HTLV-1 Infection, HTLV I Associated Myelopathies, HTLV I Associated T Cell Leukemia Lymphoma, Neuritis
Conditions
Keywords
HTLV-1, Dolutegravir, Tenofovir, Treatment, proviral load
Brief summary
This phase 2b, open-label, randomized controlled trial evaluates the efficacy and safety of dolutegravir (DTG) alone versus dolutegravir combined with tenofovir disoproxil fumarate (TDF) in individuals with HTLV-1 infection and associated clinical manifestations. The primary objective is to compare changes in HTLV-1 proviral load at 24 and 48 weeks. Secondary outcomes include clinical, functional, immunological, and quality-of-life measures.
Detailed description
Human T-lymphotropic virus type 1 (HTLV-1) infection is a neglected condition associated with severe neurological and hematological diseases, including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Currently, no effective antiviral therapy exists. Preclinical and clinical data suggest that integrase inhibitors such as dolutegravir may reduce HTLV-1 proviral load. Additionally, combination therapy with tenofovir may enhance antiviral activity. This study builds on prior pilot data demonstrating partial virological response to DTG. Participants will be randomized (1:1) to receive DTG alone or DTG plus TDF for 48 weeks. Outcomes will include virological, immunological, clinical, and patient-reported measures. The study aims to provide evidence for therapeutic strategies targeting HTLV-1.
Interventions
COMBINATION_PRODUCTCombination of Dolutegravir + Tenofovir DF for treatment of HTLV-1 infection
In a previous study Dolutegravir was able to reduce HTLV-1 proviral load, but a few patients did not respond to therapy. We intend to use a combination of Dolutegravir + TDF to improve the response rate. There is no previous evidence on the use of such combination for treating HTLV-1 infection.
Active comparator will be DTG, 50 mg/day
Sponsors
Carlos Brites
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Health professionals who will evaluate patient´s neuro-functional performance will be blinded on treatment arm
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age equal or higher than 18 years * Confirmed HTLV-1 infection * Clinical manifestation atributable to HTLV-1 * Ability to provide written informed consent
Exclusion criteria
* Active HIV, HCV (RNA+), or HBV (HBsAg+) infection * Active tuberculosis * Recent corticosteroid use * Renal impairment (CrCl \<50 mL/min) * Autoimmune diseases * Wheelchair-bound individuals * Active malignancy (except ATLL) * Substance abuse interfering with adherence * Any condition compromising safety
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HTLV-1 Proviral Load | From baseline to the end of treatment at 48 weeks | Measurement of HTLV-1 Proviral Load by RT-PCR. Results will be expressed as copies/ml of whole blood |
| Changes in Pain intensity (DN4 doleur scale) | Baeline, 24 and 48 weeks | Change in intensity of pain measured by DN4 doleur scale (0 to 10, with values \>4 indicating neuropathic pain) |
| Changes in Spasticity | BL, 24 and 48 weeks | Changes in limbs spasticity, as measured by Ashworth scale. The Ashworth Scale uses a simple ordinal scale ranging from 0 to 4, where the highest values mean increased spasticity |
| Changes in muscle strenght | BL, 24 and 48 weeks | Evaluation of muscle strenght by Kendall Muscle Grading system (Kendal scale), which ranges from 0 to 10, with highest values indicating better muscle strenght |
| Changes in motor score scales | BL, 24, 48 weeks | Evaluation of changes in motor performance using the lower extremity motor score (LEMS) is a subscale of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) that assesses lower extremity muscle strength.The score range is 0-5 for each of 5 key muscles (hip flexors, knee extensors, ankle dorsi-flexors, long toe extensors and ankle plantar flexors) of each leg, with a maximum score of 50 (the lower values indicates worse motor function) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Nocturia frequency | Baseline, 24 and 48 weeks | Nocturia frequency across the study |
| Cytokines levels | BL, 24 and 48 weeks | Measurement of levels of (Tumon Necrosis Factor-Alpha) TNF-alpha, IL-6, IL-2, IL-4, IL-10, Interferon γ-induced Protein (IP-10), Gamma-Interferon (Gamma-IFN), in picogram/cubic milimiter. Values may varies from undetectable levels to any detectable concentration, expressed in pg/mm3. |
| RAND 36-Item Health Survey | Baseline and at 48 weeks | The RAND Corporation Health-Related Quality of Life (RAND-36) domains are scored on a 0 to 100 range, so that a high score defines a more favorable health-related quality of life (HRQoL). The scale measure several domains of HRQoL. |
Countries
Brazil
Contacts
CONTACTCarlos Brites, MD, PhD
CONTACTEstela Luz
PRINCIPAL_INVESTIGATORCarlos Brites, MD, PhD
Hospital Universitário Professor Edgard Santos, Federal University of Bahia
Outcome results
None listed