Chikungunya Arthritis in the Americas

NCT02463968 | Completed

• 1 other identifier: 20150352
• Study Type: observational
• Target: 50
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Chikungunya; Arthritis

Outcome Measures

Primary Outcomes (1)

• Presence of chikungunya virus in the synovial fluid of chronic arthritis patients

  Assess the joint for persistence of the chikungunya virus

  Participants will be followed for the duration of a clinic visit which has an expected average time of 1-2 hours

Secondary Outcomes (2)

• Disease Severity Measured by Disease Activity Score-28 Validated Composite Measure

  Participants will be followed for the duration of a clinic visit which has an expected average time of 1-2 hours

• Inflammatory Cytokine Levels

  Participants will be followed for the duration of a clinic visit which has an expected average time of 1-2 hours

Study Arms (3)

CHRONIC CHIKUNGUNYA

Twenty participants with chronic chikungunya defined as continued knee joint effusion at least three months after diagnosis of chikungunya will be enrolled in the study.

Procedure: Venipuncture for blood draw; Procedure: Arthrocentesis for synovial fluid draw

ACUTE CHIKUNGUNYA

Ten participants with acute chikungunya defined as clinical symptoms of chikungunya with acute fever and joint pain within 10 days the onset of symptoms.

Procedure: Venipuncture for blood draw

HEALTHY CONTROLS

Five healthy controls will have only blood drawn once.

Procedure: Venipuncture for blood draw

Interventions

Venipuncture for blood draw PROCEDURE

Samples will include blood. Blood samples will be collected via venipuncture.This is a part of standard of care of new new onset joint effusion and is not a novel intervention.

ACUTE CHIKUNGUNYA; CHRONIC CHIKUNGUNYA; HEALTHY CONTROLS

Arthrocentesis for synovial fluid draw PROCEDURE

Samples will include joint fluid analysis in participants with a knee effusion. Synovial fluid will be drawn via arthrocentesis under sterile conditions. This is a part of standard of care of new new onset joint effusion and is not a novel intervention.

CHRONIC CHIKUNGUNYA

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients living in Baranquilla, Colombia during the study period.

You may qualify if:

• There will be three cohorts of patients.
• Cohort 1 Chronic chikungunya: Twenty participants with chronic chikungunya with knee effusion defined as continued knee joint effusion at least three months after diagnosis of chikungunya.
• Cohort 2 Acute chikungunya: Ten participants with acute chikungunya defined as clinical symptoms of chikungunya with acute fever \>38°C and joint pain within 10 days the onset of symptoms without other more likely diagnosis or laboratory confirmed chikungunya.
• Cohort 3 Healthy controls: Five healthy participants will participate that will provide baseline measurements of the cytokine profile and mononuclear cell sample recovery.
• All subjects will be adults ≥18 years old. Cohort 1 participants will only be enrolled in the study if they have a knee effusion at baseline presentation. Laboratory confirmation of chikungunya includes positive viral PCR or positive IgM antibody. All patients will be able to understand and give informed consent in Spanish.

You may not qualify if:

• Participants will be excluded if they have a known bleeding disorders or if they are on warfarin, clopidogrel, and ticagrelor therapy they will be excluded for increased bleeding risk.
• The study will also exclude children, adults unable to give consent, prisoners, and pregnant women.

Sponsors & Collaborators

• George Washington University: lead
• Global Disease Research: collaborator
• US Army Medical Research Institute of Infectious Diseases: collaborator
• Broad Institute of MIT and Harvard: collaborator
• Allied Research Society: collaborator

Related Publications (1)

• Chang AY, Martins KAO, Encinales L, Reid SP, Acuna M, Encinales C, Matranga CB, Pacheco N, Cure C, Shukla B, Ruiz Arteta T, Amdur R, Cazares LH, Gregory M, Ward MD, Porras A, Rico Mendoza A, Dong L, Kenny T, Brueggemann E, Downey LG, Kamalapathy P, Lichtenberger P, Falls O, Simon GL, Bethony JM, Firestein GS. Chikungunya Arthritis Mechanisms in the Americas: A Cross-Sectional Analysis of Chikungunya Arthritis Patients Twenty-Two Months After Infection Demonstrating No Detectable Viral Persistence in Synovial Fluid. Arthritis Rheumatol. 2018 Apr;70(4):585-593. doi: 10.1002/art.40383. Epub 2018 Mar 7.

  PMID: 29266856 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Cohort 1 CHRONIC CHIKUNGUNYA: Blood samples include one cell preparation tube with Sodium Citrate will be collected for cytokine analysis by mesoscale and mass spectrophotometer analyses, one blood RNA tube for PCR and one blood DNA tube for HLA typing. Synovial fluid samples will be drawn for chronic patients with a knee effusion with one CPT and a blood RNA tube. Cohort 2 ACUTE CHIKUNGUNYA: Blood samples include one CPT for evaluation of biomarkers by mass spectrophotometry, two blood RNA tubes drawn for mass spectrophotometry of viral signaling and genomic analysis and one blood DNA tube for genomic analysis. Cohort 3 HEALTHY CONTROLS: Participants will have one blood RNA tube, one blood DNA tube, and one CPT tube drawn as controls for the other measurements.

MeSH Terms

Conditions

Chikungunya Fever; Arthritis

Interventions

Phlebotomy; Blood Specimen Collection; Arthrocentesis

Condition Hierarchy (Ancestors)

Alphavirus Infections; Arbovirus Infections; Vector Borne Diseases; Infections; Mosquito-Borne Diseases; Virus Diseases; Togaviridae Infections; RNA Virus Infections; Joint Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Therapeutics; Surgical Procedures, Operative; Investigative Techniques; Paracentesis

Study Officials

• Aileen Y Chang, MD MSPH

  George Washington University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: May 29, 2015
• First Posted: June 4, 2015
• Study Start: August 27, 2016
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2017
• Last Updated: June 27, 2017

Record last verified: 2017-06