Clinical Trial: Chikungunya Arthritis in the Americas

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Observational

Official Title: A Pilot Study of the Pathogenesis of Chikungunya Arthritis in the Americas

Brief Summary: Chikungunya is a mosquito-borne viral illness that leads to chronic joint pain in approximately one half of patients. The mechanisms leading to long term arthritis in humans has not been well established. There is some evidence from animal studies that activated macrophages with persistent viral infection may play a role in chronic arthritis however these mechanisms have not yet been identified in humans. It is hypothesized that activated macrophages harboring persistent active chikungunya virus are responsible for chronic arthritis and joint pain in patients. The focus of this proposal is to evaluate synovial fluid and blood for direct viral persistence and activated macrophages that may clarify the mechanism of inflammatory injury. The results of this study will be directly applicable to tailoring trials of therapeutics.

Detailed Summary: Chikungunya is rapidly spreading throughout the Americas and causes debilitating chronic arthritis in approximately one fourth of patients. There is currently no standard treatment for chikungunya arthritis, and the mechanisms leading to this chronic arthritis are unclear. Further characterization of the disease pathophysiology is needed in order to guide evaluation of potential therapeutics. It is hypothesized that chronic chikungunya arthritis is due to persistence of active virus in the synovial fluid where macrophages serve as a viral reservoir. The predominance of activated macrophages in persistently infected tissue and the presence of viral genome within these macrophages in non-human primates makes our hypothesis plausible. To test this hypothesis, this study has three Specific Aims. Aim 1, describe host characteristics affect susceptibility to severe or persistent arthritis. Aim 2, determine if chikungunya virus persists in synovial fluid and synovial fluid macrophages in humans as shown in non-human primates. Aim 3, investigate how these macrophages may be activated and modulated by cytokines. To date, these pathophysiologic factors have not been well characterized in humans. Information gained from this study can directly lead to recommendations for the further evaluation of antiviral versus immune modulating medications.
Sponsor: George Washington University

Current Primary Outcome: Presence of chikungunya virus in the synovial fluid of chronic arthritis patients [ Time Frame: Participants will be followed for the duration of a clinic visit which has an expected average time of 1-2 hours ]

Assess the joint for persistence of the chikungunya virus


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Disease Severity Measured by Disease Activity Score-28 Validated Composite Measure [ Time Frame: Participants will be followed for the duration of a clinic visit which has an expected average time of 1-2 hours ]
    Disease Severity Measured by Disease Activity Score-28 Validated Survey that is a series of questions about disease severity that gives a composite score for arthritis severity and C-reactive protein level measured in mg/L.
  • Inflammatory Cytokine Levels [ Time Frame: Participants will be followed for the duration of a clinic visit which has an expected average time of 1-2 hours ]
    Inflammatory cytokines such as IL-10, IL-6, GM-CSF, TNF, IL-2, IL-4, and IL-13 in units of pg/ml will be assessed and compared between acute and chronic patients.


Original Secondary Outcome:

  • Disease Severity Measured by Disease Activity Score-28 Validated Survey and C-reactive protein level. [ Time Frame: Participants will be followed for the duration of a clinic visit which has an expected average time of 1-2 hours ]
    Disease Severity Measured by Disease Activity Score-28 Validated Survey that is a series of questions about disease severity that gives a score for arthritis severity and C-reactive protein level measured in mg/L.
  • Inflammatory Cytokine Levels [ Time Frame: Participants will be followed for the duration of a clinic visit which has an expected average time of 1-2 hours ]
    Inflammatory cytokines such as IL-10, IL-6, GM-CSF, TNF, IL-2, IL-4, and IL-13 in units of pg/ml will be assessed and compared between acute and chronic patients.


Information By: George Washington University

Dates:
Date Received: May 29, 2015
Date Started: July 2016
Date Completion: June 2017
Last Updated: May 10, 2016
Last Verified: May 2016