HAM/TSP Clinical Trial
Official title:
Phase I/II Study of Teriflunomide in HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis
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.
| Status | Recruiting |
| Enrollment | 24 |
| Est. completion date | August 31, 2025 |
| Est. primary completion date | August 31, 2025 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 120 Years |
| Eligibility | - INCLUSION CRITERIA: In order to be eligible to participate in this study, an individual must meet all of the following criteria: - 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. - Negative QuantiFERON-TB gold, or completion of latent tuberculosis infection treatment, per CDC and National TB Controllers Association recommendations in the event of a positive test result --In the event of an indeterminant result, the test will be repeated. Should two consecutive tests yield indeterminant results, a chest x-ray will be performed to rule out radiographic evidence of a latent TB infection. Negative imaging will enable the subject to qualify for participation in the study. - Ability to take oral medication and be willing to adhere to the protocol regimen - Patients must be able to provide informed consent - If able to become pregnant or to father a child, patient must agree to commit to the use of a reliable/accepted method of birth control (i.e. hormonal contraception (birth control pills, injected hormones, vaginal ring), intrauterine device, barrier methods with spermicide (diaphragm with spermicide, condom with spermicide) or surgical sterilization (hysterectomy, tubal ligation, or vasectomy) for the duration of the treatment arm of the study and for two years following cessation of treatment with teriflunomide. EXCLUSION CRITERIA: An individual who meets any of the following criteria will be excluded from participation in this study: - 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 - Positive serological evidence of HIV, HTLV-II, Hepatitis B or C - Treatment with immunomodulatory/immunosuppressive therapy is exclusionary except in the cases below: - current use of topical steroids - <= 10 mg of prednisone usage within three months prior to administration of study drug. - Pregnant or lactating women. - Treatment with other investigational drugs within 6 months before enrollment - Known hypersensitivity to teriflunomide or leflunomide - Concomitant treatment with leflunomide |
| Country | Name | City | State |
|---|---|---|---|
| United States | National Institutes of Health Clinical Center | Bethesda | Maryland |
| Lead Sponsor | Collaborator |
|---|---|
| National Institute of Neurological Disorders and Stroke (NINDS) |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | Percent change between Day 0 and month 9 of spontaneous proliferation. | |
| Secondary | 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. | at each visit | |
| Secondary | 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. | between month -3 and month 9 | |
| Secondary | 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. | at month 9 and compared to Day 0 | |
| Secondary | 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. | at month 9 and compared to month -3 | |
| Secondary | Change in IPEC score | 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. | at month 9 and compared to Day 0 | |
| Secondary | Change in EDSS score | 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. | at month 9 and compared to Day 0 | |
| Secondary | Change in 25-foot timed walk | 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. | at month 9 and compared to Day 0 |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT04830319 -
Pilates Method in People With HAM/TSP
|
N/A |