ChikungunyaNCT02463968
Chikungunya Arthritis in the Americas
An observational study of Chikungunya and Arthritis, run by George Washington University.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Chikungunya, Arthritis
- What is being tested?
- Venipuncture for blood draw and Arthrocentesis for synovial fluid draw
- Type of treatment
- Surgery or procedure
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- 27 Aug 2016to Jun 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients living in Baranquilla, Colombia during the study period.
Who may be able to join
- 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.
Who cannot join
- 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.
About this study
Official title: A Pilot Study of the Pathogenesis of Chikungunya Arthritis in the Americas
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.
Read the detailed description
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.
- Conditions
- Chikungunya, Arthritis
- Being tested
- Venipuncture for blood draw, Arthrocentesis for synovial fluid draw
- Medical subject headings
- Chikungunya Fever, Arthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Venipuncture for blood drawProcedure or surgery
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.
Arthrocentesis for synovial fluid drawProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Procedure: Venipuncture for blood draw | |
| HEALTHY CONTROLS | Five healthy controls will have only blood drawn once. Receives: Procedure: Venipuncture for blood draw |
What is being measured
The primary outcome is the main question the study is designed to answer.
Presence of chikungunya virus in the synovial fluid of chronic arthritis patients
Assess the joint for persistence of the chikungunya virus
Measured: 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
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.
Measured: Participants will be followed for the duration of a clinic visit which has an expected average time of 1-2 hours
Inflammatory Cytokine Levels
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.
Measured: Participants will be followed for the duration of a clinic visit which has an expected average time of 1-2 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2015 (estimated)
- Study start27 Aug 2016
- Primary completionJun 2017
- Study completionJun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ChikungunyaStudies of the same condition, open and under way.
- More trials run by George Washington UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- George Washington University
- Sponsor type
- University, hospital or other
- Collaborators
- Global Disease Research, US Army Medical Research Institute of Infectious Diseases, Broad Institute of MIT and Harvard, Allied Research Society
- Responsible party
- Principal investigator, Aileen Chang, George Washington University
- Investigators
- Aileen Y Chang, MD MSPH, Principal investigator, George Washington University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02463968
- Sponsor's protocol ID
- 20150352
- Status last verified
- Jun 2017
- First submitted
- 29 May 2015
- Last updated
- 27 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 29266856
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of the Pathogenesis of Chikungunya Arthritis in the Americas
- ClinicalTrials.gov ID
- NCT02463968
- Acronym / sponsor ID
- 20150352
- Conditions
- Chikungunya, Arthritis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- George Washington UniversityUniversity, hospital or other
- Collaborators
- Global Disease Research, US Army Medical Research Institute of Infectious Diseases, Broad Institute of MIT and Harvard, Allied Research Society
- Study start
- 27 Aug 2016 (actual)
- Primary completion
- Jun 2017 (actual)
- Study completion
- Jun 2017 (actual)
- First posted
- 4 Jun 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 description
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.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| CHRONIC CHIKUNGUNYA | – | Procedure: Venipuncture for blood draw, Procedure: Arthrocentesis for synovial fluid drawTwenty participants with chronic chikungunya defined as continued knee joint effusion at least three months after diagnosis of chikungunya will be enrolled in the study. |
| ACUTE CHIKUNGUNYA | – | Procedure: Venipuncture for blood drawTen participants with acute chikungunya defined as clinical symptoms of chikungunya with acute fever and joint pain within 10 days the onset of symptoms. |
| HEALTHY CONTROLS | – | Procedure: Venipuncture for blood drawFive healthy controls will have only blood drawn once. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients living in Baranquilla, Colombia during the study period.
Key inclusion criteria (5 listed)
- There will be three cohorts of patients.
- 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.
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Venipuncture for blood drawSamples 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. | Procedure or surgery | ACUTE CHIKUNGUNYA, CHRONIC CHIKUNGUNYA, HEALTHY CONTROLS |
| Arthrocentesis for synovial fluid drawSamples 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. | Procedure or surgery | CHRONIC CHIKUNGUNYA |
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
2 secondary outcomes
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2017.
- Derived from this study: PubMed 29266856Chang 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Aileen Y Chang, MD MSPH principal investigator
George Washington University
Questions about this trial
What is this clinical trial studying?
An observational study of Chikungunya and Arthritis, run by George Washington University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02463968, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2017.