Dolutegravir Versus Dolutegravir in Combination With Tenofovir for the Treatment of HTLV-1 Infection (DOT-H): an Open-label, Randomized, Controlled Study.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 146
- 试验地点
- 1
- 主要终点
- HTLV-1 Proviral Load
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
Health professionals who will evaluate patient´s neuro-functional performance will be blinded on treatment arm
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age equal or higher than 18 years
- •Confirmed HTLV-1 infection
- •Clinical manifestation atributable to HTLV-1
- •Ability to provide written informed consent
排除标准
- •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
研究组 & 干预措施
Combination therapy
Daily Dolutegravir 50 mg Daily Tenofovir 300 mg
干预措施: Combination of Dolutegravir + Tenofovir DF for treatment of HTLV-1 infection (Combination Product)
Dolutegravir
Dolutegravir 50 mg p.o. daily
干预措施: Dolutegravir (DTG) (Drug)
结局指标
主要结局
HTLV-1 Proviral Load
时间窗: 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)
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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)
次要结局
- Nocturia frequency(Baseline, 24 and 48 weeks)
- Cytokines levels(BL, 24 and 48 weeks)
- RAND 36-Item Health Survey(Baseline and at 48 weeks)
研究者
Carlos Brites
Full Professor - Infectious Diseases
Fundação Bahiana de Infectologia