Investigate the Effect(s) of Methotrexate Treatment on Arthritis Disease SeverityPhase 3NCT04483466
Methotrexate Treatment of Arthritis Caused by Chikungunya Virus (MARCH)
A Phase 3 study testing Methotrexate in people with Investigate the Effect(s) of Methotrexate Treatment on Arthritis Disease Severity, run by George Washington University at 1 site in Colombia.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Investigate the Effect(s) of Methotrexate Treatment on Arthritis Disease Severity
- What is being tested?
- Methotrexate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 1 siteColombia
- Study dates
- 18 Jul 2023to 30 Aug 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of signed and dated informed consent form.
- Stated willingness to comply with all study procedures and availability for the duration of the study.
- Male or female, aged >18 years
- Ability to take oral medication and be willing to adhere to the methotrexate regimen
- For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 3 months after the end of methotrexate administration.
- For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner.
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- Have a diagnosis of CHIKV by CHIKV IgM or IgG antibody.
- The disease duration should be greater than 3 months (based on onset of symptoms).
- Screen laboratory tests must meet the following criteria: Hemoglobin ≥ 9 g/dL, WBCs ≥ 3.5 x 109 cells/L, Neutrophils ≥ 1.5 x 109 cells/L, Platelets ≥ 100 x 109 cells/L, serum transaminase levels not exceeding 1.5 times the upper limit of normal, serum creatinine ≤ 1.6 mg/dL, and negative for hepatitis B surface antigen and hepatitis C antibodies.
- Have a chest radiograph at screening that shows no clear evidence of malignancy or active infection.
- Have active moderate arthritis defined as at least 4 tender joints and at least one joint with definite clinical synovitis (swelling). Joints that may be considered in the count include the temporomandibular joints (0-2), sternoclavicular joints (0-2), acromioclavicular joints (0-2), glenohumeral joints (0-2), elbows (0-2), wrists (0-2), metacarpal phalangeal joints (0-10), finger proximal interphalangeal joints (0-10), finger distal interphalangeal joints (0-8), hips (0-2), knees (0-2), ankles (0-2), tarsus/midfoot (0-2), metatarsal phalangeal joints (0-10), toe proximal interphalangeal joints (0-10).
- Status-post complete Covid vaccination defined as at least 2 weeks after complete vaccination series.
Who cannot join
- Pregnancy or lactation
- Known allergic reactions to components of methotrexate or folic acid.
- Treatment with another investigational drug or other intervention within 1 month.
- History of chronic infection such as hepatitis and HIV. Patients with acute infection will have enrollment deferred until the infection resolves.
- Current signs or symptoms of uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic or cerebral disease.
- Patients with a current diagnosis of class III or IV CHF.
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- History of lymphoproliferative disease including lymphoma.
- Overt or laboratory evidence of immunodeficiency syndromes.
- Any opportunistic infections, including but not limited to evidence of active cytomegalovirus, active Pneumocystis carinii, aspergillosis, histoplasmosis or atypical mycobacterium infection, within the previous 6 months at screening visit.
- History of substance abuse (drug or alcohol) within the previous 2 years.
- Intra-articular, soft tissue or intra-muscular corticosteroid injection during the 4 weeks prior to screening.
- History of prior use of methotrexate or biologic therapy.
- Evidence of active infection with fever >38°
- Current use of any other disease modifying arthritis medication including but not limited to sulfasalazine, methotrexate, hydroxychloroquine, leflunomide, or biologics in the previous 2 months. Patients on stable doses of prednisone up to 10 mg per day for at least 4 weeks prior to enrollment may participate. Non-steroidal anti-inflammatories (NSAIDS) and acetaminophen are permitted for pain during the study.
- Hematuria or proteinuria on urinalysis.
- The presence of anti-cyclic citrullinated peptide (Anti-CCP) antibodies >2 times the upper limit of normal.
- For patients who participate in synovial biopsy substudy the following additional exclusion criteria apply:
- 1. Known prior reactions or allergies to local anesthetics or antibiotics (specifically bupivocaine, lidocaine, or cephalexin) 2. Preexisting advanced structural or functional damage to joint of interest such as prior history of trauma requiring orthopedic surgery and hardware placement, and presence of prosthetic devices (artificial joints, pacemakers, other implantable devices) 3. History of diabetes, skin infections (cellulitis), bleeding disorders, deep vein thrombosis, pulmonary embolism, history or active cancer of any kind 4. Use of blood thinners (anticoagulants) 5. History of or current chronic pain syndrome such as fibromyalgia, chronic back pain, migraines, and history of current complex regional pain syndrome, and /or current or past chronic opiate treatment 6. Significant other comorbidities and /or medication use which in physician's clinical judgment may pause procedure or post-procedure complication risk.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Methotrexate Treatment of Arthritis Caused by Chikungunya Virus (MARCH): A Phase III Randomized Controlled Clinical Trial of the Efficacy of Methotrexate Monotherapy in the Treatment of Chronic Arthritis After Chikungunya Infection
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).
Read the detailed description
- 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.
- Being tested
- Methotrexate, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethotrexateDrug
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.
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Treatment with methotrexate | Experimental | 100 participants will be treated with methotrexate Receives: Drug: Methotrexate |
| Placebo methotrexate | Placebo comparator | 50 will receive placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: up to 6 months
Secondary outcomes (2)
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.
Measured: 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
Measured: Up to 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2020
- Study start18 Jul 2023
- Primary completion30 Aug 2027 (estimated)
- Study completion30 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Investigate the Effect(s) of Methotrexate Treatment on Arthritis Disease SeverityStudies 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
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- * 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, any patient may elect to stop taking the study drug or transition to open label active treatment group for the following six months if non-responder.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- George Washington University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Aileen Y Chang, George Washington University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04483466
- Sponsor's protocol ID
- Chang_MARCH_JUNE2020
- Status last verified
- Dec 2025
- First submitted
- 23 Jun 2020
- Last updated
- 11 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Methotrexate Treatment of Arthritis Caused by Chikungunya Virus (MARCH): A Phase III Randomized Controlled Clinical Trial of the Efficacy of Methotrexate Monotherapy in the Treatment of Chronic Arthritis After Chikungunya Infection
- ClinicalTrials.gov ID
- NCT04483466
- Acronym / sponsor ID
- Chang_MARCH_JUNE2020
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- George Washington UniversityUniversity, hospital or other
- Study start
- 18 Jul 2023 (actual)
- Primary completion
- 30 Aug 2027 (estimated)
- Study completion
- 30 Aug 2027 (estimated)
- First posted
- 23 Jul 2020 (actual)
- 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.
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).
Detailed description
- 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- * 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, any patient may elect to stop taking the study drug or transition to open label active treatment group for the following six months if non-responder.
| Arm | Type | Receives |
|---|---|---|
| Treatment with methotrexate | Experimental | Drug: Methotrexate100 participants will be treated with methotrexate |
| Placebo methotrexate | Placebo comparator | Drug: Placebo50 will receive placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Provision of signed and dated informed consent form.
- Stated willingness to comply with all study procedures and availability for the duration of the study.
- Male or female, aged >18 years
- Ability to take oral medication and be willing to adhere to the methotrexate regimen
- For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 3 months after the end of methotrexate administration.
Key exclusion criteria (18 listed)
- Pregnancy or lactation
- Known allergic reactions to components of methotrexate or folic acid.
- Treatment with another investigational drug or other intervention within 1 month.
- History of chronic infection such as hepatitis and HIV. Patients with acute infection will have enrollment deferred until the infection resolves.
- Current signs or symptoms of uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic or cerebral disease.
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 |
|---|---|---|
| MethotrexateMethotrexate 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. | Drug | Treatment with methotrexate |
| PlaceboPlacebo | Drug | Placebo methotrexate |
Primary outcome
Efficacy of oral methotrexate treatment versus placebo for 6 months in chronic CHIKV arthritis.
Time frame: up to 6 months
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
2 secondary outcomes
Inflammation in the synovial tissue measured by synovial inflammatory cell infiltration
Time frame: Up to 6 weeks
Inflammatory cytokine levels in synovial tissue
Time frame: Up to 6 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2025.
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Methotrexate in people with Investigate the Effect(s) of Methotrexate Treatment on Arthritis Disease Severity, run by George Washington University at 1 site in Colombia.
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 12 inclusion and 18 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: under way, not looking for participants, as of the sponsor's last update on 11 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Colombia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Efficacy of oral methotrexate treatment versus placebo for 6 months in chronic CHIKV arthritis. (time frame: up to 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Dec 2025.