MARCH is the first randomized, double-blind, placebo-controlled evaluation of the efficacy and pathologic mechanism determined by synovial biopsy of 6 months of methotrexate (n=100) versus placebo (n=50) therapy for chronic chikungunya (CHIKV) arthritis in Colombia with the option for open-label use of the medication for up to one year for all participants. Our central hypothesis is that methotrexate will significantly decrease chronic CHIKV arthritis disease severity compared to placebo via suppression of leukocyte accumulation in synovial tissue and decreased expression of inflammatory cytokines from synovial macrophages and fibroblast-like synoviocytes (FLS).
* In the treatment group, participants will receive methotrexate 15mg by mouth/week with optional for increase up to 20mg/week in non-responders and folic acid 1mg by mouth daily for six months in Phase I. * In the control group, participants will receive placebo methotrexate tablets by mouth/week with faux increase optional in non-responders and folic acid 1mg by mouth daily for six months in Phase I. * In Phase II, patients may elect to stop taking the study drug or in those without clinical remission transition to open label active treatment group for the following six months.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
150
Methotrexate is vibrant yellow-orange colored powder with physical properties of near insolubility in water formulated into methotrexate tablets containing an amount of methotrexate sodium equivalent to 2.5 mg of methotrexate and are round, convex, and yellow. The chemical name is N-\[4-\[\[(2,4-diamino-6pteridinyl)methyl\]methyl amino\]benzoyl\]-L-glutamic acid. Methotrexate is an anti-metabolite that is a folate antagonist that inhibits lymphocyte proliferation and functions as an immunosuppressant in arthritis.
Placebo
Clinica de la Costa
Barranquilla, Colombia
Efficacy of oral methotrexate treatment versus placebo for 6 months in chronic CHIKV arthritis.
An improvement in the Disease Activity Score-28 response. The DAS-28 is a composite measure including a tender and swollen joint joint of 28 joints, patient reported disease severity measures, and the c-reactive protein
Time frame: up to 6 months
Inflammation in the synovial tissue measured by synovial inflammatory cell infiltration
The investigators hypothesize that treatment with methotrexate versus placebo will decrease synovial macrophage and T-cell accumulation.
Time frame: Up to 6 weeks
Inflammatory cytokine levels in synovial tissue
The investigators hypothesize that treatment with methotrexate versus placebo will dampen production of pathogenic cytokines like with TNF, IL-6, and MCP-1
Time frame: Up to 6 weeks
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.