Teriflunomide in HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04799288|
Recruitment Status : Recruiting
First Posted : March 16, 2021
Last Update Posted : January 4, 2022
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.
To learn the effects, immune response, safety, and tolerability of teriflunomide in people with HAM/TSP.
Adults ages 18 and older with HAM/TSP.
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.
|Condition or disease||Intervention/treatment||Phase|
|HAM/TSP||Drug: Teriflunomide||Phase 1 Phase 2|
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.
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 .
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.
Up to 24 adults with HAM/TSP, targeting at least 16 participants who complete 9 months of treatment with teriflunomide
Description of Sites/Facilities Enrolling Participants:
NIH Clinical Center
Description of Study Intervention:
Administration of teriflunomide 14mg daily for 9 months
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||16 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/II Study of Teriflunomide in HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis|
|Actual Study Start Date :||September 24, 2021|
|Estimated Primary Completion Date :||December 31, 2022|
|Estimated Study Completion Date :||December 31, 2022|
Teriflunomide 14 mg daily
Teriflunomide 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 [ Time Frame: 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
- HTLV-1 proviral load in the peripheral blood mononuclear cells (PBMCs) [ Time Frame: change from month 9 compared to baseline ]collect and analyze additional clinical and biological data relevant to the safety and tolerability of teriflunomide as well as clinical benefit.
- Change in IPEC score [ Time Frame: change from month 9 compared to baseline ]collect and analyze additional clinical and biological data relevant to the safety and tolerability of teriflunomide as well as clinical benefit.
- Change in EDSS score [ Time Frame: change from month 9 compared to baseline ]collect and analyze additional clinical and biological data relevant to the safety and tolerability of teriflunomide as well as clinical benefit.
- Change in 25-foot timed walk [ Time Frame: change from month 9 compared to baseline ]
- Tabulation of adverse events at each visit [ Time Frame: change from month 9 compared to baseline ]
- HTLV-1 proviral load in the CSF cells [ Time Frame: change from month 9 compared to baseline ]
- Percent change between baseline and month 9 of the percent of CD8+ cells in the CSF [ Time Frame: change from month 9 compared to baseline ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04799288
|Contact: Joan M Ohayon, C.R.N.P.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org|
|Principal Investigator:||Steven Jacobson, Ph.D.||National Institute of Neurological Disorders and Stroke (NINDS)|