Teriflunomide for Tropical Spastic Paraparesis
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)
No Placebo Group
Approved in 2 jurisdictions
Trial Summary
What is the purpose of this trial?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.
Do I need to stop my current medications to join the trial?The trial does not specify if you need to stop all current medications, but you cannot take immunomodulatory or immunosuppressive therapies, except for topical steroids or less than or equal to 10 mg of prednisone within three months before starting the study drug. You also cannot take leflunomide or other investigational drugs within 6 months before enrollment.
Is the drug Teriflunomide a promising treatment for Tropical Spastic Paraparesis?Based on the provided research articles, there is no specific information about Teriflunomide being used or showing promise as a treatment for Tropical Spastic Paraparesis. The articles mention other treatments like prednisone, methylprednisolone, and Combivir, but not Teriflunomide.23459
What safety data exists for Teriflunomide?Teriflunomide, also known as Aubagio, is approved for treating relapsing forms of multiple sclerosis. It has been studied extensively in clinical trials, showing it to be generally well tolerated. Common safety concerns include increased liver enzyme levels and potential teratogenicity, making it contraindicated in pregnant patients. Long-term safety data is limited, but insights can be drawn from its parent drug, leflunomide. Further research is needed to compare its safety and efficacy with other oral treatments.1011131415
What data supports the idea that the drug Teriflunomide for Tropical Spastic Paraparesis is an effective treatment?The available research does not provide any data on Teriflunomide for Tropical Spastic Paraparesis. The studies mentioned focus on other drugs and conditions, such as Parkinson's disease and progressive supranuclear palsy, but do not include information on Teriflunomide or its effectiveness for Tropical Spastic Paraparesis.167812
Eligibility Criteria
Adults over 18 with HAM/TSP, a rare disease linked to HTLV-1 virus causing lower limb weakness. Participants must be able to take oral meds, follow the trial design, and use reliable birth control if necessary. Excluded are those with severe immune or liver issues, other conditions that could affect results, or recent immunomodulatory drugs usage.Treatment Details
The study tests teriflunomide's effectiveness on HAM/TSP by monitoring effects and immune response over 9 months of daily tablet intake. It includes blood/urine tests, lymphapheresis (white cell removal), spinal taps for fluid analysis, and MRI scans of brain/spine.
1Treatment groups
Experimental Treatment
Group I: TeriflunomideExperimental Treatment1 Intervention
Teriflunomide 14 mg daily
Teriflunomide is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Aubagio for:
- Relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults
🇪🇺 Approved in European Union as Aubagio for:
- Relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults
Find a clinic near you
Research locations nearbySelect from list below to view details:
National Institutes of Health Clinical CenterBethesda, MD
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Who is running the clinical trial?
National Institute of Neurological Disorders and Stroke (NINDS)Lead Sponsor
References
Terguride in the treatment of Parkinson disease: preliminary experience. [2019]Terguride, a partial DA-agonist with both dopaminergic and antidopaminergic properties, was tested in 11 PD patients in the "decompensated" phase of the disease, characterized by the presence of dyskinesias and motor fluctuations. Combined treatment of these patients with 1 mg/day of terguride and stabilized doses of levodopa reduced the severity and frequency of dyskinesias and motor fluctuations along with a slight but significant improvement of parkinsonian clinical picture. The "modulatory" effect of terguride on DA receptors, in this experimental conditions, is discussed.
HTLV-1 and tropical spastic paraparesis. 1. Clinical features, pathology and epidemiology. [2019]The clinical profile of tropical spastic paraparesis (TSP), described in scattered tropical and subtropical territories over the past 30 years, has been more clearly defined since the discovery of its direct association with human T lymphotropic virus type 1 (HTLV-1). A chronic disease of adults, commoner in women, it usually presents as a progressive spastic paraparesis with sphincter disturbance, sometimes with backache and lower limb sensory disorder. Most cases are chair-bound within 10 years. Histology reveals a chronic lymphocytic meningomyelopathy, predominantly in the spinal cord, together with long tract demyelination and hyalinoid thickening of the media and adventitia of small blood vessels. Geographical areas of high prevalence of TSP are known in the Caribbean, South America, South Africa, southern Japan, the Seychelles and probably in India, and it is sparsely endemic elsewhere. The virus appears to exist within lymphocytes for long periods. Vertical transmission occurs postnatally, and sexual and transfusion infection are also recognized, but much remains to be clarified regarding its pathogenesis and epidemiology.
Tropical spastic paraparesis/HTLV-I-associated myelopathy in Europe and in Africa: clinical and epidemiologic aspects. [2019]We review here the epidemiologic and clinical aspects of tropical spastic paraparesis, human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy (TSP/HAM) as observed in Europe and in Africa. Europe is not an endemic region for HTLV-I (seroprevalence in blood donors,
[HTLV-I-associated myelopathy/tropical spastic paraparesis: report of 2 cases diagnosed in Florianópolis, Santa Catarina, Brazil]. [2019]We describe two cases of tropical spastic paraparesis/HTLV-I associated myelopathy, according to the criteria of World Health Organization-1989. These are the first cases diagnosed in Florianópolis (Santa Catarina State-Brazil). One of them had a good response with the treatment with methylprednisolone.
[Tropical spastic paraparesis/HTLV-I associated myelopathy. Report of 2 cases diagnosed in Cuiabá, Mato Grosso, Brazil]. [2019]We describe two cases of tropical spastic paraparesis/HTLV-I associated myelopathy, according to the criteria of World Health Organization-1989. These are the first cases diagnosed in Cuiabá (Mato Grosso State, Brazil). One of them had a good response with the treatment with prednisone.
Lisuride for levodopa-induced complications in Parkinson's disease. [2020]To compare the efficacy and safety of adjuvant lisuride therapy versus placebo in patients with Parkinson's disease, already established on levodopa and suffering from motor complications.
[Tiapride with the horn of saiga tatarica in the treatment of hemifacial spasm]. [2013]Tiapride has been used effectively in the clinic for the treatment of dyskinesias and tic disorders including Tourette syndrome. The purpose of the retrospective study is to evaluate the effectiveness of tiapride with the horn of saiga tatarica in treatment of hemifacial spasm.
Critical appraisal of the role of davunetide in the treatment of progressive supranuclear palsy. [2023]Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease characterized by the accumulation of tau protein aggregates in the basal ganglia, brainstem and cerebral cortex leading to rapid disease progression and death. The neurofibrillary tangles that define the neuropathology of PSP are comprised of aggregated 4R tau and show a well-defined distribution. Classically, PSP is diagnosed by symptoms that include progressive gait disturbance, early falls, vertical ophthalmoparesis, akinetic-rigid features, prominent bulbar dysfunction and fronto-subcortical dementia. There are currently no effective therapies for the treatment of this rapidly degenerating and debilitating disease. Davunetide is a novel neuroprotective peptide that is thought to impact neuronal integrity and cell survival through the stabilization of microtubules. Preclinical activity in models of tauopathy has been translated to clinical studies, demonstrating pharmacologic activity that has supported further development. Davunetide's efficacy and tolerability are being tested in a placebo-controlled study in PSP patients, making it the most advanced drug candidate in this indication. This review examines the disease characteristics of PSP, the rationale for treating PSP with davunetide and assesses some of the challenges of clinical trials in this patient population.
Tropical spastic paraparesis treated with Combivir (lamivudine-zidovudine). [2013]Tropical spastic paraparesis (TSP) or human T-cell leukemia virus-type 1 (HTLV-I)-associated myelopathy is caused by human T-lymphotropic virus type 1. It is a slow, progressive spastic paraparesis with significant morbidity and causing profound repercussions on quality of life. No therapies have been found to persistently improve the outcome in these patients. We present a patient with HTLV-1-associated myelopathy/TSP (HAM/TSP) who was treated with Combivir (lamivudine-zidovudine, GlaxoSmithKline, London, UK). She was walker-dependent for several years but, soon after treatment with lamivudine-zidovudine, was able to walk using only a cane. The role of lamivudine-zidovudine should be investigated further in this patient population.
Teriflunomide: a review of its use in relapsing multiple sclerosis. [2021]Teriflunomide (Aubagio™) is the main active metabolite of leflunomide, an established disease-modifying anti-rheumatic drug. Teriflunomide is an inhibitor of de novo pyrimidine synthesis, reducing lymphocyte proliferation, amongst other immunomodulatory effects; autoimmunity is believed to be one of the potential mechanisms of disease for multiple sclerosis. Teriflunomide is considered cytostatic but not cytotoxic: it does not affect resting or slowly dividing lymphocytes. This article reviews the available pharmacological properties of oral teriflunomide and its clinical efficacy and tolerability in patients with relapsing multiple sclerosis. While both the 7 and the 14 mg/day dosages are discussed, the 7 mg/day dosage is not approved in the EU. Both dosages are approved in the USA. In phase III trials, teriflunomide 7 or 14 mg/day was consistently demonstrated to be more effective than placebo and as effective as interferon beta-1a in the prevention of relapses in patients with relapsing forms of multiple sclerosis; moreover, teriflunomide 14 mg/day was also consistently shown to be more effective than placebo in prevention of disability progression. Teriflunomide was generally well tolerated in these patients. Long-term, extension data were generally similar to those observed in the shorter-term trials. Teriflunomide is associated with increased liver enzyme levels, and is contraindicated in pregnant patients because of a potential risk of teratogenicity. As an oral treatment, it offers an alternative to the traditional, parenteral, disease-modifying therapies; however, further investigation into the efficacy and/or tolerability differences between teriflunomide and other available oral drugs would be of great use in the placement of this drug. At present, given the relatively limited long-term data, it is difficult to draw definite conclusions with regard to safety; however, as teriflunomide is the main active metabolite of leflunomide, long-term safety data can be extrapolated from the large amount of post-approval data available regarding its parent drug. Oral teriflunomide is a valuable addition to available treatment options for patients with relapsing multiple sclerosis, in particular those patients who prefer an oral drug.
Teriflunomide (Aubagio®) for the treatment of multiple sclerosis. [2021]Teriflunomide (Aubagio®) is a once-daily oral immunomodulatory disease modifying therapy (DMT) presently approved in several regions, including Europe, North America, Latin America and Australia, for the treatment of relapsing forms of multiple sclerosis (RMS; RRMS). The therapeutic mode of action of teriflunomide in MS continues to be investigated. This review summarizes the main efficacy and safety results of the clinical trial program leading to teriflunomide's approval, highlights a number of practical clinical considerations, and overviews its presumed therapeutic mode of action (MOA) based on pharmacokinetic and pharmacodynamic observations and the growing body of teriflunomide-related in vitro, pre-clinical (animal model), and in vivo human studies.
Longitudinal magnetic resonance imaging in progressive supranuclear palsy: A new combined score for clinical trials. [2018]Two recent, randomized, placebo-controlled phase II/III trials (clinicaltrials.gov: NCT01110720, NCT01049399) of davunetide and tideglusib in progressive supranuclear palsy (PSP) generated prospective, 1-year longitudinal datasets of high-resolution T1-weighted three-dimensional MRI.
Real-life outcomes of teriflunomide treatment in patients with relapsing multiple sclerosis: TAURUS-MS observational study. [2022]Teriflunomide is a once-daily oral immunomodulatory agent approved for the treatment of relapsing-remitting multiple sclerosis (MS). We aimed to obtain data on the effectiveness, tolerability, and subject satisfaction with teriflunomide (Aubagio®) under clinical practice conditions in unselected MS patients.
Teriflunomide: Pediatric First Approval. [2021]Teriflunomide (Aubagio®), which was developed by Sanofi, is an oral immunomodulatory agent targeting the mitochondrial enzyme dihydroorotate dehydrogenase and available to adults to treat relapsing-remitting multiple sclerosis (MS). On 18 June 2021, teriflunomide received its first approval in this indication in pediatric patients aged ≥ 10 years in the EU. This article summarizes the milestones in the development of teriflunomide leading to this first pediatric approval for relapsing-remitting MS.
Real-world study of relapsing-remitting multiple sclerosis patients treated with Teriflunomide in Nordic countries: Quality-Of-Life, efficacy, safety and adherence outcomes. [2022]Teriflunomide 14 mg (Aubagio®) is a once-daily, oral drug approved for the treatment of relapsing forms of multiple sclerosis (MS). While the efficacy and safety of teriflunomide have been thoroughly characterised across an extensive clinical program, we were interested in studying performance of the drug with respect to quality-of-life (QoL) outcomes in persons with MS in a real-world setting.