Teriflunomide in HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis
- Registration Number
- NCT04799288
- Brief Summary
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.
- Detailed Description
Study Description:
In this single center, single arm, open label, baseline versus treatment pilot clinical trial, sixteen subjects with HAM/TSP will receive teriflunomide 14mg by mouth once a day in an initial 9 month treatment phase, followed by a 3 month post treatment follow-up phase. Outcome measures will be collected every 3 months for the duration of the study.
Objectives:
We will determine the effects of teriflunomide, an FDA approved drug for the treatment of relapsing remitting multiple sclerosis that inhibits de novo pyrimidine synthesis, on immune activation markers in patients with HAM/TSP and the correlation of these with virological, radiological and clinical measures of disease burden .
Endpoints:
The primary outcome measure is ex vivo spontaneous lymphoproliferation in HAM/TSP patients receiving teriflunomide. Secondary outcome measures will include determination of immune activation patterns of PBMC and CSF using multicolor flow cytometric analysis and HTLV-I proviral load in blood and CSF. Safety and tolerability of teriflunomide will be assessed by tabulation of adverse events, clinical exam, standardized neurological disability scales (EDSS, IPEC, HAQ-DI), MR imaging of brain and spinal cord and clinical laboratory studies.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 24
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Teriflunomide Teriflunomide Teriflunomide 14 mg daily
- Primary Outcome Measures
Name Time Method ex vivo spontaneous lymphoproliferation in HAM/TSP patients receiving teriflunomide Percent change between Day 0 and month 9 of spontaneous proliferation. ex vivo spontaneous lymphoproliferation of HAM/TSP patients receiving teriflunomide and multicolor flow cytometric analysis of immune activation markers in both PBMCs and CSF
- Secondary Outcome Measures
Name Time Method Tabulation of adverse events at each visit 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 between month -3 and month 9 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) at month 9 and compared to Day 0 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 at month 9 and compared to month -3 HTLV-1 proviral load is a measure of the percent of infected cells and previous data suggests a correlation with disease activity.
Change in IPEC score at month 9 and compared to Day 0 This is a first in HAM/TSP pilot study using teriflunomide thus important to monitor for any unexpected events related to worsening of clinical measures.
Change in EDSS score at month 9 and compared to Day 0 This is a first in HAM/TSP pilot study using teriflunomide thus important to monitor for any unexpected events related to worsening of clinical measures.
Change in 25-foot timed walk at month 9 and compared to Day 0 This is a first in HAM/TSP pilot study using teriflunomide thus important to monitor for any unexpected events related to worsening of clinical measures.
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States