivo spontaneous lymphoproliferation of HAM/TSP patients receiving teriflunomide and multicolor flow cytometric analysis of immune activation markers in both PBMCs and CSF
Tabulation of adverse events
This is a first in HAM/TSP pilot study using teriflunomide thus important to monitor for any unexpected events related to worsening of disease laboratory and clinical measures.
Percent change between CD8+ and CD4+ cells in the CSF
CD8 cells are thought to be immunopathogenic and drive the immune response. In vitro studies have shown a reduction of CD8+ and CD4+ cells in the presences of teriflunomide.
HTLV-1 proviral load in the peripheral blood mononuclear cells (PBMCs)
HTLV-1 proviral load is a measure of the percent of infected cells and previous data suggests a correlation with disease activity.
HTLV-1 proviral load in the CSF cells
HTLV-1 proviral load is a measure of the percent of infected cells and previous data suggests a correlation with disease activity.
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