Methotrexate treatment of Arthritis caused by Chikungunya virus (MARCH): A randomized controlled trial of methotrexate versus placebo in the treatment of chronic arthritis after chikungunya infection

甲氨蝶呤治疗基孔肯雅病毒引起的关节炎（三月）：甲氨蝶呤与安慰剂治疗基孔肯雅病毒感染后慢性关节炎的随机对照试验

• 批准号: 10444183
• 负责人: Aileen Chang
• 金额: $ 158.9万
• 依托单位: GEORGE WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10444183
• 关键词: ATAC-seq; Affect; Aftercare; Alphavirus; American; Arthritis; Autoimmune Process; B-Lymphocytes; Biopsy; Biopsy Specimen; California; Cell Lineage; Chikungunya virus; Chronic; Clinical; Colombia; Culicidae; Degenerative polyarthritis; Disease; Disease Outbreaks; Dose; Evaluation; Evidence based treatment; Folic Acid; Gene Expression; Goals; Guidelines; Immune; Immunoassay; Immunohistochemistry; Infection; Infiltration; Inflammatory; Janus kinase; Leukocytes; Measures; Mediating; Methotrexate; Oral; Outcome; Pain; Pathogenicity; Pathologic; Patient Outcomes Assessments; Patients; Persons; Pharmaceutical Preparations; Placebos; Proteins; Quality of life; Randomized; Randomized Controlled Trials; Recommendation; Reporting; Rheumatoid Arthritis; Rheumatology; Role; Severity of illness; Synovial Fluid; Synovitis; T-Cell Activation; T-Lymphocyte; Therapeutic; Tissue Sample; Tissues; United States; Universities; Viral; Viral Arthritis; Work; arm; chemokine; chikungunya; chikungunya infection; college; cytokine; disability; evidence base; follow-up; macrophage; novel; open label; patient subsets; primary endpoint; randomized placebo controlled trial; response; secondary endpoint; single-cell RNA sequencing; standard care; therapeutic target; therapeutically effective; treatment guidelines

ABSTRACT Chikungunya virus (CHIKV) is an alphavirus spread by mosquitos that causes persistent arthritis in approximately 25% of people two years after initial infection. There is currently no standard evidence-based treatment for CHIKV chronic arthritis. The French guidelines suggest the use of methotrexate in the treatment of chronic CHIKV arthritis however there are no randomized placebo-controlled trials of methotrexate to support this recommendation. Our long-term goal is to guide the evidence-based treatment of CHIKV arthritis. The main goal of this proposal is to determine the efficacy and histopathologic effects of 6 months of methotrexate (n=100) versus placebo (n=50) on synovitis in chronic CHIKV arthritis in Colombia in a randomized controlled trial. Our central hypothesis is that methotrexate will significantly decrease chronic CHIKV arthritis disease severity compared to placebo and suppress leukocyte accumulation and inflammatory cytokine expression in synovial tissue. This hypothesis will be evaluated in 2 specific aims. In Aim 1, we will determine the efficacy of oral methotrexate treatment versus placebo for 6 months in chronic CHIKV arthritis. In Aim 2, we will determine the effect of methotrexate on synovial inflammation by obtaining synovial biopsy samples before and during treatment. Rationale: This work will define the role and mechanism of methotrexate in the treatment of chronic CHIKV arthritis with the goal of advancing the field towards an evidence-based standard treatment. The potential broader impact of this work is the potential identification of the pathologic mechanism of chronic viral arthritis and a possible therapeutic option.

摘要